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Editorial: CASE REPORT: ACTIVE PROGRESSIVE BASED ON CLINICAL PRACTICE LEARNING (APB-C)

Arturo José Parada Baños M.D. Universidad Nacional de Colombia Faculty of Medicine Department of Obstetrics and Gynecology Bogotá, – Colombia

https://doi.org/10.15446/cr.v3n1.65433 case reports

Clinical case reports date back to 1600 B. or intervention, or describe some event that C., when Egyptian papyri first described inju- is unknown (8). ries or disorders of the head and the back (1). APB-C learning is an apprentice-centered Likewise, cases reported by Hippocrates, 460 strategy that not only considers students as B.C (2), or the first uterus (3) and face trans- apprentices, but also considers any health plants (4) can be found in the literature, as well professional who progressively builds critical, as cases on the recent Zika epidemic and its autonomous, and creative thinking in an open relation to microcephaly (5). All of them have and malleable way, according to the context, greatly contributed to the evolution of medical and based on new research works. It also science during different periods, both in re- includes professionals with an analytical and search and learning processes. resolute capacity to apply this knowledge Case reports can be considered as scientific in a specific way to each new clinical case publications that represent the simplest form received and, with the potential to broaden of research in the clinical area (6); however, their knowledge and experience finding new they are the evidence of what actually happens meanings. In the context of APB-C learning, in each case. That its usefulness is purely a clinical case report represents a situation investigative is debatable. Case reports have that encourages knowledge, because it not a low profile in relation to the classification of only seeks to solve a problem, but also is, other scientific works, but their contribution to sometimes, the tip of the iceberg for new the understanding of history (1), meaningful knowledge. learning of medicine and a more humanized When the author of a clinical case report view of health care is evident (7). incorporates new knowledge into the cogni- Regardless of the current discussion on tive structure of the professionals who read the hierarchical place of case reports as a it, a meaningful learning process arises, in scientific evidence, it is clear that it has always which each reader gives a personal meaning been present in medical literature, not only to the new acquired knowledge. This way, because of its scientific value, but because relationships with their cognitive structure are it has always been a part of medical learning. established and new theoretical and method- The medicine learning process has evolved, ological elements (9) for teaching-learning moving from positivist and behaviorist the- processes of future research appear. oretical strategies to the current cognitive, One of the most relevant contributions of constructivist and socioconstructivist learning case reports, and the reason why they are still processes. These approaches have allowed an valid today, is the cognitive dynamics generat- active progressive based on clinical practice ed when meaning is given to new knowledge, (APB-C) learning, leaving passive knowledge since it could be integrated or diverge from acquisition processes behind and fostering previous knowledge about a specific topic or active, progressive, participatory and integra- pathology. This active and progressive dynamic tive processes for logical and constructive motivates new ventures in scientific research reasoning based on each clinical case. Cases or learning processes in medicine. are the essence of clinical medicine, even Case reports have been proposed as a more when they report a new disease, are gateway for undergraduate and graduate stu- rare and little known, show a new treatment dents, as well as for professors and research- case report: active progressive based on clinical practice learning (apb-c)

ers, to take their first steps into the world of REFERENCES medical literature. This position is not entirely shared by the author of this editorial, since 1. Nissen T, Wynn R. The history of the case re- case reports of all kinds have been produced port: a selective review. JRSM Open. 2014;5 throughout history, and have been submitted by (4):2054270414523410. doi: http://doi.org/b8fd. new professionals or experts and researchers 2. Abu Kasim NH, abdullah BJJ, Manikam J. of medical science who allow themselves to The current status of the case report: Terminal or be astonished by new knowledge and want viable?. Biomed Imaging Interv J. 2009;5(1):e4. doi: http://doi.org/bhpnr2. to share it. 3. Fageeh W, Raffa H, Jabbad H. Transplanta- The ability to recognize that which gener- tion of the human uterus. Int J Gynaecol Obstet. ates new meaning as learning is what allows 2002;76(3):245-51. many authors to detect a case to report and 4. Siemionow M, Papay F, Alam D, Bernard S, to share it, leaving aside the amount of ex- Djohan R, Gordon C, et al. Near-total human perience they have. If a case is significant face transplantation for a severely disfigured patient enough for an author, it might be significant in the USA. The Lancet. 2009;374(9685):203-9. for others as well. Then a literature review is doi: http://doi.org/cznvb8. initiated, although few cases out of hundreds 5. Mlakar J, Korva M, Tul N, Popović M, Pol- are actually published; what is meaningful jšak-Prijatelj M, Mraz J, et al. Zika Virus and new for an author, may not be for other Associated with Microcephaly. N Engl J Med. professionals. 2016;374:951-8. doi: http://doi.org/f8cm38. 6. Delgado-Ramírez, MB. What is the value of Historically, this type of articles have shown continuing to publish case reports? Rev Colomb a complete picture of clinical practice, which Anestesiol. 2017 [cited May 20 2017];45(S1):1- evidences the differential empathic process 3. Available from: https://goo.gl/87BT5Y. between the attending professional and his 7. Agha R, Rosin RD. Time for a new approach to patients, showing the comprehensive knowl- case reports. Int J Surg. 2010;8(5):330-2. doi: edge that is described in the narrative of the http://doi.org/b3trp6. case. Currently, this comprehensiveness in 8. Romaní-Romaní F. Reporte de caso y serie case presentation is increasingly strengthening de casos: una aproximación para el pregrado. due to the CARE guidelines (consensus-based CIMEL Ciencia e Investigación Médica Es- development of guidelines for reporting clinical tudiantil Latinoamericana. 2010 [cited May 18 cases) (10), which allow for greater scientific 2017];15(1):46-51. Visitado el 18 de mayo de validity and a comprehensive and holistic view 2017. Available from: https://goo.gl/x1cuXd. of each case presentation. 9. Ponce V. El aprendizaje significativo en la inves- tigación educativa en Jalisco. Revista Electrónica Writing and analyzing clinical case reports Sinéctica. 2004 [cited May 20 2017];24:21-9. should be part of the APB-C learning strategies Available from: https://goo.gl/. for undergraduate and graduate students, as well 10. Gagnier JJ, Kienle G, Altman DG, Moher as for practicing professionals, additionally to D, Sox H, Riley D, et al. The CARE Guideli- historical, academic and humanistic interest gen- nes: Consensus-based Clinical Case Reporting erated by the cognitive-constructivist processes Guideline Development. Glob Adv Health Med. of meaningful learning and scientific research. 2013;2(5):38-43. doi: http://doi.org/b8fs. Case Reports 2017; 3(1)

https://revistas.unal.edu.co/index.php/care/article/view/58625 ENVENOMATION CAUSED BY THE BITE OF THE SNAKE BOTHRIECHIS SCHLEGELII. REPORT OF TWO CASES IN COLOMBIA

Palabras clave: Bothriechis schlegelii; Mordeduras de serpientes; Coagulación sanguínea; Colombia. Keywords: Bothriechis schlegelii; Snake bites; Blood coagulation; Colombia.

Mario Galofre-Ruiz, MD, MSc Tox Centro de Información de Seguridad sobre Productos Químicos CISPROQUIM Consejo Colombiano de Seguridad Bogotá D.C. – Colombia

Corresponding author [email protected] Phone number.: (057)3157261026 case reports

ABSTRACT brown and black), helps it mimic its surround- ings. It has prehensile tail, and from two to four The bite by snakes of the Bothriechis genus is small superciliar scales, in the way of “eye- common in certain areas of Colombia such as lashes”. It feeds on baby birds, lizards, frogs the Coffee-growing Region. Due to their arbo- and rodents, inhabits tropical forests and corn real habits and defensiveness, these snakes and coffee crops, at altitudes ranging from 0 usually bite farmers in their upper limbs and to 2600 m; the viper reaches the highest alti- face. In Colombia, the incidence of accidents tude in Colombia (2,3). caused by these snakes has not been accu- In the regions in which it inhabits, it is also rately estimated yet because of deficiencies in known as cabeza de candado, granadilla, ví- recording this type of cases, as well as of the bora de tierra fría, víbora de pestañas, ya- ignorance on this reptile by health personnel ruma, veinticuatro, guacamaya, víbora rayo, working in its area of influence. mortiñera, colgadora and grano de oro (these This paper describes two cases of bites by B. are different names to refer to this snake in schlegelii occurred in Colombia during 2015. diverse regions of Latin America) (2,4). The first case is about a 55-year-old man who B. schlegelii extends from southern Mexi- was bitten on the left hand, and subsequent- co, throughout Central America, to the east of ly developed paresthesia and edema until the Venezuela, and in the Pacific through Costa forearm, with no other findings; the patient un- Rica, Panama, El Salvador and Ecuador (5). derwent treatment with polyvalent antivenin from In Colombia, it lives in the Pacific and Ande- Probiol®, with complete resolution of the event. an regions, and in the Western, Central and The second case portrays a 62-year-old man, bi- Eastern Ranges. In addition, it can be found tten on the left hand, presenting with emesis, dia- from the south to the north of the country, on phoresis, edema until shoulder, prolonged clot- the border with the Venezuelan Andes, and is ting times, and no bleeding; the patient required endemic in the coffee region (2). eight vials of polyvalent antivenin from Instituto Until epidemiological week 32 in 2016, 2 Nacional de Salud (National Institute of Health, 791 cases of snakebite accidents were report- Colombia), thereby normalizing clotting times. ed to Sistema Nacional de Vigilancia en Sa- Complete resolution of the event was achieved. lud Pública (National System of Public Health Surveillance), of which 65.6% corresponded INTRODUCTION to Bothrops (6). However, the number of cases related to snakebites of Bothriechis genus The name Bothriechis schlegelii derives from specimens was not certain. the Greek word bothros, which means “pit” and echis, “snake”, referring to the loreal pit CLINICAL CASES that is located between the nostrils and eyes on each side of the face, and also after the Case 1 German zoologist Hermann Schlegel (1). The length of B. schlegelii, also known as Reason for consultation eyelash pit viper, varies between 50 and 120 cm, being females larger than males. The vari- 55-year-old patient, from Pensilvania, Caldas, ety of its colors (emerald or dark green, yellow, who was bitten on the back of the left hand by envenomation caused by the bite of the snake bothriechis schlegelii

a 25 cm, thin, triangular head snake during his Clinical manifestations and physical work in a coffee crop (Figure 1 and 2). The pa- examination tient denies hypertension, diabetes, kidney disease, bleeding disorders or previous surgeries. The patient presented with pain when moving the affected hand, paresthesia and 2cm edema in the right hand, which spread to the left forearm. No fang punctures nor local bleeding were observed (Figure 3).

Fig 1. Specimen of Bothriechis schlegelii which caused this event, in defensive position. Source: Own elaboration based on the data obtained in the study.

Fig 3. Appearance of the bite by Bothriechis schlegelii. Edema in the left hand and part of the forearm is shown. Source: Own elaboration based on the data obtained in the study.

Laboratory tests

Complete blood count, blood urea nitrogen, creatinine and coagulation tests were performed and no alterations were found. Total Fig 2. Head of the specimen. Multiple scales, CPK was not determined. vertical pupil and loreal pit can be seen. Note: The specimen was handed over to Treatment environmental authorities and returned to its natural habitat. First, the patient was administered intravenous Source: Own elaboration based on the data obtained in the study. fluids, analgesia with tramadol, and tetanus case reports

prophylaxis (after confirming normal coagula- 5). He denies hypertension, diabetes, kidney dis- tion tests). Then, he was referred to a nearby ease, bleeding disorders or previous surgeries. hospital where three vials of polyvalent antiven- om Probiol® were administered intravenously; Clinical manifestations and physical afterwards, the patient developed fever, which examination was controlled with acetaminophen. The pain and edema decreased and, finally, he was dis- The patient was admitted with pain in the left charged after two days of observation. hand, edema of 1 cm in the right hand, paresthesia in the left shoulder, emesis and diapho- Case 2 resis (Figure 6).

Reason for consultation Laboratory tests

62-year-old man, from Fresno, Tolima, who was The following tests were performed: unal- bitten on the third finger of the left hand during ag- tered blood count and prolonged prothrom- ricultural work by a thin snake, known in the area bin time, and partial thromboplastin time. To- as “cabeza de candado (head lock)” (Figure 4 and tal CPK was not determined.

Fig 4. Bothriechis schlegelii. Triangular head. Source: Own elaboration based on the data obtained in the study.

