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Hot in the Tropics CLINICAL CARE CONUNDRUMS Hot in the Tropics The approach to clinical conundrums by an expert clinician is revealed through the presentation of an actual patient’s case in an approach typical of a morning report. Similarly to patient care, sequential pieces of information are provided to the clinician, who is unfamiliar with the case. The focus is on the thought processes of both the clinical team caring for the patient and the discussant. This icon represents the patient’s case. Each paragraph that follows represents the discussant’s thoughts Arpana R. Vidyarthi, MD1,2*, Gurpreet Dhaliwal, MD3,4, Bradley Monash, MD3, Koin Lon Shum, MD5, Joanne Lee, MBBS6, Aimee K. Zaas, MD, MHS7 1Duke-NUS Graduate Medical School, Singapore; 2Department of Medicine, National University Health System, Singapore; 3Department of Medi- cine, University of California, San Francisco, California; 4Medical Service, San Francisco VA Medical Center, San Francisco, California; 5Department of Internal Medicine, Singapore General Hospital, Singapore; 6Department of Haematology-Oncology, National University Cancer Institute, Singapore; 7Department of Medicine, Duke University School of Medicine, Durham, North Carolina. A 42-year-old Malaysian construction worker with 207,000/μL. Serum chemistries were normal. C-reactive subjective fevers of 4 days’ duration presented to an protein (CRP) level was 44.6 mg/L (reference range, 0.2- emergency department in Singapore. He reported nonpro- 9.1 mg/L), and procalcitonin level was 0.13 ng/mL (refer- ductive cough, chills without rigors, sore throat, and body ence range, <0.50 ng/mL). Chest radiograph was normal. aches. He denied sick contacts. Past medical history in- Dengue antibodies (immunoglobulin M, immunoglobulin G cluded chronic hepatitis B virus (HBV) infection. The [IgG]) and dengue NS1 antigen were negative. The patient patient was not taking any medications. was discharged with a presumptive diagnosis of viral upper respiratory tract infection. For this patient presenting acutely with subjective fevers, nonproductive cough, chills, aches, and lethargy, initial There is no left shift characteristic of bacterial infection or considerations include infection with a common virus (in- lymphopenia characteristic of rickettsial disease or acute fluenza virus, adenovirus, Epstein-Barr virus [EBV]), acute HIV infection. The serologic testing and the patient’s over- human immunodeficiency virus (HIV) infection, emerging all appearance make dengue unlikely. The low procalci- infection (severe acute respiratory syndrome [SARS], Mid- tonin supports a nonbacterial cause of illness. CRP eleva- dle Eastern respiratory syndrome coronavirus [MERS-CoV] tion may indicate an inflammatory process and is relatively infection, avian influenza), and tropical infection (dengue, nonspecific. chikungunya). Also possible are bacterial infections (eg, with Salmonella typhi or Rickettsia or Mycoplasma species), Myalgias, pharyngitis, and cough improved over several parasitic infections (eg, malaria), and noninfectious illnesses days, but fevers persisted, and a rash developed over (eg, autoimmune diseases, thyroiditis, acute leukemia, envi- the lower abdomen. The patient returned to the emergen- ronmental exposures). cy department and was admitted. He denied weight loss and night sweats. He had multiple female sexual partners, The patient’s temperature was 38.5°C; blood pres- including commercial sex workers, within the previous 6 sure, 133/73 mm Hg; heart rate, 95 beats per minute; months. Temperature was 38.5°C. The posterior orophar- respiratory rate, 18 breaths per minute; and oxygen satu- ynx was slightly erythematous. There was no lymphade- ration, 100% on ambient air. On physical examination, he nopathy. Firm, mildly erythematous macules were present appeared comfortable, and heart, lung, abdomen, skin, and on the anterior abdominal wall (Figure 1). The rest of the extremities were normal. Laboratory test results included physical examination was normal. white blood cell (WBC) count, 4400/μL (with normal dif- Laboratory testing revealed WBC count, 5800/μL (75% ferential); hemoglobin, 16.1 g/dL; and platelet count, neutrophils, 19% lymphocytes, 3% monocytes, 2% atyp- ical mononuclear cells); hemoglobin, 16.3 g/dL; platelet count, 185,000/μL; sodium, 131 mmol/L; potassium, 3.4 *Address for correspondence and reprint requests: Arpana R. Vidyarthi, mmol/L; creatinine, 0.9 mg/dL; albumin, 3.2 g/dL; alanine MD, Division of Advanced Internal Medicine, Department of Medicine, NUHS Tower Block, Level 10, National University Health System, 1E Kent Ridge Rd, aminotransferase (ALT), 99 U/L; aspartate aminotrans- Singapore 119228; Telephone: +65-9009-8011; Fax: +65-6872-4130; E-mail: ferase (AST), 137 U/L; alkaline