“ ” John B. Darby, MD,a​ Gregory Valentine, MD,​a Kirsty Hillier, MD,​a Raegan Hunt, MD, PhD,a,​ b​ AC. Mary 3-Week-Old Healy, MD,a​ Valeria Smith, MD,​a Wendy With Allen-Rhoades, an MDa Isolated Blueberry Muffin Rash abstract

A 3-week-old boy, former 39-week term infant, presented to the emergency department with a rash. One week before presentation, he developed dark, purple papules on his forehead, which then spread to the abdomen and inguinal regions. Throughout this time, he was eating well, gaining weight, developing appropriately, and was afebrile without cough, congestion, or rhinorrhea. On presentation, the patient was well appearing with normal vital signs. His weight was 4.83 kg (86th percentile for age), his length was 56 cm (47th percentile for age), and his head circumference was 37 cm (62nd percentile for age). On skin examination, there were scattered purpuric papules and macules on the scalp, forehead, trunk, abdomen, and inguinal Departments of aPediatrics and bDermatology, Baylor region. Initial laboratory studies were remarkable only for mild anemia. “ ” College of Medicine/Texas Children’s Hospital, Houston, Our expert panel examines the case, offers a differential for a child with a Texas blueberry muffin rash, and makes diagnostic considerations. Dr Darby contributed to the design and execution of the case conference and drafted and edited the Case History With Subspecialty original manuscript; Drs Valentine, Hillier, Hunt, Input ’ Healy, Smith, and Allen-Rhoades contributed to the or delivery. He passed his hearing design and execution of the case conference and Dr Gregory Valentine (Resident, Streptococcusscreen, and the mother s serologies reviewed the manuscript; and all authors made Pediatrics, Global Child Health) were negative, including group B revisions to the manuscript and approved the final . Additionally, both manuscript. newborn screens were normal, and DOI: https://​doi.​org/​10.​1542/​peds.​2016-​2598 A 3-week-old boy, former 39-week he received the hepatitis B vaccine at Accepted for publication Jan 31, 2017 term infant, presented to the birth. Address correspondence to John B. Darby, MD, emergency department (ED) with a The patient had 2 healthy older Department of Pediatrics, Baylor College of rash. One week before presentation, Medicine/Texas Children’s Hospital, 1102 Bates siblings who did not have a similar Street, #FC1860, Houston, TX 77030. E-mail: jbdarby@ he developed dark, purple papules rash in the first few months of their texaschildrens.org on his forehead, which then spread lives. The family had not traveled to PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, to the abdomen and inguinal regions. any other country since his birth, and 1098-4275). Over the course of a week, the rash there were no animal exposures. The Copyright © 2017 by the American Academy of continued to spread and appeared to patient was seen by his pediatrician on Pediatrics be on the extremities, abdomen, and the day of presentation, who referred FINANCIAL DISCLOSURE: The authors have head, which prompted presentation him to be evaluated in the ED. indicated they have no financial relationships to the ED. From the time of onset of relevant to this article to disclose. In the ED, the patient was well the rash to the presentation at the ED, ° appearing with a temperature of FUNDING: No external funding. he was eating well, gaining weight, 98.0 F, a pulse of 156 beats per minute, POTENTIAL CONFLICT OF INTEREST: The authors developing appropriately, and had blood pressure of 87/52 mmHg, and have indicated they no potential conflicts of interest remained afebrile without cough, to disclose. a respiratory rate of 40 breaths per congestion, or rhinorrhea. minute. His weight was 4.83 kg (86th Regarding birth history, the patient percentile for age), his length was To cite: Darby JB, Valentine G, Hillier K, et al. A was born to a gravida 3 para 3 mother 56 cm (47th percentile for age), and 3-Week-Old With an Isolated “Blueberry Muffin” who had prenatal care beginning in his head circumference was 37 cm Rash. Pediatrics. 2017;140(1):e20162598 the first trimester and no reported (62nd percentile for age). He was in no complications during pregnancy acute distress. He had no discernible Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 140, number 1, July 2017:e20162598 DIAGNOSTIC DILEMMAS petechiae, but he had scattered, (hemangiomatosis, blue rubber bleb ecchymotic, purpuric papules and nevus syndrome). macules on the scalp, forehead, trunk, Cytomegalovirus (CMV) is the most abdomen, and inguinal region (Figs 1 common congenital infection and ’ and 2). can cause a petechial rash due to Results of the patient s laboratory thrombocytopenia. Congenital evaluation are shown in Table 1. toxoplasmosis has been described They are notable for a mild anemia with this type of rash, but it is a rare but otherwise are unremarkable. infection in the United States. Syphilis Cerebral spinal fluid studies, liver isDr another Darby possibility. function tests, chest radiograph, and coagulation studies were interpreted as normal. A head ultrasound was Dr Cabrera-Meza mentioned several significant for visualization of infectious causes of a purpuric lenticulostriate vessels, consistent FIGURE 2 rash. With TORCH infections, do with mineralizing vasculopathy, a Skin findings. you typically see a purpuric rash nonspecific finding that can presenting at birth or several weeks be seen with in utero infection. later?Dr Mary Healy (Pediatric Infectious The patient was admitted for Disease) additional evaluation and occurs because of extramedullary hematopoiesis in sites of different management.Dr John Darby (Moderator, Pediatric Hospital Medicine) magnitudes and extensions. Since then, the differential diagnosis In an infant