Fig 5. Bothriechis schlegelii. Prehensile tail. Note: The specimen was sacrificed before consultation with the attending physician. Source: Own elaboration based on the data obtained in the study. envenomation caused by the bite of the snake bothriechis schlegelii

type proteinase inhibitor, serine proteinases, L-amino acid oxidase and cysteine-rich secre- tory proteins (CRISPs), therefore, its properties are hypotensive, edema-forming, procoagulant, myotoxic, necrotizing and hemorrhagic (7). When dealing with bites by a Bothriech- is snake, assessing the severity of the bite through the clinical grading adapted by Ote- ro is important (8), which also serves to determine the amount of antivenin to use. The grades presented by Otero (8) are: Grade 1, absent, only minimal pain; Grade 2, mild, presence of edema (<4 cm) that com- promises one or two segments of the bitten limb, ecchymosis, scarce bleeding with normal coagulation or incoagulable blood; Grade 3, moderate, with edema (> 4 cm) that com- Fig 6. Appearance of bothriechis schlegelii bite. promises three segments of the bitten limb, Edema in the left hand. blisters, local incoagulable bleeding or pres- Source: Own elaboration based on the data obtained in the study. ence of systemic hemorrhage; Grade 4, severe, presence of edema beyond the bitten limb, necrosis, compartment syndrome, local Treatment hemorrhage with incoagulable blood, systemic hemorrhage (including brain hemorrhage), The patient received intravenous fluids, an- hypotension or shock, disseminated intravas- algesia and six vials of polyvalent antivenin cular coagulation, renal failure and multiple produced by Instituto Nacional de Salud in- organ dysfunction. According to this, the two travenously, without adverse reactions. After cases were considered as mild. finding an alteration in clotting, the patient The symptoms manifested by the patient was given two additional vials of polyvalent in the first case —localized pain and progres- antivenin, for a total of eight, and was referred sive edema— correspond to the initial symp- to a third level hospital level in Ibagué. In the toms caused by the bite of this snake, which referral hospital, the patient’s condition im- in some cases may be accompanied by hem- proved, and coagulation tests were normal orrhagic blisters, itching, bruising and necro- 48 hours after the event; finally, he was dis- sis (9, 10). In Colombia, severe poisoning by charged after 72 hours of observation. Bothrops asper, Bothrops punctatus, Port- hidium nasutum and Bothriechis schlegelii DISCUSSION bite has been characterized and includes local necrosis, systemic and local bleeding, The venom of B. schlegelii consists, mostly, of hypotension and renal failure (11). phospholipase A2, followed by metalloprotein- In the second case, although no marked ases, bradykinin potentiating peptides, Kazal local symptoms were observed, there was a case reports

significant commitment of clotting, which can corticosteroids if they are mild to moderate, or be explained by two reasons: the direct inoc- adrenaline if anaphylactic shock occurs (2,8). ulum of poison inside a blood vessel, and the The polyvalent antivenin produced by Bio- presence of metalloproteinases in the pro- clon Institute of Mexico has also been used to tein composition of the poison, because their treat this type of envenomation; also, it showed concentration in the venom of B. schlegelii that it can reverse the procoagulant effect of (17.7%) is lower compared to that of B. lat- the venom of B. schlegelii, as well as the poly- eralis (55.1%). This specimen has shown a valent serum antivenin produced by Instituto wide range of biological activities, such as Clodomiro Picado in Costa Rica (15). hemorrhagic fibrinogenolytic degradation of components in the extracellular matrix, and CONCLUSIONS activation of prothrombin and factor X, resulting in extensive local tissue damage and sys- Due to the correct classification of the severity temic bleeding (12,13). of envenomation cases, the accurate identifi- cation of the causative specimens, the ad- TREATMENT CONSIDERATIONS equate dose and the quality of the antivenin used, a satisfactory outcome was achieved in Appropriate initial measures for such events both patients. include complete medical history; cardio- B. schlegelii bite produces poisoning, but vascular, respiratory and neurological evalu- this fact is underestimated in Colombia, part- ation; intravenous fluids in a limb other than ly because of the ignorance that health per- the affected one; bite site antisepsis; gastric sonnel have of this snake and because of the protection and oral rest due to the risk of characteristics of their venom. Accurate diag- bleeding; prophylaxis for tetanus with tetanus nosis and specific treatment with polyvalent toxoid when coagulation times are normal or antivenin are crucial to prevent further morbid- normalized after treatment; broad spectrum ity in these patients. antibiotic therapy in case of documented infection, and analgesia with opioids. Non-ste- FUNDING roidal anti-inflammatory drugs should be avoided (14). None declared by the author. Currently, three types of antivenins are available in Colombia: one manufactured by CONFLICT OF INTEREST Instituto Nacional de Salud, one manufactured by Laboratory Probiol® produced in Colom- None declared by the author. bia, and another manufactured by Bioclon In- stitute of Mexico. The first two act against the REFERENCES venom of B. schlegelii and, according to their availability, should be used taking into account 1. Arteaga A, Bustamante L, Guayasamin JM. possible adverse reactions such as anaphy- The amphibians and reptiles of Mindo. Quito: Univer- laxis, serum sickness, acute renal failure or sidad Tecnológica Indoamérica; 2013 [cited 2016 pyrogenic reactions, which are treated with Dec 27]. Available from: https://goo.gl/kGlJ19. envenomation caused by the bite of the snake bothriechis schlegelii

2. Charry H. Aspectos biomédicos del accidente 8. Otero-Patiño R. Epidemiological, clinical and the- Bothrópico. In: Memorias del Primer Simposio rapeutic aspects of Bothrops asper bites. Toxicon. de Toxinología Clínica “César Gómez Villegas”. 2009;54(7):998-1011. http://doi.org/c38pdn. Bogotá: Laboratorios Probiol Ltda. Facultad de 9. Gutiérrez J, Lomonte B. Local tissue damage Medicina, Fundación Universitaria San Martín; induced by Bothrops snake venoms. A review. 2006 [cited 2016 Dec 27]. p. 1-24. Available Mem. Inst. Butantan. 1989;51:211-23. from: https://goo.gl/MIuhQD. 10. Warrell D. Snakebites in Central and South Ame- 3. Vásquez C, Avendaño Ch. Manual para la iden- rica: Epidemiology, Clinical Features, and Clinical tificación, prevención y tratamiento de mordedu- Management. In: Campbell JA, Lamar WW, editors. ras de serpientes venenosas en Centro América, The Venomous Reptiles of the Western Hemisphe- Volumen I: Guatemala. Washington D.C.: Orga- re; Campbell J, Lamar W, editors. Ithaca: Comstock nización Panamericana de la Salud-OPS, Orga- Publishing Associates; 2004. p. 709-61. nización Mundial de la Salud-OMS; 2009. 11. Otero R, Gutiérrez J, Mesa MB, Duque E, 4. Ayerbe-González S, Rodríguez-Buitrago Rodríguez O, Arango JL, et al. Complications JR. Accidente Ofídico Bothrópico. In: Ministerio of Bothrops, Porthidium, and Bothriechis snake- de la Protección Social de Colombia. Guías para bites in Colombia. A clinical and epidemiological el manejo de Urgencias Toxicológicas. Bogotá: study of 39 cases attended in a university hospi- Ministerio de Protección Social de Colombia, tal. Toxicon. 2002;40(8):1107-14. Universidad Nacional de Colombia; 2010 [cited 12. Gutiérrez JM, Rucavado A, Escalante T, 2016 Dec 27]. p 277–80. Available from: ht- Díaz C. Hemorrhage induced by snake venom tps://goo.gl/uXNVsT. metalloproteinases: biochemical and biophysical 5. Toxinology Department, Women’s & Children’s mechanisms involved in microvessel damage. Hospital. Snakebite Management Overview Do- Toxicon. 2005;45(8):997-1011. cument. North Adelaide: State Toxinology Servi- 13. Fox JW, Serrano, SM. Structural considera- ces; 2011. tions of the snake venom metalloproteinases, key 6. León-Núñez LJ. Informe del evento accidente members of the M12 reprolysin family of metallo- ofídico hasta el periodo epidemiológico VIII, Co- proteinases. Toxicon. 2005;45(8):969-85. lombia, 2016. Bogotá: Instituto Nacional de Sa- 14. Alarcón J, Ángel LM, Rojas C. Acciden- lud de Colombia; 2016. te ofídico en pediatría. Revista Gastrohnup. 7. Lomonte B, Escolano J, Fernández J, Sanz 2012;14:S14-S26. L, Angulo Y, Gutiérrez J, et al. Snake venomics 15. Buschek S, Ignjatovic V, Summerhayes R, and antivenomics of the arboreal neotropical pitvi- Lowe R. The effect of different snake venoms pers Bothriechis lateralis and Bothriechis schle- and anti-venoms on thrombin clotting time in hu- gelii. J Proteome Res. 2008;7(6):2445-57. http:// man plasma. Thromb Res. 2012;125(4):e149- doi.org/bs7h73. 52. http://doi.org/dwn8bm. Case Reports 2017; 3(1)

https://doi.org/10.15446/cr.v3n1.58952 THROMBOELASTOGRAPHYGUIDED TRANSFUSION THERAPY IN A PREGNANT PATIENT WITH HEMORRHAGIC DENGUE FEVER HOSPITALIZED IN ICU. CASE REPORT Palabras clave: Dengue hemorrágico; Tromboelastografía; Embarazo Keywords: Severe Dengue; Thrombelastography; Pregnancy

José A. Rojas, MD Daniel Molano-Franco, MD Tito Jiménez, MD Albert Valencia, MD Rafael Leal, MD Pablo Méndez, MD Victor Nieto, MD Diego Hernández, MD Intensive Care Unit – Clínica Universitaria Colombia – Critical Medicine Research Group – Fundación Universitaria Sanitas – Bogotá, D.C. – Colombia

Corresponding author: Daniel Molano-Franco. Clínica Universitaria Colombia – Calle 22b # 66-46, piso 3, Unidad de cuidado intensivo. Bogotá D.C. – Colombia. Phone number: +57 3112263388 case reports

ABSTRACT sponded to severe dengue, and 25 174 to patients under 15 years of age, with a mortality Dengue fever is the biggest public health issue rate of 3.9%. Such figures labeled the country in tropical countries. A significant percentage as an endemic territory for dengue fever in the of patients who suffer from this disease require past years (2). Data on its incidence in obstetric admission to the intensive care unit (ICU) due population are not clear; however, a suscep- to the severity of the clinical picture. This case tibility condition related to the development reports the clinical evolution of an eight-week of infections has been reported, as well as an pregnant woman with dengue fever associated increase in their severity. In addition, growing with thrombocytopenia and leukopenia. The evidence on predisposition to the development patient comes from an endemic area for tropical of activation pictures and severe immune re- diseases, fact that led to diagnose dengue fever sponse has been found, especially in cases of with hemorrhagic characteristics. Plasmodium falciparum and Listeria monocy- During her stay in the ICU, the patient pre- togenes infections, and viral infections such as sented with first trimester bleeding and placen- influenza A(H1N1) (3). tal hematoma. Therefore, and considering the Recently, guided transfusion therapy tech- pregnancy and the risk of loss, the hematological niques, such as thromboelastography, have been function was monitored through thromboelas- implemented in patients with critical illnesses to tography. The transfusion of blood products evaluate the different phases of coagulation and was decided according to the specific findings. clot lysis. The reduction of morbimortality and Controlling and reversing the obstetric bleeding the cost associated with health care, as a result process was possible, the patient condition of the decrease in the number of transfusions, evolved favorably, and she was subsequently have been described as the main advantages of discharged from the ICU. This article reports their use (4). Although reports evidencing the on the usefulness of dynamic monitoring the usefulness of thromboelastography in sepsis (5) hematological function using thromboelastogra- can be found, its clinical applicability in patients phy in patients with hemorrhagic dengue fever with dengue fever infection and hemorrhagic and special conditions such as pregnancy. complications requiring administration of blood products is unknown to date. INTRODUCTION Considering the facts exposed above, this article presents the case of a pregnant patient Dengue fever is a tropical disease character- infected with dengue hemorrhagic fever, treated ized by high fever and bleeding caused by the in a university hospital of Colombia. This patient dengue arbovirus. It is transmitted by the bite of underwent a transfusion therapy through throm- Aedes aegypti, of the flavivirus genus, a species boelastography with the purpose of controlling largely found in territories below 1800 masl. obstetric bleeding and avoiding pregnancy loss. According to the World Health Organization (WHO), dengue fever is the biggest public CASE PRESENTATION health issue in tropical and subtropical countries, accounting for more than 500 000 hospitalizations Patient Information per year, with a mortality rate of 1% (1). In 2012, 54 726 cases of dengue fever were 33-year-old pregnant housewife, born in Bo- reported in Colombia, of which 1 641 corre- gotá D.C. thromboelastography-guided transfusion therapy in a pregnant patient

Clinical findings was confirmed after obtaining positive IgG and IgM tests for dengue fever. 33-year-old woman, with no previous medical-surgical history, and eight weeks into her THERAPEUTIC MANAGEMENT second pregnancy by the time she attends the emergency department. She reported a clinical On the third day of hospitalization and facing picture of five days of repeated intermittent fever an abrupt reduction of platelet count, a platelet of 38.3°C, associated with chills, generalized transfusion was indicated and a thromboelas- myalgias, musculoskeletal, recto-ocular and togram (TbEg) was performed to determine headache pain, as well as nausea, asthenia, the coagulation status. TbEg reported R: 12.5, adynamia and abdominal pain. K: 13.0, alpha: 20.4, MA: 27.2 (Figure 1A). She denies any history of trauma and vaginal Furthermore, a control complete blood count or urinary tract infections. Likewise, she report- taken six hours after the platelet transfusion ed that, by the time of consultation, she was yielded the following results: Hg: 14.4 g/dL, getting prenatal care and that no abnormality Hct: 42.3%, Polys: 50%, Lymphs: 40.1%, plate- had been found. She also reported that seven let count: 20 700 c/mm3. Taking into account days before the consultation she had been in an the risk of miscarriage due to persistent vaginal endemic region for multiple tropical diseases, a bleeding, a transfusion of blood products was place located at 300 masl; further investigation administered again, this time with platelets revealed that she received multiple insect bites and fresh frozen plasma (FFP); phytonadione during the trip. 10mg was initiated intravenously (IV). The control thromboelastograms requested within Calendar and diagnostic evaluation the next 24 hours are shown below (Figure 1 A, B, C and D). Based on clinical findings, a possible dengue virus infection was suspected and paraclini- Monitoring and evolution cal tests were requested for admission (Table 1). Physical examination on admission did not During ICU stay, a positive IgM and IgG se- show any lesion associated with hemorrhagic rum antigen for dengue fever was reported. phenomena such as ecchymosis, petechia or In addition, the evolution of the patient was hematoma. The only abnormal finding developed satisfactory, and no new episodes of bleeding during her stay in the emergency room after occurred. On the sixth day of evolution of the presenting with an episode of acute, sparse disease and with TbEg in the correction phase, and bright genital bleeding. Pelvic examina- the patient was discharged from the ICU with- tion was omitted, and an obstetric ultrasound out complications. Multidisciplinary follow-up was performed, confirming fetal viability and by obstetrics, infectology and psychology was the presence of a retroplacental hematoma of indicated. Seven days after the discharge, an approximately 50%, which could be a sign of obstetric ultrasound was performed, which threatened abortion. Due to the risk of hemor- showed that retroplacental hematoma persisted rhagic complication, the patient was transferred with a 50% decrease of the original size and to the ICU, where the dengue infection diagnosis fetal viability. case reports

Table 1. Hemogram and blood chemistry from admission until day five. Paraclinical exams Leuko- Neutro- Platelet TB DB LDH Hgb/ Hct AST ALT PT PTT cytes phils count (mg/ (mg/ (mg/ dl (%) (U/L) (U/L) (seg) (seg) c/mm3 c/mm3 c/mm3 dl) dl) dl)

1 2500 1800 117000 13.6 41 ------Day 11 46

2 3250 1340 45000 14 41 1022 1172 0.29 0.15 1118 Day (Ct 10) (Ct 26)

11 46 3000 1250 30000 14 42 919 954 ------(Ct 10) (Ct 28) Day 3 (0 hour)

-- -- 20700 14.2 42 ------Day 3 (6 hour)* 11 28

4 4250 2300 42000 13 43 382 457 0.5 0.29 320 Day (Ct 10) (Ct 26)

5 5300 2700 65000 13 40 ------Day

AST: Aspartato transferasa; ALT: Alanino transferasa; BT: Bilirrubina Total; BD: Bilirrubina Directa; c: células; Ct: Control; LDH: Lactato Deshidrogenasa; PT: Tiempo de Protrombina; PTT: Tiempo Parcial de Tromboplastina; Rto: Recuento; Hgb: hemoglobina, Hcto: hematocrito; PT: tiempo protrombina; PTT: tiempo de tromboplastina; LDH: deshidrogenasa láctica.