phosphatase (ALP), 63 [email protected] U/L; and total bilirubin, 1.9 mg/dL. Prothrombin time Received: May 8, 2016; Revised: October 13, 2016; Accepted: October 18, was 11.1 seconds; partial thromboplastin time, 36.1 sec- 2016 onds; erythrocyte sedimentation rate, 14 mm/h; and CRP, 2017 Society of Hospital Medicine DOI 10.12788/jhm.2753 62.2 mg/L. 462 An Official Publication of the Society of Hospital Medicine Journal of Hospital Medicine Vol 12 | No 6 | June 2017 Hot in the Tropics | Vidyarthi et al PCR for HIV would be positive at a high level in acute HIV. The skin biopsy is not characteristic of Sweet syndrome, which typically shows neutrophilic infiltrate without leuko- cytoclastic vasculitis, or of syphilis, which typically shows a plasma cell infiltrate. The patient’s erythematous oropharynx may indicate re- cent streptococcal pharyngitis. The fevers, elevated ASO titer, and CRP level are consistent with acute rheumatic fe- ver, but arthritis, carditis, and neurologic manifestations are lacking. Erythema marginatum manifests on the trunk and limbs as macules or papules with central clearing as the lesions spread outward—and differs from the patient’s rash, which is firm and restricted to the abdominal wall. Fevers persisted through hospital day 7. The WBC count was 1100/μL (75.7% neutrophils, 22.5% lym- phocytes), hemoglobin was 10.3 g/dL, and platelet count was 52,000/μL. Additional laboratory test results includ- ed ALP, 234 U/L; ALT, 250 U/L; AST, 459 U/L; lactate dehydrogenase, 2303 U/L (reference range, 222-454 U/L); and ferritin, 14,964 ng/mL (reference range, 47- 452 ng/mL). The duration of illness and negative diagnostic tests for in- FIG. 1. Skin lesions on abdominal wall. fections increases suspicion for a noninfectious illness. Con- ditions commonly associated with marked hyperferritinemia include adult-onset Still disease (AOSD) and hemophago- EBV, acute HIV, and cytomegalovirus infections often present cytic lymphohistiocytosis (HLH). Of the 9 AOSD diagnostic with adenopathy, which is absent here. Disseminated gonococcal (Yamaguchi) criteria, 5 are met in this case: fever, rash, sore infection can manifest with fever, body aches, and rash, but his throat, abnormal liver function tests, and negative rheumato- rash and the absence of penile discharge, migratory arthritis, and logic tests. However, the patient lacks arthritis, leukocytosis, enthesitis are not characteristic. Mycoplasma infection can pres- lymphadenopathy, and hepatosplenomegaly. Except for the ent with macules, urticaria, or erythema multiforme. Rickettsia elevated ferritin, the AOSD criteria overlap substantially illnesses typically cause vasculitis with progression to petechiae with the criteria for acute rheumatic fever, and still require or purpura resulting from endothelial damage. Patients with sec- that infections be adequately excluded. HLH, a state of abnor- ondary syphilis may have widespread macular lesions, and the ac- mal immune activation with resultant organ dysfunction, can companying syphilitic hepatitis often manifests with elevations be a primary disorder, but in adults more often is secondary to in ALP instead of ALT and AST. The mild elevation in ALT and underlying infectious, autoimmune, or malignant (often lym- AST can occur with many systemic viral infections. Sweet syn- phoma) conditions. Elevated ferritin, cytopenias, elevated drome may manifest with febrile illness and rash, but the acuity ALT and AST, elevated CRP and erythrocyte sedimentation of this patient’s illness and the rapid evolution favor infection. rate, and elevated lactate dehydrogenase are consistent with HLH. The HLH diagnosis can be more firmly established with The patient’s fevers (35°-40°C) continued without the more specific findings of hypertriglyceridemia, hypofibrin- pattern over the next 3 days. Blood and urine cultures ogenemia, and elevated soluble CD25 level. The histopatho- were negative. Polymerase chain reaction (PCR) test of logic finding of hemophagocytosis in the bone marrow, lymph the nasal mucosa was negative for respiratory viruses. nodes, or liver may further support the diagnosis of HLH. PCR blood tests for EBV, HIV-1, and cytomegalovirus were also negative. Antistreptolysin O (ASO) titer was 400 Rash and fevers persisted. Hepatitis A, hepatitis C, IU/mm (reference range, <200 IU/mm). Antinuclear anti- Rickettsia IgG, Burkholderia pseudomallei (the caus- bodies were negative, and rheumatoid factor was 12.4 U/mL ative organism of melioidosis), and Leptospira serologies, as (reference range, <10.3 U/mL). Computed tomography well as PCR for herpes simplex virus and parvovirus, were (CT) of the thorax, abdomen, and pelvis was normal. Re- all negative. Hepatitis B viral load was 962 IU/mL (2.98 sults of a biopsy of
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