Source: Own elaboration based on the data obtained in the study.

Figure 1 A. Initial thromboelastogram showing an anticoagulation pattern and deficiency of coagulation factors (prolonged k time, decreased alpha angle, and decreased maximum amplitude). thromboelastography-guided transfusion therapy in a pregnant patient

Figure 1 B. Control thromboelastogram (TbEg) # 1 done after the transfusion of platelets and of 10U FFP (gradual correction in K time values, alpha angle, and maximum amplitude). Figure 1 C. Control TbEg # 2 done after the second transfusion of platelet concentrate. Figure 1 D. Control TbEg # 3 done after the FFP transfusion (correction of K time, alpha angle, and maximum amplitude close to reference values). case reports

DISCUSSION a regional dengue epidemic, without finding associated chromosomal defects (11). The clinical presentation of dengue is broad and Most individuals who are infected and devel- depends on the phases of the disease, which op the disease, evolve to classic dengue fever, range between asymptomatic or febrile cases a self-limited febrile disease that usually does during the febrile phase (0-3 days), severe not represent any complication. Nevertheless, cases of bleeding, shock or organ dysfunction a variable amount of patients develop sponta- during the critical phase (3-6 days), and the neous bleeding, decreased platelet count and resolution of symptoms in the convalescent signs of plasma extravasation; all these mani- phase (>6 days). Recently, a classification of festations define the dengue hemorrhagic fever. this disease was made according to its clinical Hemorrhagic manifestations have been re- presentation to timely identify severe cases and ported in 35-50% of cases, the most common establish proper treatment. Such classification being epistaxis, gingivorrhagia, and gastroin- is based on the presence or absence of warning testinal bleeding (12-13). Despite this trend, signs and severe dengue states characterized some authors, such as Chaudhary et al. (14), by shock, bleeding or organ involvement such consider that there is no association between as myocarditis, hepatitis, encephalitis, and renal hemorrhagic manifestations and platelet count, failure (6). although, this claim has not been confirmed yet The risk of hemorrhagic dengue fever during due to the heterogeneity of patient selection. pregnancy is determined according to the tri- Deep thrombocytopenia may be strongly related mester in which it is contracted, and includes to the severity of dengue in special populations vaginal bleeding, threatened abortion, and such as children and pregnant women, for whom abruptio placentae. In this regard, Carles et it is estimated in terms of major and minor bleed- al. (7) determined an increased preterm de- ings and signs of plasma extravasation. livery rate of 55% in French Guyana, which is Discussions around transfusions, particu- similar to the findings reported by Poli et al. (8). larly about platelets, have been held regarding Restrepo et al. (9) reported an increase in the pregnant women. To date, no information has incidence of threatened abortion and preterm been published that could certainly associate delivery in patients with dengue hemorrhagic abortion with dengue infection during the first fever in Colombia. trimester, whereas an association between the A more recent study reports that 10% of presence of a placental hematoma and the risk cases show hemorrhagic events associat- of miscarriage has been reported in 5 to 17% ed with maternal dengue infection, stressing of losses in patients with hematomas, with an that an association with retroplacental he- OR of 2.18 (1.20-3.67) (15-17). matoma is observed during the first trimester Although multiple etiologic causes of retro- (10). Evidence suggesting that there is no placental hematomas have been found, including relationship between dengue and congen- fetal malformations, corpus luteum insufficiency, ital malformations during the first trimester trauma and perinatal infections such as par- of pregnancy has been compiled. However, vovirus and toxoplasmosis, they have also been in India, Sharma & Gulati (11) have reported reported in infections contracted at the uterine some cases of neural tube defects following and systemic level (18). When considering the thromboelastography-guided transfusion therapy in a pregnant patient

case presented here, it is possible to affirm that only through resting and medical management the placental hematoma was associated with of the viral infection symptoms can be further a systemic viral infection, which worsens due discussed, this report raises the possibility of to the presence of hematological dysfunction including this treatment in the medical practice. with severe thrombocytopenia. The literature does not provide records re- In this context, there is no protocol to deter- garding the assessment of the performance mine whether the correction of coagulopathy and the usefulness of thromboelastography as improves obstetric prognosis and reduces the a dynamic test to define the correctness of co- risk of abortion. In a series of 53 patients, Ba- agulopathy and, specifically, thrombocytopenia surko et al. (10) reported two cases of early in patients with dengue hemorrhagic fever, as abortion due to utero-vaginal bleeding and well as in pregnant patients with dengue fever. five hemorrhagic complications at the time of Its use has been reported in relation to other delivery. Another study by Chotigeat et al. (19) obstetric conditions, such as acute fatty liver made a comparison between patients who were of pregnancy (21), which is another reason to transfused platelets before delivery and patients consider this report as relevant. who were not transfused, finding a reduction of However, this reports also lacks information associated bleeding events in the first group. on other causes of placental hematoma, such Thromboelastography assesses hemostasis as fetal malformations, which were not deter- from a functional point of view, and is represent- mined since the described clinical management ed by the interpretation of the cellular coagu- was selected due to the gestational age of the lation model. Its application in different clinical patient and the acute course of the disease. scenarios, especially in cardiovascular surgery patients and trauma patients, is a proper option CONCLUSION to correct acute hematological alterations and to decrease the unnecessary use of blood prod- Patients with retroplacental hematoma and ucts. (20). It is worth noting that conventional dengue fever infection associated with se- coagulation tests do not allow managing the vere thrombocytopenia are at increased risk underlying coagulation disorder, which often of miscarriage and fetal loss. In consequence, results in unnecessary replacement of blood coagulopathy correction may improve pregnancy components. Thus, thromboelastography allows prognosis. Conventional coagulation tests may physicians to recognize a coagulopathy and, underestimate the risk of coagulopathy and more importantly, to understand the underlying increased bleeding secondary to hematoma. coagulation disorder (20). Thromboelastography may be a useful tool In this case, the alteration was determined for identifying patients at high risk of bleeding at its full extent by using thromboelastography, due to severe thrombocytopenia in cases of which allowed transfusing platelets to correct dengue fever during pregnancy, so its use in this variable and to ensure adequate platelet institutions where this technology is available function, therefore, resolving the vaginal bleed- should be considered. ing. Although determining if this behavior was beneficial to the patient or if the resolution of CONFLICT OF INTERESTS vaginal bleeding and subsequent reabsorption of the hematoma could have been achieved None stated by the authors. case reports

FUNDING epidemics in Tahiti (1989). Bull Soc Pathol Exot. 1991;84(5 Pt 5):513-21. None stated by the authors. 9. Restrepo BN, Isaza DM, Salazar CL, Ra- mírez JL, Upegui GE, Ospina M, et al. Efectos REFERENCES por la infección del virus del dengue sobre el feto y el recién nacido. Biomedica. 2003;23(4):416- 1. World Health Organization. Dengue Haemorrha- 23. http://doi.org/bx5v. gic Fever: early recognition, diagnosis and hos- 10. Basurko C, Carles G, Youssef M, Guindi W. pital management. An audiovisual guide for heal- Maternal and Fetal consequences of dengue fever th-care workers responding to outbreaks. WHO; during pregnancy. Eur J Obstet Gynecol Reprod 2006 [cited Feb 02 2017]. Available from: ht- Biol. 2009;147 (1):29-32. http://doi.org/dvg8hq. tps://goo.gl/Mv8kph. 11. Sharma JB, Gulati N. Potential relationship be- 2. Ministerio de Salud y Protección Social. Circu- tween dengue fever and neural tube defects in a lar 8. Instrucciones para la intensificación de las northern district on India. Int J Gynaecol Obstet. acciones de vigilancia, prevención, atención y 1992;39(4):291-5. http://doi.org/bwzcmf. control del dengue y dengue grave en Colombia. 12. Makroo RN, Raina V, Kumar P, Kanth RK. Bogota, D.C.: MinSalud;2013. Role of platelet transfusion in the management of 3. Kourtis AP, Read JS, Jamieson DJ. Pregnancy dengue patients in a tertiary care hospital. Asian J and infection. N Engl J Med. 2014;370(23):2211- Tranfus Sci. 2007;1(1):4-7. http://doi.org/b7bkqg. 18. http://doi.org/bx5c. 13. Chairulfatah A, Setiabudi D, Agoes R, Cole- 4. Levi M, Hunt BJ. A critical appraisal of point-of- bunder R. Thrombocytopenia and platelet transfu- care coagulation testing in critically ill patients. J sion in dengue haemorrhagic fever and dengue shock Thromb Haemost. 2015;13(11):1960-7. http:// syndrome. WHO Dengue bulletin. 2003;27: 141-3 doi.org/bx5d. 14. Chaudhary R, Khetan D, Sinha S, Sinha P, 5. Zhong S, Zhang C, Hu J, Tang Z. Evaluation of Sonker A, Pandey P, et al. Transfusion support coagulation disorders with thrombelastography to dengue patients in a hospital based blood in patients with sepsis. Zhonghua Wei Zhong transfusion service in north India. Transfus Apheric Bing Ji Jiu Yi Xue. 2016;28(2):153-8. 10.3760/ Sci. 2006;35(3):239-44. http://doi.org/cz5m85. cma.j.issn.2095-4352.2016.02.013. 15. Şükür YE, Göç G, Köse O, Açmaz G, Özmen 6. Ministerio de la Protección Social, Instituto Na- B, Atabekoğlu CS, et al. The effects of subcho- cional de Salud, Organización Panamericana rionic hematoma on pregnancy outcome in pa- de la Salud.. Guía para la atención clínica inte- tients with threatened abortion. J Turk Ger Gynecol gral del paciente con dengue. Bogotá: MinSa- Assoc. 2014;15(4):239-42. http://doi.org/bx5z. lud;2010 [cited Feb 02 2017]. Available from: 16. Soldo V, Cutura N, Zamurovic M. Threatened https://goo.gl/0niJbQ. miscarriage in the first trimester and retrochorial he- 7. Carles G, Peiffer H, Talarmin A. Effects of matomas: sonographic evaluation and significance. dengue fever during pregnancy in French Guia- Clin Exp Obstet Gynecol. 2013;40(4): 548-50. na. Clin Infect Dis. 1999;28(3):637-40. http:// 17. Tuuli MG, Norman SM, Odibo AO, Maco- doi.org/cg8wdr. nes GA, Cahill AG. Perinatal outcomes in wo- 8. Poli L, Chungue E, Soulignac O, Gestas men with subchorionic hematoma: a systema- P, Kuo P, Papouin-Rauzy M. Materno-Fetal tic review and meta-analysis. Obstet Gynecol. Dengue. Apropos o 5 cases observed during the 117(5):1205-12. http://doi.org/bgqbhk. thromboelastography-guided transfusion therapy in a pregnant patient

18. Xiang L, Wei Z, Cao Y. Symptoms of an in- boelastometry for guiding bleeding manage- trauterine hematoma associated with pregnancy ment of the critically ill patient: a systematic complications: a systematic review. PLoS One. review of the literature. Minerva Anestesiol. 2014;9(11):e111676. http://doi.org/bx53. 2014;80(12):1320-35. 19. Chotigeat U, Kalayanaroojs S, Nisalak A. 21. Crochemore T, de Toledo Piza FM, Silva Vertical transmission of dengue infection in Thai E, Corrêa TD. Thromboelastometry-guided he- infants: two case reports. J Med Assoc Thai. mostatic therapy: an efficacious approach to ma- 2003;86 (Suppl 3):S628-32. nage bleeding risk in acute fatty liver of pregnan- 20. Haas T, Görlinger K, Grassetto A, Agos- cy: a case report. J Med Case Rep. 2015;9:202. tini V, Simioni P, Nardi G, et al. Throm- http://doi.org/bx54. Case Reports. 2017; 3(1)

https://doi.org/10.15446/cr.v3n1.59469

STUMP APPENDICITIS IN A 2 YEAR-OLD PATIENT. CASE REPORT AND LITERATURE REVIEW

Palabras clave: Apendicitis; Abdomen agudo; Laparoscopia; Complicaciones posoperatorias. Keywords: Appendicitis; Abdomen, Acute; Laparoscopy; Postoperative complication.

Andrés Guillermo Ramírez, MD Universidad Nacional de Colombia Facultad de Medicina. Pediatric Surgery Service Fundación Hospital de la Misericordia. Bogotá D.C. – Colombia

Fernando Fierro, MD Universidad Nacional de Colombia Facultad de Medicina. Pediatric Surgery Service Fundación Hospital de la Misericordia. Bogotá D.C. – Colombia

Diana Alejandra Holguín, MD Universidad Nacional de Colombia Facultad de Medicina. Pediatric Surgery Service Fundación Hospital de la Misericordia. Bogotá D.C. – Colombia

Mizrahim Méndez, MD Pediatric Surgery Service Fundación Hospital de la Misericordia. Bogotá D.C. – Colombia

Corresponding author: Andrés Ramírez. Fundación HOMI Hospital de la Misericordia. Avenida Caracas No. 1-13. Bogotá D. C., Colombia. Correo electrónico: [email protected] case reports

ABSTRACT lays its diagnosis and treatment, causing morbid complications related to an acute abdomen. Stump appendicitis is a rare cause of acute The clinical picture is very similar to appen- abdomen in the pediatric population, there- dicitis, and it should be suspected in patients fore, it is not suspected frequently. This pa- with a history of appendectomy. There are sev- per presents the case report of a 2-year-old eral diagnostic aids available in case of doubt, child admitted into the emergency room due such as ultrasounds and tomography, which to vomiting, abdominal pain and fever. in some case series have shown good results. On admission, the patient presented with The hypothesis of an increased number of cas- tachypnea, tachycardia, abdominal bloating and es in patients undergoing laparoscopic appen- abdominal tenderness; laboratories showed dectomy generates different opinions and is a leukocytosis, thrombocytosis and an elevat- controversial issue (4, 5, 6, 7). ed C-reactive protein (CPR) levels. Abdominal This paper presents a case report regarding obstruction was considered because of a prior stump appendicitis in a pediatric patient, as well history of peritonitis associated with perforated as a review of the literature. Due to the low inci- appendicitis. However, an emergency laparot- dence of cases, the treatment and recommen- omy had to be performed during hospitalization dations expressed here are based on the ex- due to hemodynamic deterioration and wors- perience obtained from case reports; there are ening of abdominal pain. no guidelines for the diagnosis and treatment of Peritonitis, appendicitis, intestinal perfo- this entity. ration and an incidental Meckel’s diverticulum were found. After surgery, the patient was taken Case report to the intensive care unit, where antibiotic therapy was administered for 14 days and multiple Two-year old male toddler, admitted to the peritoneal lavages were performed; finally, the emergency room with a diagnostic impres- patient was discharged. sion of intestinal obstruction. Surgical histo- Even though stump appendicitis is not a ry included admission to another institution common cause of acute abdomen, it should due to acute abdomen six months before be kept in mind in patients with history of ap- the new admission. As a result, he under- pendectomy accompanied by abdominal pain, went laparotomy, where generalized perito- who attend the emergency service. Delay in nitis caused by perforated appendicitis was diagnosis and treatment is associated with found, as well as intestinal perforation as- higher morbidity rates and an increase in med- sociated with the inflammatory process; in ical costs. consequence, intestinal resection and end- to-end anastomosis were conducted. Due INTRODUCCIÓN to sepsis of abdominal origin, the patient required laparostomy with several subsequent Stump appendicitis is a rare entity, character- peritoneal lavages and hospitalization in the ized by inflammation of the appendicular rem- ICU. The patient was discharged in good nant after an incomplete appendectomy (1, 2); general conditions, and further data on man- it is not usually considered at first (3), which de- agement are unknown. stump appendicitis in a 2 year-old patient

At the moment of the consultation, the moth- Paraclinical tests er reported symptoms of a day of evolution that Test: Results: began with increasingly diffuse abdominal pain, followed by abdominal distention, multiple ep- • Sodium: 140,6 mmol/L • Potassium: 4,1 mmol/L isodes of vomiting of gastric contents, and Electrolytes • Chlorine: 106 mmol/dL febrile peaks quantified in 39°C, in that or- • Calcium: 9,2 mg/dL der. During physical examination, the patient • Blood urea nitrogen (BUN): was found in poor general condition, with grade Renal function 9.8 mg/dL II dehydration, signs of respiratory distress, • Creatinine: 0.17 mg/dL alertness, weight of 9.4 kg and vital signs as Serum glucose 27 mg/dL described in Table 1. The positive findings C-reactive CRP: 48 units were enophthalmos; nose with nelaton cathe- protein ter in permeable right nostril; dry oral mucosa; tachycardia; tachypnea; distended globular Plain abdominal Multiple air-fluid levels with abdomen with abolished intestinal noises and radiography: absence of distal gas (Figure 1) tympanic to percussion; voluntary muscular defense, and pain on palpation. Paraclinical Source: Own elaboration based on the data obtained in the study. tests were requested, yielding the results sum- marized in Table 2.

Table 1. Vital signs on admission to the emergency room.

Vital signs

Blood pressure 105/65mmHg Heart rate 160 beats per minute Respiratory rate 42 breaths per minute Temperature 37°C Oxygen saturation 90% with 21% FiO² Source: Own elaboration based on the data obtained in the study.

Table 2. Reports of paraclinical tests performed.

Paraclinical tests

Test: Results: • Leukocytes 14430/µL • Neutrophils 73,5% • Lymphocytes 19,8% Fig 1. Plain abdominal x-ray (red arrows). Blood count • Monocytes 6,3% Absence of distal gas (blue arrow); air-fluid • Hemoglobin 11,7g/dL • Hematocrit: 34.7%, levels (red levels). Platelets: 654000 Source: Own elaboration based on the data obtained in the study. case reports

The first suspicion was intestinal obstruc- The patient was referred to the ICU for tion, so a non-surgical medical treatment was postoperative care under the diagnosis of ab- initiated. However, the clinical symptoms of the dominal septic shock; piperacillin-tazobactam patient were persistent with clinical signs of was used for treatment. Subsequently, the pa- systemic inflammatory response, and physical tient underwent a new intervention, and two examination showed deterioration of abdominal new abdominal cavity lavages were performed. pain despite initial management; for this rea- A 14-day antibiotic scheme was completed, son, the patient was referred to the pediatric and finally, the patient presented satisfactory surgery service for an emergency exploratory evolution and was discharged. laparotomy due to acute abdomen. Performing an abdominal ultrasound or a tomography of DISCUSSION the abdomen and pelvis was not possible because of the rapid deterioration of the patient. The main postoperative complications asso- The findings during surgery were severe ciated with appendectomy include surgical adhesion syndrome, contained intestinal per- site infection, intra-abdominal abscesses, in- foration of 5 mm in the anti-mesenteric border testinal perforation, bleeding and adhesions; at 1 m from the Treitz angle, acute perforat- nevertheless, the frequency of stump appen- ed stump appendicitis based on generalized dicitis is low, since only one case is report- peritonitis (Figure 2), and unperforated Meck- ed in every 50000 patients (0.002%) with a el’s diverticulum at 50 cm of the ileocecal history of appendectomy (6,8) or even less, valve (Figure 3). Based on these findings, 0.0014% (9). This figure may be higher since laparotomy, appendectomy, generalized peri- there are cases that are not reported (10), tonitis drainage with cavity lavage, adhesion and because only population in general is release, diverticulectomy, enterorrhaphy, and mentioned, without making a clear distinction skin closure were performed. of the pediatric population.

Fig 2. Stump appendicitis, intraoperative findings. The length of the stump, which is greater than 1 cm (blue square), and the cecum (blue arrow) can be seen. Source: Own elaboration based on the data obtained in the study. stump appendicitis in a 2 year-old patient

Fig 3. Meckel’s diverticulum (blue circle). Intraoperative findings. Source: Own elaboration based on the data obtained in the study.

Stump appendicitis is a rare cause of acute surgeon to adequately visualize the base of the abdomen in children; therefore, considering appendix and, therefore, a long stump was left. this condition is not common for emergency There is a discussion on whether the in- physicians while diagnosing a patient with ab- crease in this entity is related to laparoscopic dominal pain (5). The length of the appendic- surgery (6), although there is no proven evi- ular stump (11, 12) is considered as a pre- dence. Some authors argue that the absence disposing factor, when the length is equal to of tactile perception and two-dimensional or greater than 6 mm (6, 13, 14). This pathol- view predispose to a long appendiceal stump, ogy can appear from 4 days (6, 7, 15) to 50 thus causing a new process of appendicitis years after appendectomy, at any age (1). The (10); however, a retrospective study by Liang review by Bing Tang et al., shows that, until et al. showed that 66% of patients presented 2010, there were only 10 cases reported in with a history of open appendectomy (14, 16, the English literature regarding the pediatric 17, 18). The experience at Fundación Hos- population, ranging between ages 8 and 15, pital de la Misericordia, a pediatric referral and with an onset of symptomatology between hospital where 1348 appendectomies were 2 months and 5 years after surgery (13). performed in 2013 and 1100 in 2014, shows Some causes for atypical stump length that only one case was presented in the men- include extensive inflammation, inadequate tioned period. surgical exposure, insufficient surgeon expe- This pathology has a very similar picture rience, or insufficient stump inversion (13). In to that of acute appendicitis, characterized the case presented here, the extensive inflam- by abdominal pain (may be predominant in matory and necrotic process presented during the lower right quadrant), anorexia, vomiting the acute appendicitis made it difficult for the and fever (2, 3, 5, 10, 15). About 70% of case reports

the cases are associated with perforations generate perforation and transitively worsen the generated as complications of the pathol- condition (13). It is important to consider that ogy (16), in contrast to 16 to 30% of the the images are not diagnostic, but they help the perforations caused by acute appendicitis surgeon in decision-making and should always (19). Furthermore, the formation of an infect- be accompanied by clinical suspicion. ed fistula, inflammatory masses in the lower Management in all case reports is always right quadrant, and presence of signs of peri- surgical and may be open or laparoscopic de- toneal irritation (13) can be related as well. pending on the surgeon’s decision and the ex- In some cases, the condition may present tent of the condition (13). Since this diagnosis subacute abdominal pain; Roberts et al. con- is associated with a high rate of complications, cluded, after reviewing different case reports, it is best to prevent by leaving a stump smaller that abdominal pain is the main symptom and than 5 mm, since a greater length may cause that it occurs in up to 77% of cases (15). Diag- a fecolith (15, 18). nosis is based on clinical suspicion, and the use Subramanian et al. propose some recom- of diagnostic imaging may help increase cer- mendations to obtain a “critical view” of the tainty (17). Diagnostic aids include ultrasound, anatomical structures during laparoscopic tomography, and barium enemas (7, 13). cholecystectomy, for example, thus reducing While performing ultrasounds, the same cri- to the maximum the chances of a long stump. teria for acute appendicitis can be used to diag- First, they recommend to clearly locate the nose stump appendicitis: diameter greater than union of the cecum with the appendix and tran- 6 mm in a transverse section of the appendix, sitively the base, for which the teniae coli must edema of the mucosa or presence of a fecolith be followed to the base, and then, to establish in the right iliac fossa (2, 13, 20). Meanwhile, the union of three virtual axes corresponding during abdominal-pelvic axial tomography, the to the terminal ileum, cecal appendix and teni- findings may be non-specific because of ap- ae coli to obtain the “critical view” of the base; pendectomy or abscess, thickening with in- the appendix must be located at 10 o’clock, flammatory changes at the base of the cecum, the teniae coli at 3 o’clock and the terminal ile- inflammatory mass, increased edema in pe- um at 6 o’clock. Finally, the mesoappendix can ripheral adipose tissue and tubular thickening, be dissected and the appendicular base can among others. Tomography is recommended be located more easily (18, 22). as the initial choice because of the speed with The use of antibiotics and the correction of which it can be performed and because it is not other disorders is at the discretion of the at- a dependent operator (5, 7, 11, 13, 14, 21). tending physician, who must make a decision Barium enema may be useful when abdom- according to intraoperative findings and pa- inal-pelvic tomography is not conclusive, and tient evolution. However, post-surgical man- especially when the surgical incision has had agement and complications are very similar to a torpid evolution; with this imaging modality, a those of an appendectomy, so it all depends pathognomonic sign of “bird-beak” can be on the surgeon’s criteria. observed as an evidence of appendicular re- It should be noted that, due to the low inci- tention, although it actually demonstrates the dence of cases, there are no guidelines for the presence of a long stump and not of inflam- diagnosis and treatment of this entity; therefore, mation. Barium enema is not recommended the therapeutic management performed and in the acute phase of the pathology since it can the recommendations formulated are based stump appendicitis in a 2 year-old patient

on the experience described in the published 2. Martínez-Chamorro E, Merina-Castilla A, case reports. The increase in costs is related Muñoz-Fraile B, Koren-Fernández L, Bo- to the increase in hospitalization days, the need rruel-Nacenta S. Stump appendicitis: preopera- for hospitalization in the ICU in some cases, as tive imaging findings in four cases. Abdom Ima- well as to surgical reinterventions, and a great- ging. 2013;38(6):1214-19. http://doi.org/bx97. er use of medications, among others. 3. Geraci G, Di Carlo G, Cudia B, Modica G. Stump appendicitis. A case report. Int J Surg CONCLUSIONS Case Rep. 2016;20:21-3. http://doi.org/bx98. 4. Walsh DC, Roediger WE. Stump appendicitis-a Stump appendicitis is a rare condition, although potential problem after laparoscopic appendicec- it should be considered in patients with abdom- tomy. Surg Laparosc Endosc. 1997;7(4):357-8. inal pain and a history of appendectomy, due to 5. Waseem M, Devas G. A child with appendicitis af- the high risk of morbid complications and the ter appendectomy. The Journal of Emergency Me- possible sequelae, along with increased atten- dicine. 2008;34(1): 59-61. http://doi.org/dfd6qp. tion costs. A length greater than 5 mm in the 6. García-Baglietto A, Barceló-Cañellas C, stump has been identified as a risk factor, and Marhuenda-Irastorza C. ¿Existe la apendici- some authors associate it with laparoscopic tis del muñón apendicular? Cir Pediatr. 2015 surgery, although there is no evidence to sup- [cited 2017 Feb 5];28(4):208-10. Available port this assertion. from: https://goo.gl/rd7hRu. The clinical picture is similar to classical 7. Ríos RE, Villanueva KM, Stirparo JJ, Kane appendicitis, and some diagnostic images KE. Recurrent (stump) appendicitis: a case se- help to reinforce the diagnostic suspicion; ries. Am J Emerg Med. 2015;33(3):480.e1-2. tomography is considered the initial exam- http://doi.org/bx99. ination of choice due to its ease and speed. 8. Mangi AA, Berger DL. Stump appendicitis. Management is always surgical and postop- Am Surg. 2000;66(8):739-41. erative treatment depends on the surgeon’s 9. Andrade Martínez-Garza P, Robles-Lan- judgment and surgical findings. As a pre- da LP, Reyes-Espejel LG, Visag-Castillo ventive measure, therefore, leaving a stump VJ, Olvera-Guarneros NT. Apendicitis del equal to or less than 5mm during surgery is muñón apendicular. Reporte de caso y revi- advisable, as well as obtaining a critical view sión de literatura. Cirujano general. 2011 [ci- of the anatomical structures in order to prop- ted 2017 Feb 5];33(1):58-62. Available from: erly locate the base of the cecum appendix. https://goo.gl/8NxZtW. 10. Constantin V, Popa F, Carâp A, Socea B. CONFLICTS OF INTEREST: Stump appendicitis - an overlooked clinical entity. Chirurgia (Bucur). 2014;109(1):128-131. None stated by the authors. 11. Gupta R, Gernshiemer J, Golden J, Narra N, Haydock T. Abdominal pain secondary to REFERENCES stump appendicitis in a child. J Emerg Med. 2000;18(4):431-3. http://doi.org/db7zs3. 1. Shin LK, Halpern D, Weston SR, Meiner EM, 12. Nahon P, Nahon S, Hoang JM, Traissac L, De- Katz DS. Prospective CT diagnosis of stump las N. Stump appendicitis diagnosed by colonos- appendicitis. AJR Am J Roentgenol. 2005; 184(3 copy. Am J Gastroenterol. 2002;97(6):1564 -5. Suppl):S62-4. http://doi.org/bx96. http://doi.org/dmwwdb. case reports

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https://revistas.unal.edu.co/index.php/care/article/view/59982

REYNOLDS SYNDROME: A RARE RHEUMATOLOGIC DISEASE THAT INTERNISTS SHOULD HAVE IN MIND. CASE REPORT

Palabras clave: Síndrome de Reynolds; Esclerodermia Limitada; Cirrosis Biliar; Fenómeno de Reyunad; Hipertensión Pulmonar (DeCS). Keywords: Reynolds Syndrome; Scleroderma, Limited; Liver Cirrhosis, Biliary; Raynaud phenomenon; Hypertension; Pulmonary (MeSH).

Jairo Morantes – Caballero, MD Nairo Cano-Arenas, MD Juan Rodríguez de Narváez Department of Internal Medicine Faculty of Medicine – Universidad Nacional de Colombia -– Bogotá D.C. - Colombia

Corresponding author Jairo Morantes – Caballero. Departamento de Medicina Interna, Facultad de Medicina, Universidad Nacional Colombia. Carrera 30 No. 45-03, edificio 471, oficina 510. Phone number: +57 1 3165000 Ext: 15011. Bogotá D.C, Colombia. Email: [email protected] case reports

ABSTRACT INTRODUCTION

Introduction: Reynolds syndrome (RS) is an Reynolds syndrome (RS) is an autoimmune autoimmune disorder characterized by over- disease characterized by overlapping primary lapping primary biliary cirrhosis (PBC) and biliary cirrhosis (PBC) and limited cutaneous limited cutaneous systemic sclerosis (lcSSc). systemic sclerosis (lcSSc); it affects wom- Some published cases do not report pulmo- en mainly, and shows an incomplete form of nary arterial hypertension (PAH), and diagno- scleroderma. Usually, PBC, in the context of ses are usually based on clinical, immunolog- RS, is associated with symptoms that evolve ical and histological findings, mainly focused slowly and that are tolerated by patients; it also on dermatologic features, on those associated implies a good prognosis if compared with with Sjögren’s syndrome, or on an interesting scleroderma or PBC alone, although diagnosis presentation of malignant thymoma; only one may be delayed. case of reported PAH was found, but it was While the prevalence of pulmonary arterial an image report. hypertension (PAH) in systemic sclerosis patients is about 12% —with a significant relat- Case Presentation: This paper reports the ed mortality rate at 3 years after the diagnosis case of a 75-year-old woman who presented of PAH (1)— the prevalence in some studies with some of the features mentioned above, increases to 26% in RS, negatively affecting severe PAH, dyspnea for one month and two prognosis (2). Some published cases do not weeks of purulent expectoration, as well as report PAH, and diagnosis is based on clin- generalized pruritus, nasal telangiectasias, Ray- ical, immunological and histological findings, naud phenomenon, sclerodactyly, and high lev- focusing mainly on dermatologic features (3- els of alkaline phosphatase and transaminases. 9), associated Sjögren’s syndrome (10) or Pulmonary arterial hypertension was doc- as an uncommon presentation of a malignant umented through a transthoracic echocar- thymoma (11). diogram, and inmunoflorecence reported Only one case of reported PAH was found, mitochondrial and centromere patterns of an- but it was an image report (12). The case tinuclear-antibodies. Consequently, RS was di- presented here not only some of the features agnosed and phosphodiesterase type-5 inhibi- mentioned above, but also severe PAH as part tors were started for PAH treatment resulting in of a study on dyspnea in a woman with both the improvement of dyspnea. lcSsc and PBC, who was frequently misdi- agnosed with an exacerbation of chronic ob- Conclusion: Dyspnea could be caused by structive pulmonary disease. many conditions, but in the presence of clinical and physical findings, it suggests an au- CASE PRESENTATION toimmune disorder. Scleroderma should be considered and, additionally, PAH should be in- 75-year-old woman from Bogotá (Colombia), vestigated since it is present in up to 10% of pa- hospitalized in 2014 due to a history of one tients, conferring a worse prognosis. Internists month of dyspnea, aggravated by 2 weeks should keep in mind that these disorders may of orthopnea, and purulent expectoration. be associated with other autoimmune diseases. Further research found that the patient pre- reynolds syndrome: a rare rheumatologic disease that internists should have in mind

sented with generalized pruritus, erythema, experienced productive cough with purulent non-foveal edema in lower limbs and pyrosis expectoration for 2 weeks before consultation. the year before. The patient’s history showed Further investigation revealed that the pa- exposure to tobacco smoke (12.5 pack-year) tient had a previous history of Raynaud’s phe- and alcohol intake once a week since her nomenon and pyrosis. Initial cardiorespiratory twenties, as well as chronic bronchitis man- examination showed a heart rate of 66 beats aged with oxygen (the patient stopped using per minute, arterial pressure of 108/58 mmHg the oxygen and did not have a prior spiro- (systolic/diastolic pressure), respiratory rate metric test) that required hospitalization with of 19 breaths per minute, perioral cyanosis, adequate recovery. The patient did not have third degree jugular venous distention, loud a diagnosis of diabetes mellitus, systemic ar- tricuspid S2 sound, respiratory distress that terial hypertension, nephropathy or hepatop- required using accessory muscles, coarse athy. No family history was disclosed. crackles in both lungs, hepatomegaly and non-foveal edema in the lower limbs painful Clinical findings on palpation. Physical examination confirmed second- Since 2009, the patient had persistent cough ary Raynaud phenomenon, and generalized without expectoration for more than three pruritus, which was her main symptom, af- months, and dyspnea class III according to the fecting the thorax, abdomen, back and legs. functional classification by the New York Heart Skin inspection showed nasal telangiecta- Association (NYHA), which eventually pro- sias, pruritic erythema in abdomen, back and gressed to NYHA IV, with orthopnea and par- limbs with signs of scratching, red hands, and oxysmal nocturnal dyspnea; additionally, she sclerodactyly (Figure 1).

Fig 1. Raynaud’s phenomenon. Source: Own elaboration based on the data obtained in the study. case reports

Initial studies included total blood count 38.9mmHg; bicarbonate (HCO3): 23.6 mE- (normal), electrolytes (sodium:137 mEq/Lt, q/L; base excess: -1.7; oxygen partial pressu- potassium: 3.82 mEq/Lt, chlorine:103 mEq/ re (pO2): 95.1mmHg; ratio PaO2/FiO2: 297, Lt), urine test (normal), arterial blood gases in- lactate 0.8 mmol/L), creatinine and blood ureic terpreted at 560mmHg atmospheric pressure, nitrogen (1.1 mg/dl and 29.25 mg/dl, respecti- which showed a chronic compensated respira- vely). Chest radiography showed an increased tory acidosis without oxygenation disorder (pH cardiothoracic index and signs of pre-capillary 7.38; partial pressure of carbon dioxide (pCO2): pulmonary hypertension (Figure 2a and 2b).

Fig 2A. RChest radiograph. Posteroanterior view. Source: Own elaboration based on the data obtained in the study.

Fig 2B. Left lateral view of chest radiograph. Both projections show pneumonia in the anterobasal segment of the left lower lobe and inferior lingular segment, right middle lobe atelectasis, enlarged cardiac size with pleural effusion and pericardial effusion. Additionally, signs of precapillary pulmonary hypertension can be observed. Source: Own elaboration based on the data obtained in the study. reynolds syndrome: a rare rheumatologic disease that internists should have in mind

Liver profile studies were conducted (Table high levels of alkaline phosphatase (357 IU/L, 1) showing slightly high bilirubin (conjugated: reference value: < 250 IU/L); partial thrombo- 0.38 mg/dL (47%); unconjugated bilirubin: plastin time: 34.5 sec (control 32.6), prothrom- 0.42 (53%) mg/dL; total: 0.8 mg/dl) and tran- bin time: 16.7sec (control 12.9), and serum saminases (ALT 80.5 U/L, AST 82.6 U/L) with albumin test: 3.21 gr/dL.

Table 1. Hepatic and immunological tests. Test Value in patient Total: 0.8 mg/dl Bilirubin Conjugated: 0.38 mg/dL (47% of total) Unconjugated: 0.42 mg/dL (53% of total) Alanine transaminase: 80.5 U/L Transaminases Aspartate transaminase: 82.6 U/L 201 UI/ml Gamma-Glutamyl transferase (Reference value: women 6-42 UI/ml) 357 IU/L Alkaline phosphatase (Reference value: < 250 IU/L) Partial thromboplastin time: 34.5 sec (control 32.6) Coagulation test Prothrombin time: 16.7 sec (control 12.9). Serum Albumin Test 3.21 gr/dL C3: 118.9 mg/dl reference value 90-180 mg/dl Complement C4: 25.1 mg/dl reference value 10-40 mg/dl). Antinuclear antibodies: 1:2560 dils. Antibodies by indirect immunofluorescence ACAs: 1:2560 dils. AMAs: 1:2560 dils. HBSAg: Negative. Anti-HBs IgG and M: Not reactive. Hepatitis virus serologic tests Anti HBc: Negative. AntiHC: Negative.

ACAs: anti-centromere antibodies; AMAs: antimitochondrial antibodies; HBSAg: hepatitis B surface antigen; Anti-HBs: hepatitis B surface antibody; Anti HBc: total hepatitis B core antibody; Anti HC: hepatitis C antibody. Source: Own elaboration based on the data obtained in the study.

An incomplete cholestasis was suspected, Initially, decompensated heart failure by an and a complete ultrasound of the abdomen infectious pulmonary process was considered was requested, revealing congestive hepato- due to the symptoms and the findings obtained megaly, free fluid in the peritoneal cavity, and during physical examination, which were asso- thickening of the gallbladder wall. Measuring ciated with a chronic pulmonary pathology. The GGT levels in blood was determined to con- acute infection was treated with antibiotic the- firm intrahepatic cholestatic injury, obtaining rapy (piperacillin-tazobactam for seven days) a high result (201 UI/ml; reference value: wo- and low-flow oxygen therapy, obtaining some men 6-42 UI/ml). improvement of dyspnea, purulent expectora- case reports

tion cough and absence of crackles on pulmo- was compatible with pneumonia in the antero- nary auscultation. basal segment of the lower left lobe, with pleu- A chronic pulmonary pathology was con- ral and pericardial effusion. A sputum smear sidered as a probably diffuse interstitial pro- was performed searching for M. tuberculosis, cess —based on the findings related to nasal but it yielded negative results. telangiectasias, sclerodactyly, Raynaud phe- Cardiovascular studies included an elec- nomenon and on the radiographic evidence trocardiogram (Figure 3) with a first-degree of pulmonary hypertension (classified as type atrioventricular block and right bundle branch I)— due to limited systemic scleroderma (or block without signs of hypertrophy, ische- CREST syndrome), which along with incom- mia or infarction. Transthoracic echocardio- plete cholestasis, elevated transaminases graphy revealed a depressed left ventricular and pruritus, increases the possibility of an systolic function (ejection fraction of 45%) overlapping primary cirrhosis. and relaxation disorder, also confirming cor A chest radiograph showed increased car- pulmonale with severe pulmonary hyperten- diothoracic index, sign of pre-capillary pulmo- sion (sPAP=73 mmHg) and tricuspid regur- nary hypertension, which was confirmed by hi- gitation grade IV/IV. By epidemiological ne- gh-resolution computed tomography (HRCT); xus with Chagas disease, a Chaga test was no pulmonary fibrosis was found. Also, HRTC requested, but it reported a negative result.

Fig 3. 12-lead electrocardiogram. Findings include first-degree AV block and right bundle branch block. Source: Own elaboration based on the data obtained in the study. reynolds syndrome: a rare rheumatologic disease that internists should have in mind

In addition, an upper gastrointestinal en- sion, with scleroderma associated to primary doscopy test was performed, reporting erythe- biliary cirrhosis or Reynolds syndrome. System- matous mucosa in the esophagus and antral ic sclerosis is a heterogeneous systemic con- gastritis. nective tissue disease characterized by vascular The diagnosis considered limited systemic endothelial damage in small vessels, autoim- scleroderma, with the possibility of primary mune response associated with specific auto- biliary cirrhosis overlap as the cause of intra- antibodies, and progressive fibroblast dysfunc- hepatic cholestasis; immunological tests were tion leading to an increased deposition of the performed to confirm a common autoimmune extracellular matrix. The main clinical manifes- disorder. Also, serum complement levels were tations include skin thickening and involvement measured, showing normal values, which hel- of internal organs (e.g., gastrointestinal tract, ped ruling out other conditions characterized lungs, heart, kidney, central nervous system). by complement consumption (C3: 118.9 mg/ According to the ACR-EULAR criteria for dl. Reference value: 90-180 mg/dl; C4: 25.1 the classification of systemic sclerosis, patients mg/dl. Reference value 10-40 mg/dl). with a total score of nine or more are classified Antinuclear antibodies by indirect immu- as definite systemic sclerosis; skin thickening in nofluorescence showed positive results [antinu- the fingers of both hands with extension to the clear antibodies: positive with anti-centromere proximal metacarpophalangeal joints comple- antibodies (ACAs) = 1:2560 dilutions. Anti-mi- tes the criteria for diagnosis (13). tochondrial antibodies (AMAs) = 1:2560 dilu- Moreover, the liver is a lymphoid organ in- tions)], confirming the presence of two specific volved in the immune response and in the patterns of antinuclear antibodies (ANA) for lo- maintenance of tolerance to self-molecules, calized scleroderma and primary biliary cirrho- but it is also a target for autoimmune reactions, sis; viral hepatitis serologic tests were negative. as observed in primary biliary cirrhosis (PBC) Based on these findings, the patient was (14). PBC is a chronic cholestatic disease, of successfully treated with an angiotensin recep- unknown cause, which shows a slow and pro- tor blocker (Losartan), proton pump inhibitors gressive destruction of small intrahepatic bile (meprazole) and antihistamines (Loratadine) to ducts, impaired biliary secretion and stasis of minimize the effects of the pathology; also, Sil- bile acids within the liver that can produce liver denafil —a selective phosphodiesterase-5 inhi- fibrosis and cirrhosis (15). This disease causes bitor— was administered at 50 mg twice a day the increase of serum alkaline phosphatase — for 4 weeks to treat type I PAH, which improved more than 1.5 times above the normal limit— respiratory symptoms. After being discharged, and is characterized by the presence of anti-mi- the patient was referred for outpatient moni- tochondrial antibodies (AMAs), liver histology toring by internal medicine and rheumatology, with non-suppurative destructive cholangitis, preserving the treatment and, subsequently, and destruction of interlobular bile ducts. A pa- achieving the improvement of symptoms. tient who meets two of these three criteria is diagnosed with PBC (16). DISCUSSION Mid and late 50s is the average age of onset in various studies, and women are affected This patient presented with cor pulmonale sec- by this condition more frequently (17). Fur- ondary to a type 1 pulmonary arterial hyperten- thermore, PBC can be associated with many case reports

immunological disorders like systemic lupus PAH is another aspect included in the erythematosus (2.7–15%), Sjögren syndrome ACR-EULAR criteria for the classification of (35–57%), serum anti-phospholipid antibodies systemic sclerosis. It is defined as an eleva- (75%) and systemic sclerosis (the prevalen- ted mean pulmonary artery pressure (mPAP) ce of systemic sclerosis among patients with —25 mmHg— with a pulmonary capillary wed- PBC is 7–12%, while PBC has been reported ge pressure of 15 mm/Hg. The prevalence of in 2.5% of SSc cases (14)). In the case pre- PAH among patients with SSc varies among sented in this paper, the patient had previously different studies but rounds 10% (27). In a me- shown dermatologic and respiratory symptoms ta-analysis including twelve studies, the pooled related to scleroderma, and laboratory findings prevalence estimate of PAH in patients with were associated with the mitochondrial pattern systemic sclerosis was 13 % (95% CI, 8.96% of antinuclear antibodies (18); increased phos- to 17.87%) with an I2 figure of 95.5 % (95% phatase alkaline without a high level of bilirubin CI, 94.1% to 96.4%), using a random-effects suggests an asymptomatic or an early stage of model for estimation. autoimmune liver pathology (19-21), therefore, The estimated prevalence of PAH repor- PBC was overlapping SSc. ted in patients with connective tissue disea- Reynolds syndrome is a rare autoimmune ses was of 13 % (95% CI, 9.18% to 18.16%) disease with a possible laminopathy genetic ranging between 2.8 % and 32 % (28). In this substrate (22), and consists in the simultaneous case, respiratory symptoms were the main presence of progressive systemic sclerosis complaint of the patient, and pulmonary hyper- and primary biliary cirrhosis. It was first des- tension was documented in the study becau- cribed by Dr. Reynolds in 1970, who reported se the patient did not tolerate withdrawal of six female patients with pruritus, jaundice and oxygen (since she had clinical signs of pulmo- hepatomegaly with marked elevation of serum nary hypertension, echocardiography was re- alkaline phosphatase activity, and a positive test quested evidencing hypertension). Moreover, for serum mitochondrial antibody (23). Lamins tomography did not show interstitial lung di- are ubiquitous proteins that polymerize to form sease as a cause of PAH. nuclear lamina, a meshwork of intermediate fila- In consequence, looking for type 1 PAH in a ments located under the inner nuclear membra- patient with RS is important because this asso- ne; they are involved in laminopathies, a hetero- ciation is related to poor outcomes. Observa- geneous group of diseases that share clinical tional studies have demonstrated that mortality similarities with SSc. A single heterozygous remains high in SSc patients with PAH; more missense mutation in the Lamin B receptor, specifically, the three-year survival rate for SSc LBR exon 9 (c.1114C/T; p.R372C), leads to a patients with PAH has been estimated in 56%, change from a hydrophilic amino acid (argini- compared with 94% in those without PAH, ne) to a hydrophobic amino acid (cysteine) (24). therefore, constituting itself as a leading cause According to Stadie (25), the coincidence of of morbidity and mortality (1) (26, 29, 30). progressive systemic sclerosis and primary bi- A systematic review suggests that using liary cirrhosis seems to be a favorable associa- transthoracic echocardiogram (TTE), pulmo- tion for the progression of primary biliary cirrho- nary function tests, and NT-ProBNP for scree- sis; in this case, the good prognosis of RS could ning and diagnosis of SSc-PAH (31), in the be affected by a pulmonary complication (26). presence of a low lung diffusing capacity for reynolds syndrome: a rare rheumatologic disease that internists should have in mind

carbon monoxide (DLCO) (45-70%), is asso- senger of the nitric oxide pathway (33-35); it ciated with a 5.6-7.4% of PAH development; is expressed in lung tissue, and may be upre- on the other hand, a decline in DLCO is as- gulated in PAH. sociated with an increase in the specificity for Sildenafil citrate is a selective PDE-5 inhibi- PAH (DLCO ≤ 50%, specificity = 90%). tor, which is orally active and potent according In the DETECT study (29), where a popu- to a clinical trial (SUPER-1) (36) and its ex- lation with SSc was studied, nomograms for tended study (SUPER-2) (37). PAH patients practical application of the algorithm were pro- treated with Sildenafil 20, 40, or 80 mg t.i.d. posed to determine the likelihood of pulmo- have reported good results on 6-min walk dis- nary arterial hypertension and to decide whe- tance, improving and maintaining functional ther to take a TTE, and the subsequent right class (38), haemodynamics parameters (37), heart catheterization, with a sensitivity of 97%. and renal function (increased glomerular fil- This study included seven non-echocardio- tration rate, decreased serum creatinine) (38). graphic variables (predicted FVC%, predicted Finally, this study reports the following limi- DLCO%, current/past telangiectasias, serum tations: 1) the right heart catheterization (RHC) anticentromere antibody, serum N-terminal was not performed despite the high level of pro-brain natriuretic peptide (NTproBNP), sPAP in the patient, considering that the error serum urate, and right axis deviation on ECG) estimation of the right echocardiography is with a prediction model for PAH of 84% [area ±20mmhg (39); 2) nailfold capillaroscopy was under the receiver operating characteristic not available in the institution but the ‘SSc pa- curve (ROC AUC) 95% CI: 79.5 to 89.8] (29). ttern’ was documented, including architectural In this case, only predicted FVC%, predicted disorganization, giant capillaries, haemorrha- DLCO%, and NTproBNP were not included. ges, loss of capillaries, angiogenesis and avas- According to ESC/ERS guidelines for pul- cular areas, which characterize >95% of pa- monary hypertension (30) “the therapy of PAH tients with overt scleroderma (40); 3) magnetic patients cannot be considered as a mere pres- resonance cholangiography of the liver and he- cription of drugs; it is characterized by an in- patic biopsy were not performed because they terdisciplinary strategy and the combination of were not available in our second level medical different drugs plus interventions” (31); thus, center. In spite of these limitations, this case physical activity, nutritional and vaccination re- significantly contributes to knowledge on SR commendations, along with the referral to a with some unusual clinical features. rheumatologist and pneumologist, were given In conclusion, dyspnea could be caused by to the patient. In addition, a pharmacologic the- many conditions, but in the presence of clinical rapy was initiated. and physical findings that suggest an autoim- The treatment of PAH begins with the treat- mune disorder, scleroderma should be consi- ment of the underlying cause when possible, dered, and PAH should also be investigated but in type 1 PAH, options include endothelin since it is present in up to 10% of patients, receptor antagonists (Bosetan or Ambrisetan) conferring a worse prognosis if confirmed. Ad- or phosphodiesterase type-5 (PDE-5) inhi- ditionally, an internist should keep in mind that, bitors (32). PDE-5 inhibitors are involved in after appropriate clinical review and physical this process through the inactivation of cyclic examination, not only the most frequent diag- guanosine monophosphate, the second mes- noses should be considered but also differen- case reports

tial diagnoses bearing in mind autoimmune sis and systemic scleroderma (Reynolds syndro- diseases, especially when there are various me): apropos of 8 new cases. The contribution of organs affected. “Low prevalence” diseases accessory salivary gland biopsy. Rev. Med. Inter- can be overlooked. ne. 1998;19(6):393-8. 9. Brzezińska-Kolarz B, Undas A, Dyczek A, REFERENCES Musiał J. Reynolds syndrome: the combination of scleroderma and primary biliary cirrhosis. Case 1. Chaisson NF, Hassoun PM. Systemic sclero- report. Pol Arch Med Wewn. 2001;105(3):231-4. sis-associated pulmonary arterial hypertension. 10. Trotta F, Potena A, Bertelli R, La Corte R, Chest. 2013;144(4):1346-56. http://doi.org/bzcs. Stabellini G, Negri A. Reynolds syndrome as- 2. Koenig M, Joyal F, Vincent V, Fritzler MJ, Po- sociated with Sjogren’s syndrome. Minerva Med. liquin M, Dominguez M, et al. Cirrhose biliai- 1980;71(19):1385-92. re primitive et sclérodermie systémique : aspects 11. Michaud M, Gaudin C, Brechemier D, Mou- cliniques, biologiques et pronostiques. Rev. Med. lis G, Astudillo L, Lavialle-Guillotreau V, et Interne. 2008;29:S368. http://doi.org/d8bk75. al. Reynolds syndrome revealing a malignant 3. Mahrle G, Müller F, Groth W. Multiples Autoim- thymoma. Rev. Med. Interne. 2013;34(3):171-3. munsyndrom: Assoziation eines Reynolds-Sy- http://doi.org/bzct. ndroms (akrale Sklerodermie, primär biliäre 12. Fukuda Y, Miura S, Saku K. CREST syndro- Zirrhose, Sjögren-Syndrom) mit einem Lupus, me with pulmonary arterial hypertension. Intern erythematodes/Lichen-ruber-planus-Overlap-Sy- Med. 2012;51(4):441-2. ndrom. Der Hautarzt. 2004;55(5):465–70. http:// 13. van den Hoogen F, Khanna D, Fransen doi.org/bh94q7. J, Johnson SR, Baron M, Tyndall A, et al. 4. Riarte MC, Giovanna PD, Pelli MJ, García 2013 classification criteria for systemic sclero- S, Cabrera HN. Cirrosis biliar primaria asocia- sis: an American college of rheumatology/Eu- da a colagenopatías. Piel. 2014 [cited 2017 Feb ropean league against rheumatism collaborative 6];29(1):12-5. Available from: goo.gl/kaC6o7. initiative. Ann Rheum Dis. 2013; 72(11):1747- 5. Bellelli A, Tumiati B, Rossi F, Salvarani C, Por- 55. http://doi.org/bzcv. tioli I. The Reynolds syndrome. Clinical case and 14. De Santis M, Crotti C, Selmi C. Liver abnor- review of the literature. Analogy with graft-versus- malities in connective tissue diseases. Best Pract host disease. G Clin Med. 1981;62(9):656-64. Res Clin Gastroenterol. 2013;27(4):543-51. 6. Tal-Benzecry S, Armero F, Scasso MS, http://doi.org/f2fktg. Machaín M. Síndrome de Reynolds: Descrip- 15. Momah N, Lindor KD. Primary biliary cirrho- ción de un Caso. Hospital Privado de Comu- sis in adults. Expert Rev Gastroenterol Hepatol. nidad. [Cited 2016 March 16]. Available from: 2014;8(4):427-33. http://doi.org/bzcw. goo.gl/hbw6Qc. 16. Bowlus CL, Gershwin ME. The diagnosis 7. Herruzo-Solís JA, Gabriel-Marín JC. Cirrosis of primary biliary cirrhosis. Autoimmun Rev. biliar primaria y síndrome CREST. Rev. esp. en- 2014;13(0):441-4. http://doi.org/bzcx. ferm. dig. 2004 [cited 2017 Feb 6];96(3):219- 17. Ohira H, Watanabe H. Pathophysiology and 20.Available from goo.gl/Qb0z6N. recent findings of primary biliary cirrhosis com- 8. Launay D, Hebbar M, Janin A, Hachulla E, plicated by systemic sclerosis. Hepatol Res. Hatron PY, Devulder B. Primary biliary cirrho- 2014;44(4): 377–83. http://doi.org/bzfw. reynolds syndrome: a rare rheumatologic disease that internists should have in mind

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36. Galiè N, Ghofrani HA, Torbicki A, Barst RJ, Ru- 39. D’Alto M, Romeo E, Argiento P, D’Andrea A, bin LJ, Badesch D, et al. Sildenafil citrate therapy Vanderpool R, Correra A, et al. Accuracy and for pulmonary arterial hypertension. N. Engl. J. Med. precision of echocardiography versus right heart 2005;353(20):2148-57. http://doi.org/fgjrvh. catheterization for the assessment of pulmonary 37. Rubin LJ, Badesch DB, Fleming TR, Galiè hypertension. Int J Cardiol. 2013;168(4):4058- N, , Simonneau G, Ghofrani HA, et al. Long- 62. http://doi.org/bzf7. term treatment with sildenafil citrate in pulmonary 40. Cutolo M, Sulli A, Secchi ME, Paolino S, arterial hypertension: the SUPER-2 study. Chest. Pizzorni C. Nailfold capillaroscopy is useful 2011;140(5):1274-83. http://doi.org/c2q66z. for the diagnosis and follow-up of autoimmune 38. Webb DJ, Vachiery JL, Hwang LJ, Maurey JO. rheumatic diseases. A future tool for the analy- Sildenafil improves renal function in patients with sis of microvascular heart involvement?. Rheu- pulmonary arterial hypertension. Br J Clin Phar- matology. 2006;45 Suppl 4:iv43-6. http://doi. macol. 2015; 80(2):235-41. http://doi.org/bzf6. org/b9ccvn. Case Reports 2017; 3(1)

https://revistas.unal.edu.co/index.php/care/article/view/60912 ACCURATE DIAGNOSE AND MANAGEMENT OF ADVANCED NASAL TYPE EXTRANODAL NK/T CELL LYMPHOMA. A CASE REPORT

Palabras clave: Linfoma Extranodal de Células NK-T; Antineoplásicos; Radioterapia; Granuloma Letal de la Línea Media [DeCS]. Keywords: Lymphoma, Extranodal NK-T-Cell; Antineoplastic Protocols; Radiotherapy; Granuloma, Lethal Midline [MeSH).

Luis Felipe Romero Moreno, MD Juan Sebastián Parra–Charris, MD Ricardo Ángel–Obando, MD Department of Otorhinolaryngology – Faculty of Medicine – Universidad Nacional de Colombia Bogotá, Colombia.

Liliana Ramos–Valencia, MD Faculty of Medicine – Universidad de La Sabana – Bogotá - Colombia.

Corresponding author: Luis Felipe Romero Moreno. Email: [email protected]. Universidad Nacional de Colombia. Calle 83 A- N 116 A- 85. Casa 160. case reports

ABSTRACT cosa of the superior airway and middle facial third (1,2). Extranodal natural killer (NK)/T-cell lymphoma, It is a rare disease that accounts for 7-10% nasal type, is a rare entity in otorhinolaryngolo- of non-Hodgkin lymphomas in Asia and Latin gy. Its management requires skilled physicians America (3) and affects mostly adult men aged in order to suspect this disease and making a between 30 to 40 years. Most of the patients proper diagnosis at early stages. This paper affected by this disease present symptoms for reports the case of a 31-year-old male patient, six months prior to the first consultation (2-4), with one month of nasal obstruction, recurrent with 70% to 90% of cases with a recent or la- sinusitis, palatal ulceration and a necrotizing tent infection with Epstein - Barr virus (EBV) (4). lesion. Histopathology reported lymphoid infil- The survival rate ranges between 35% and 85% trate polymorph angiocentric growth pattern depending on the severity of symptoms and the and extensive areas of necrosis. Immunohisto- local extension. Different case series show a chemistry confirmed the phenotype for T/NK high local recurrence rate of 50% (5) and me- cells: positive CD3, BCL2, CD4 and CD56. tastasis in only 13% of patients in skin, lungs IgG for Epstein-Barr virus was also positive. and gastrointestinal tract, which represents the The initial staging was T4, N1, M0, Eastern order of frequency and worst prognosis (6,7). A Cooperative Oncology Group (ECOG) scale correct diagnosis is important to define the type was 1, with intermediate risk, and low Interna- of treatment, which may include surgical proce- tional Prognostic Index (IPI); based on this re- dures, chemotherapy or radiotherapy (8). sults, the patient was referred to oncology to initiate treatment. After a ten-month follow-up, CASE PRESENTATION the patient’s condition improved, with complete remission of nasal and palate injuries; no This case presents a 31-year old mestizo male relapse has occurred to date. patient, born in Fusagasugá, Colombia, with a This case is a clear example of the impor- history of inhaled cocaine and tobacco abuse. tance of early diagnostic through multiple He works as a painter, with constant expo- biopsies in order to establish a specific treat- sure to inhaled chemicals. The month prior to ment to decrease complication rates and im- consultation, he was treated for acute sinus- prove prognosis. itis with amoxicillin for 10 days due to bilateral nasal obstruction and occasional epistaxis. INTRODUCTION Three weeks before consultation, he noted a painful ulcer in the hard palate, although, no Extranodal natural killer/T-cell lymphoma, na- systemic symptoms were reported. On gen- sal type (NKTL), was the term endorsed by eral examination he was cachectic but stable, the Revised European American Lymphoma and presented with hyponasal speech. Rhi- Classification (REAL) in 2008 (1) to refer to noscopy showed a bilateral mass in the nasal what was previously known as malign gran- cavity with septal perforation in Cottle zones uloma or polymorphic malignant reticulosis. 2 – 3. Hard and soft palate showed a necrotic This lymphoma is one of the most lethal mid- lesion with irregular borders, mucosa swelling line granulomas, which are characterized for without active bleeding. He had no palpable the extensive destructive lesions in the mu- adenopathy on head and neck (Figure 1). accurate diagnose and management of advanced nasal type extranodal nk/t cell lymphoma

Figure 1. Ulcerated lesion in hard palate with necrotic borders. Circle: Delimitation of the site of the biopsy. Source: Own elaboration based on the data obtained in the study.

Blood tests were negative for human immu- neous soft tissue density material; left lamina nodeficiency virus (HIV), venereal disease re- papyracea was eroded and the periorbital fat search laboratory (VDRL) and hepatitis B and had inflammatory changes (Figure 2). Lymph C, and C-reactive protein test (CRP) was less nodes of the neck were compromised at zones than 10 mg/L. Computed tomography scan in IIa y IIb. The upper airway was patent. No lesions face and neck showed a mass occupying the were identified in CT scans of thorax and abdo- nasal cavity, extended to the nasopharynx. The men. The patient was hospitalized and multiple paranasal sinuses were occupied by homoge- punch biopsies of the soft palate were taken.

Figure 2. CT scan of nose and paranasal sinuses. Coronal view: complete occupation of left maxillary sinus, frontal and bilateral ethmoidal sinuses. Arrow: Eroded left lamina papyracea. Source: Own elaboration based on the data obtained in the study. case reports

Broad spectrum antibiotic and pain control thology test for the soft palate biopsy reported treatment were administrated, but during the polymorphous lymphoid infiltrate with angiocen- first week of hospitalization the patient present- tric distribution and extensive necrosis (Figure ed left proptosis and gradual loss of vision. He 3). Immunohistochemistry confirmed lymphoid was taken to the operation room for a left lateral phenotype with positive T/NK CD3, CD4, BCL2 canthotomy, but three days later, the patient de- and CD56; lactate dehydrogenase (LDH) veloped irreversible left amaurosis. The histopa- was negative, and IgG for EBV was positive.

Figure 3. Soft palate biopsy. NK/T extranodal nasal type lymphoma. Arrow. Polymorphous lymphoid infiltrate with angiocentric distribution. Source: Own elaboration based on the data obtained in the study.

The final staging was T4, N1, M0, ECOG Table 1. SMILE chemotherapy regimen (8). 1, IPI of low/intermediate-risk in a patient with SMILE Chemotherapy regimen poor health condition. The patient underwent chemotherapy with SMILE protocol (Table Etoposide 100mg/m2 on days 2-4 1). Only 2 courses of SMILE were adminis- Cyclophosphamide 1g/ m2 on days 2-4 tered with adequate tolerance and some side Mesna 900 mg/m2 on days 2-4 effects, which were easily managed, such as Dexamethasone 40 mg/ m2 on day 2-4 queasiness, vomiting, weight loss and alope- Methotrexate 2g/ m2 on day 1 6000 U/m2 on days 8, cia. Figure 4 shows the improvement of the le- Asparginase sion seven months after initiation of treatment; 10,12,14,16,18,20 finally, after ten months of clinical and radiological surveillance, there was a complete re- DISCUSSION mission of the lesions in oral and nasal cavity. In addition, the patient reported improvement Most of the lethal midline granulomas cor- of nasal obstruction and pain in the palate by respond to NK-cell lymphomas, in which an 90%, but left amaurosis was persistent. angiocentric and angiodestructive lymphocytic accurate diagnose and management of advanced nasal type extranodal nk/t cell lymphoma

proliferation occurs along the midline tis- with recurrent bacterial sinusitis (5,6). As the sue with a fast growing rate. Despite being a disease progresses, a unilateral collapse of low-prevalence pathology in our continent, the the nasal cavity and oronasal fistula may ap- NK-cell lymphoma is being more frequently pear due to edema, necrosis and major de- diagnosed and patient’s survival rate has in- struction of the tissue in the facial midline (6). creased. The initial symptoms are non-specific Cutaneous manifestations have the highest and include nasal obstruction and rhinorrhea prevalence among systemic symptoms.

Figure 4. A. Initial lesion in the palate. B. 7 months after SMILE protocol chemotherapy. Source: Own elaboration based on the data obtained in the study.

The most accurate test for diagnosis in or- ulomatosis, other non-Hodgkin’s lymphomas, der to find atypical lymphocytic infiltrates with aggressive NK cell leukemia and malignant ep- angiocentric distribution is biopsy, and immu- ithelial midline tumors is highly important (1,4). nohistochemistry is always positive for tumor- Early diagnosis is of great relevance for al markers CD3, CD4, CD56, CD40, CD40 better prognosis in order to achieve a high- RO. Infection with EBV and high levels of LDH er survival rate. Bad prognosis markers at the can be found and constitute findings of poor time of diagnosis are extensive local invasion, prognosis (8). Medical imaging with comput- lymph nodes compromise, metastases, high ed tomography and magnetic resonance are levels of LDH, history of EVB infection and useful for determining the size of the lesion, the systemic inflammatory response syndrome presence of osteolysis, as well as extension (6). Likewise, classifying the disease based to adjacent structures (8,9). In Latin America, on the TNM system is essential to define the discarding infectious diseases such as fungal treatment and the prognosis (10) (Table 2). infections, tuberculosis or tertiary syphilis, and Numerous scales of functionality for oncolog- granulomatous diseases like Wegener’s gran- ic patients have been described; therefore, case reports

ECOG performance status and NCCN–IPI CONCLUSIONS are recommended since they are the most ef- fective and practical ways to define the stage Emphasizing on the early diagnosis of one of and prognosis of a lymphoma (11,12). the most lethal midline pathologies can improve prognosis and quality of life. Although, Table 2. TNM classification for Extranodal NK/T cell diagnosis is made based on the first biopsy, lymphoma, nasal type, (10). usually, more than two or three biopsies are Stage Features necessary. For advanced stages, only chemotherapy is mandatory in order to reduce mortal- T1 Confined to nasal cavity ity probabilities. Anterior ethmoidal sinus, maxilar sinus, T2 hard palate CONFLICT OF INTEREST Posterior ethmoidal sinus, sphenoid T3 sinus, frontal sinus, oral cavity Alveolar process, infratemporal fossa, None stated by the authors. T4 intracraneal fossa N0-N1 With or without nodular compromise INFORMED CONSENT M0-M1 Local or far metastases All images have been published with the au- The treatment depends on the staging of thorization of the patient. the disease. NKTL staged as low risk, stage I or II, is treated with chemotherapy and radio- FUNDING therapy with a 5 year survival rate of 91%, compared to 54% for only chemotherapy and 76% None stated by the authors. for only radiotherapy (13). Better results have been accomplished with doses higher than 50 REFERENCES Gy (8-15). Advanced stages III or IV, or with NCCN–IPI greater than 4, with or without ex- 1. Miyake MM, Oliveira MV, Miyake MM, tra nasal compromise, show better response to Garcia JO, Granato L. Clinical and otorhino- only chemotherapy. laryngological aspects of extranodal NK/T cell Multiple protocols of chemotherapy are lymphoma, nasal type. Braz J Otorhinolaryngol. described with asparaginase, cyclophos- 2014;80(4):325-9. http://doi.org/f2sv66. phamide, etoposide, among others, which 2. Tababi S, Kharrat S, Sellami M, Mamy J, can be used in advanced stages, but survival Zainine R, Beltaief N, et al. Extranodal NK/T rates have a clear decrease (8-14). Stem cell cell lymphoma, nasal type: Report of 15 cas- transplant in advanced stages and relapses is es. Eur Ann Otorhinolaryngol Head Neck Dis. currently being considered as an alternative 2012;129(3):141-7. http://doi.org/bxxb. therapy with good results for improving quality 3. Mallya V, Singh A, Pahwa M. Lethal mid- of life and higher survival rates (14,15). Mul- line granuloma. Indian Dermatol Online J. tidisciplinary approaches of this disease are 2013;4(1):37-9. http://doi.org/bxxc. fundamental for the treatment of the patients; 4. De la Rosa-Astacio F, Barberá-Durbán R, Va- new studies are required to evaluate possible ca-González M, Cobeta-Marco I. Linfoma T/ alternatives for mid-face reconstruction in pa- NK laringotraqueal: caso clínico. Acta otorrinolar- tients without relapse. ingol Esp. 2011;62(1):71-3. http://doi.org/ctg9hc. accurate diagnose and management of advanced nasal type extranodal nk/t cell lymphoma

5. Tlholoe MM, Kotu M, Khammissa RA, Bida 11. Vidal E, Deán A, Alamillos F, Salas J, López M, Lemmer J, Feller L. Extranodal natural killer/T- R. Lethal medline granuloma in a human inmu- cell lymphoma, nasal type: ‘midline lethal granu- nodeficiency virus-infected patient. Am J Med. loma.’ A case report. Head Face Med. 2013;9:4. 2001;111:244-5. http://doi.org/c38wt7. http://doi.org/bxxd. 12. Li YX1, Wang H, Jin J, Wang WH, Liu QF, 6. Velázquez-Arenas L, Vázquez-Martínez OT, Song YW, et al. Radiotherapy alone with curative Méndez-Olvera N, Barboza-Quintana O, Gó- intent in patients with stage I extranodal nasal-type mez M, Ocampo-Candiani J. Linfoma de célu- NK/T-cell lymphoma. Int J Radiatat Oncol Biol Phys. las T/NK extranodal tipo nasal. Actas Dermosifil- 2012;82(5): 1809–15. http://doi.org/dvd93f. iogr. 2008;99(4):316-7. http://doi.org/c8d5m5. 13. Chan A, Tang T, Ng T, Shih V, Tay K, Tao M, et 7. Zhang Y, Wang T, Liu GL, Li J, Gao SQ, Wan L. al. To SMILE or not: supportive care matters. J Clin Mucormycosis or extranodal natural killer/T cell lym- Oncol. 2012;30(9):1015-6. http://doi.org/bxxm. phoma, similar symptoms but different diagnosis. J 14. Lee J, Au WY, Park MJ, Suzumiya J, Nakamura Mycol Med. 2016;26(3):277-82. http://doi.org/bxxf. S, Kameoka J, et al. Autologous hematopoietic 8. Chaudhary RK, Bhatt VR, Vose JM. Manage- stem cell transplantation in extranodal natural killer/T ment of extranodal natural killer/t-cell lympho- cell lymphoma: a multinational, multicenter, matched ma, nasal type. Clin Lymphoma Myeloma Leuk. controlled study. Biol Blood Marrow Transplant 2015;15(5):245-52. http://doi.org/bxxg. 2008; 14(12):1356-64. http://doi.org/c6q4tz. 9. Li JH, He HH, Cheng Y, He WJ. Primary Thyroid 15. Suzuki R, Kako S, Hyo R, Izutsu K, Ito T, Extranasal NK/T-Cell Lymphoma Associated With Shinagawa K, et al. Comparison of Autol- Good Outcome: A Case Report and Literature ogous and Allogeneic Hematopoietic Stem Review: A Care-Compliant Article. Medicine (Bal- Cell Transplantation for Extranodal NK/T-Cell timore). 2016; 95(20): e3460. http://doi.org/bxxh. Lymphoma, Nasal Type: Analysis of the Japan 10. Hartig G, Montone K, Wasik M, Chalian A, Society for Hematopoietic Cell Transplantation Hayden R. Nasal T- cell lymphoma and lethal mid- (JSHCT) Lymphoma Working Group; Blood. line granuloma syndrome. Otolaryngol Head Neck 2011 [cited 2017 Jan 30];118(21):503. Avail- Surg. 1996;114:653-6. http://doi.org/c9p7fq. able from: https://goo.gl/Dc2i4X. Case Reports 2017; 3(1)

https://revistas.unal.edu.co/index.php/care/article/view/60484

INFECTED PULMONARY INFARCTION CASE REPORT

Palabras clave: Infarto pulmonar; Embolismo pulmonar; Anticoagulación. Keywords: Pulmonary infarction; Pulmonary embolism; Anticoagulation.

Laura Marcela Velásquez Gaviria, MD Cristian Alejandro Castillo Rodriguez Andrés Garcés Arias, MD Luis David Sáenz Pérez Sebastián Felipe Sierra Umaña, MD Laura Salazar Franco Andrés Fernando Rodríguez Gutierrez, MD Sebastian Salinas Mendoza Department of Internal Medicine Medical Program Faculty of Medicine Faculty of Medicine – Universidad Nacional de Colombia -– – Universidad Nacional de Colombia -– Bogotá D.C. - Colombia Bogotá D.C. - Colombia

Diego Fernando López Donato, MD Luisa Fernanda Patiño Unibio, MD Department of Radiology Department of Internal Medicine Faculty of Medicine Faculty of Medicine – Universidad Nacional de Colombia -– – Pontificia Universidad Javeriana -– Bogotá D.C. - Colombia Bogotá D.C. - Colombia

Corresponding author Sebastián Felipe Sierra Umaña. Universidad Nacional de Colombia Facultad de Medicina, Departamento de Medicina Interna – Sede Bogotá – Colombia. Email: [email protected] case reports

ABSTRACT ticoagulant and antimicrobial treatment should be initiated in a timely manner. Introduction: Pulmonary infarction occurs in 29% to 32% of patients with pulmonary INTRODUCTION thromboembolism (PTE). The infection of a pulmonary infarction is a complication in ap- Pulmonary thromboembolism (PTE) is the third proximately 2 to 7% of the cases, which makes leading cause of death related to cardiovas- it a rare entity. cular disease, in which acute right ventricular failure and pulmonary infarction are the main Case Presentation: 49-year-old woman complications (1). Some studies have report- with pleuritic pain in the left hemithorax that ed that pulmonary infarction occurs in 29% to irradiated to the dorsal region, associated with 32% of patients with PTE (1-3). dyspnea and painful edema in the left lower Pulmonary infarction secondary to pul- limb of two days of evolution. Two weeks prior monary embolism is more common in pa- to admission, the patient suffered from a left tients with low cardiopulmonary reserve (4). knee trauma that required surgical interven- A study showed that pulmonary infarctions tion; however, due to unknown reasons, she in patients with PTE occurred in 36% of did not receive antithrombotic prophylaxis. congestive heart failure cases, and in 54% Physical examination showed tachycardia, of patients with hypotension and shock (5). tachypnea and painful edema with erythema Nevertheless, more recent studies have indi- in the left leg. After suspecting a pulmonary cated that young patients with good health thromboembolism, anticoagulation medication status prior to PTE can have a higher inci- was administered and a chest angiotomogra- dence of pulmonary infarction (6,3). In ad- phy was requested to confirm the diagnosis. dition, a high thrombotic burden has been The patient experienced signs of systemic associated with an increased probability inflammatory response, and respiratory deteri- of pulmonary infarction, although this is ob- oration. A control tomography was performed, served in small pulmonary arteries (7). suggesting infected pulmonary infarction. Anti- In general, pulmonary infarction causes biotic treatment was initiated, obtaining pro- pleuritic pain, tachypnea, dyspnoea and, in ex- gressive improvement; the patient was sub- tremely rare cases, coughing with hemoptysis sequently discharged, and continued with (8); therefore, radiological differentiation from anticoagulation medication and follow-up on an other entities such as masses, atelectasis and outpatient basis. pneumonia is difficult. Pulmonary infarction is usually observed in Conclusions: Pulmonary infarction is a fre- subpleural regions and occurs predominantly quent complication in patients with PTE. There- in the lower lobes, especially the right lobe. The fore, infected pulmonary infarction should be most common radiological finding is a triangu- suspected in patients with clinical deteriora- lar consolidation of the pulmonary parenchyma tion and systemic inflammatory response. The (50%), although segments with a ground glass radiological difference between pulmonary in- pattern (35.9%) and Hampton sign (14.5%) farction and pneumonia is not easily identified, can also be observed, which help to differen- thus the diagnostic approach is clinical, and an- tiate it from masses and pneumonia (6,9,10). infected pulmonary infarction

Multiple complications have been associat- gion, associated with sudden dyspnea, edema, ed with pulmonary infarction, including pneu- and warm sensation on the lower left limb; no monia, pneumothorax, bronchopulmonary fistu- fever, coughing or hemoptysis were reported. la, alveolar hemorrhage, cavitations, empyema Two weeks prior to consultation, the patient un- and pulmonary abscess (11). Infection asso- derwent meniscus reconstruction, and anterior ciated with pulmonary infarction is a rare but and posterior cruciate ligament and left knee important complication, as it may result in the chondroplasty secondary to a closed trauma. formation of abscesses and empyemas that No postoperative antithrombotic prophylax- may require surgical drainage. is was performed after the procedure due to The obstruction of a pulmonary vessel sec- unknown reasons. The patient had an import- ondary to a sterile plunger is suggested to ant history of class 1 obesity, with no previous be the cause of blood extravasation into the pathological, toxic or allergic symptoms nor surrounding tissues, of edema in adjacent previous hospitalizations. bronchial walls, and of the increase of endo- Physical examination on admission showed bronchial secretion, which forms a favorable a normal general condition, with blood pres- environment for colonization and bacterial in- sure of 97/63 mmHg, heart rate of 106 bpm, fection by air or blood (12). Bashir & Benson respiratory rate of 20 rpm, oxygen saturation (13), based on a series of postmortem stud- at 96%, oxygen inspired fraction of 0.21, and ies, estimated the incidence of lung infarction axillary temperature of 36.5°C. Her height was infection in 2 to 7% (13). The presence of fe- 160 cm and weight 83 kg, which showed a ver, sweating, tachycardia, purulent sputum, body mass index (BMI) of 32.4 kg/m2. Thorax as well as of deterioration of the general con- auscultation showed P2> A2 without mur- dition and leukocytosis after pulmonary infarc- murs; fine crackles were also identified in the tion, is highly suggestive of infection, which is base of the left lung. Edema in the foot and why the spectrum of etiological agents is con- proximal third of the leg was found in the low- sidered similar to that described in nosocomial er left limb, with local erythema and superficial pneumonia (11). In cases of infected pulmo- pain on palpation. nary infarction, anticoagulant and antibiotic The following tests were performed: blood therapies should be initiated timely and se- count, electrolytes, blood urea nitrogen (BUN) lected according to local resistance patterns, and creatinine, which were within normal lim- associated pathogens, patient characteristics its. On the other hand, the electrocardiogram and clinical context in general (5). showed sinus tachycardia, while the echo- This paper reports a case compatible with cardiogram had a structural and functionally pulmonary thromboembolism complicated by normal heart. Finally, the chest X-ray revealed infected pulmonary infarction. left basal lamellar atelectasis and right atrium growth (Figure 1). CASE PRESENTATION The Wells scale was applied, finding a high probability for pulmonary thromboembolism. 49-year-old female, public accountant, from Anticoagulation was initiated with low molec- Bogotá, Colombia who consulted due to a two- ular weight heparin (enoxaparin) at a dose of day long clinical picture involving pleuritic pain 1 mg/kg every 12 hours, and a computed ax- in the left hemithorax, irradiated to the dorsal re- ial angiography (AngioCAT) of the chest was case reports

performed, confirming the diagnostic suspi- in the trunk of the lower left basal segment cion by reporting pulmonary artery obstruction (Figure 2).

Fig 1. Posteroanterior chest X-ray. Image in left basal band corresponding to atelectasis (arrow). Source: Own elaboration based on the data obtained in the study.

Fig 2. Angiotomography of the chest. Axial plane. Pulmonary embolism, filling defect in the shape of a life preserver sign (arrow). Source: Own elaboration based on the data obtained in the study. infected pulmonary infarction

Surprisingly, after initiating anticoagulation C-reactive protein and a significant increase and other general treatment measures indi- in leukocytes at neutrophils expense. A new cated for pulmonary thromboembolism, and chest tomographic evaluation was performed, about three days after her hospitalization, the in which wedge densities were identified in the patient required increased oxygen flow through middle and lower right lobes and in the lower nasal cannula, her chest pain worsened, and left lobe, as well as an aerial bronchogram of presented with dyspnea, fever, leukocytosis, the right lower lobe and bilateral pleural effu- tachycardia, and tachypnea. Control para- sion (Figure 3 and 4). No blood cultures or clinical exams were requested, revealing high sputum cultures were performed.

Fig 3. Angiotomography of the chest. Coronal plane. Pulmonary embolism, filling defect configuring the railway track sign (arrow), left basal consolidation of the pleural base and air bronchogram corresponding to pulmonary infarction (star). Source: Own elaboration based on the data obtained in the study.

With this in mind, infected pulmonary in- at a dose of 5 mg every 24 hours. After com- farction was diagnosed and broad-spectrum pleting the seventh day of antibiotic treatment antibiotic therapy with piperacillin + tazobac- and with INR (International Normalized Ratio) tam was initiated at a dose of 4.5 g intrave- within the therapeutic range, she was dis- nously every six hours, considering that the charged with anticoagulation prescription infection was nosocomial and that the patient for three months initially, and internal medicine had undergone a recent hospitalization, thus outpatient controls. No adverse reactions to increasing the risk of resistant germs. treatments during hospitalization were ob- The patient improved progressively, and served. Figure 4 shows the timeline of the re- oral anticoagulation with warfarin was initiated ported case case reports

Fig 4. Chest AngioCAT. Broad base consolidation, hilar apex, obtuse borders that coincide with pulmonary infarction (star), pleural effusion (arrow). Source: Own elaboration based on the data obtained in the study.

Anticoagulation treatment Antibiotic treatment

Surgical Trauma in procedure Deep Pulmonary Infected lower vein thrombo- Pulmonary pulmonary without infarction limb antithrombotic thrombosis embolism infarction prophylaxis

Consultation

Week 1 Week 2 Week 3 Week 4 Week 5

Fig 4. Timeline. Source: Own elaboration based on the data obtained in the study.

DISCUSSION nary infarction and infection of the necrotic lung tissue. This case is relevant from several This case shows the clinical evolution of a pa- points of view, since it points the importance tient with PTE, which progressed to pulmo- of thrombus prophylaxis in patients at risk, infected pulmonary infarction

and exposes complications that endanger this entity, in order to improve care and clinical patients’ lives and generate diagnostic, ther- outcomes of patients. apeutic and research challenges. In conclusion, pulmonary infarction is a com- Many risk factors are associated with pul- mon complication of pulmonary thromboembo- monary thromboembolism; in this case, the lism, which can become infected on rare occa- patient presented trauma, surgery, immobility sions. Consequently, a high degree of clinical and obesity (14). The incidence of PTE can suspicion and adequate interpretation of the be reduced by performing thrombus prophy- evolution are necessary to establish the diag- laxis in patients undergoing orthopedic knee nosis and to provide timely management. surgery, particularly in the presence of addi- Patient Perspective: the patient expressed tional risk factors (15). Therefore, prophylaxis gratitude for receiving medical care in an ap- until patients recover mobility is highly rec- propriate and humanized way. ommended (16). Informed consent: the patient consented PTE diagnosis was obtained by following the publication of the information used in this the guidelines for clinical practice (17), that is case report. to say, by classifying the probabilities through Wells scale and confirming the diagnosis with CONFLICT OF INTEREST the test of choice, in this case, chest AngioCAT. On the other hand, the evolution of the pa- None stated by the authors. tient’s clinical picture, besides the development of systemic inflammatory response, elevation of FUNDING acute phase reactants, exacerbation of pleuritic pain and respiratory deterioration, caused the None stated by the authors. suspicion of infected pulmonary infarction (8). This clinical presentation, along with compati- REFERENCES ble diagnostic images, was the basis of the diagnosis. In this case, a significant improvement 1. Kirchner J, Obermann A, Stückradt S, Tüs- was achieved, allowing hospital discharge and haus C, Goltz J, Liermann D, et al. Lung In- a good short- and long-term prognosis. farction Following Pulmonary Embolism: A Com- Nevertheless, it is important to mention that parative Study on Clinical Conditions and CT this report has significant limitations: the lack Findings to Identify Predisposing Factors. Rofo. of microbiological isolates to determine the 2015;;187(6):440-4. http://doi.org/bx9z. etiological agent, the lack of clinical practice 2. Gadkowski LB, Stout JE. Cavitary pulmonary guidelines for the diagnosis and treatment of disease. Clin Microbiol Rev. 2008;21(2):305- infected pulmonary infarction, and the radio- 33, table of contents. http://doi.org/dq4kf8. logical difficulty to differentiate bacterial pneu- 3. Miniati M, Bottai M, Ciccotosto C, Rober- monia and pulmonary infarction (11). In addi- to L, Monti S. Predictors of Pulmonary Infarc- tion, antibiotic treatment was selected based tion. Medicine (Baltimore). 2015;94(41):e1488. on the extrapolation of the local guidelines for http://doi.org/f3pjf5. the treatment of nosocomial pneumonia. Fur- 4. Morgenthaler TI, Ryu JH, Utz JP. Cavitary Pul- ther research on the subject is necessary to monary Infarct in Immunocompromised Hosts. Mayo better understand, diagnose, treat and prevent Clin Proc. 1995;70(1):66-8. http://doi.org/dzxf35. case reports

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