with a purpuric rash, as associated with this type of rash mentioned by Dr Cabrera-Meza, you “ ” has been broadened significantly. need to think broadly because some Does this patient qualify as having The differential includes the infections presenting with this type a blueberry muffin rash and, if so, following: infectious etiologies, such of rash need to be treated promptly. Drwhat Gerardo is the differentialCabrera-Meza diagnosis? However, in this case, the infant has as toxoplasmosis, other (syphilis, (Neonatology) been perfectly well until this point, varicella-zoster, parvovirus B19), and the rash did not develop until rubella, cytomegalovirus, and herpes several weeks after birth. This makes (TORCH) infections (especially Yes, the description is consistent TORCH infections less likely, but not congenital rubella), blood with a blueberry muffin rash. impossible. dyscrasias (ABO incompatibility, The term originated in the early Rh incompatibility, minor Without the history above, the 1960s when the rubella epidemic group incompatibility, twin-to- appearance of the rash alone would occurred in this country. This rash twin transfusion syndrome), lead me to consider the blueberry malignancies (congenital leukemia, muffin rash characteristic of Langerhans cell histiocytosis [LCH], congenital rubella syndrome (CRS). TAneuroblastoma),BLE 1 ED Laboratory and Evaluation skin disorders However, CRS is rare in the United Variable Reference Range Laboratory Test Results WBC count, 103 cells/μL 9.1–34 16.46 Differential, % Segmented neutrophils 32–67 19.8 Lymphocytes 25–37 50.4 Bands 0–8 7.4 Hemoglobin, g/dL 15.0–22.0 13.0 Platelet count, 103 cells/μL 150–450 327 INR 0.8–1.2 1.2 PT, sec 10.4–15.0 14.1 PTT, sec 24.9–34.1 47.5 LDH, U/L 500–920 2014 Uric acid, mg/dL 2.0–6.2 2.4 FIGURE 1 INR, international normalized ratio; LDH, lactate dehydrogenase; PT, prothrombin time; PTT, partial thromboplastin time; Skin findings. WBC, white blood cell.

Downloaded from www.aappublications.org/news by guest on September 25, 2021 2 Darby et al States and in other developed later when they present with, for CMV include small for gestational countries with high uptake of example, poor visual acuity early age, jaundice, hepatosplenomegaly, childhood vaccination. Between in childhood and are found to have neurologic manifestations, including 2004 and 2012, there were only 6 chorioretinitis, or perhaps hearing microcephaly and hypotonia, and reported cases to the Centers for1 problems or developmental delay. a rash. Pinpoint petechiae are Disease Control and Prevention. The cutaneous findings may be more characteristic of the rash – Virtually all of these cases were in diverse, including a maculopapular, of congenital CMV, rather than a infants of unimmunized mothers or blue, or petechial rash2 secondary to blueberry muffin type appearance. were imported cases, meaning that thrombocytopenia. It is noteworthy Also, thrombocytopenia is associated they were from people that were not that this infant had a normal platelet with this rash. immunized and came to the United count. ’ Although unlikely, congenital States from another country. Congenital syphilis could also present CMV should also be ruled out In this case, the infant s mother has with a rash at this age. However, the because neonates with symptomatic had 3 children all born within 5 to rash is typically different. Our patient congenital infection, with or 6 years of each other and has had did not have any rash on the palms without CNS involvement, medically attended deliveries in US or soles, and congenital syphilis does have improved hearing and hospitals each time with multiple not give you the typical blueberry neurodevelopmental outcomes at screenings for infectious diseases muffin type of rash. Cutaneous 2 years of age when treated with during each pregnancy. It is highly findings are usually maculopapular valganciclovir for 6 months. The unlikely she would have tested lesions prominent on the palms, American Academy of Pediatrics rubella nonimmune and not have soles, back, buttocks, and posterior does not recommend antiviral received the measles, mumps, rubella thighs, as well as vesiculobullous therapy for asymptomatic infants at vaccine postdelivery. lesions, starting as hyperpigmented this time, however, at a minimum, red papules and progressing to Also, the clinical presentation 3,4​ these infants should be monitored desquamation and crusting. ‍ of CRS is not subtle. There were for the development7 of hearing loss no other indications of CRS in It important to rule these infections Drover Darby time. this infant, specifically, there out, however, because left untreated, was no hepatosplenomegaly, no both infections can have severe chorioretinitis, no transaminitis, a and long-term sequelae, such as Oncologic causes of this rash were in history of a normal hearing screen, impairment of vision and hearing the differential diagnosis. What were and he was normocephalic. For these and developmental delay with your thoughts when you saw this reasons, despite the appearance of congenital toxoplasmosis and Drpatient? Wendy Allen-Rhoades (Pediatric the rash, I felt strongly that this was multiorgan involvement of the Oncology) notDr Darby going to be CRS. central nervous system (CNS), bones and joints, teeth, eyes, ears, and skin in congenital syphilis, some of which Oncologic diagnoses in a newborn And what about congenital may take decades to manifest. After are certainly rare, but they are toxoplasmosis or syphilis as treatment, both conditions require important to consider in this case. mentioned previously? Can they follow-up5,6​ to ensure relapses do not One of the most common oncologic Drpresent Healy like this? Droccur Darby. ‍ diagnoses in the newborn period that can present with a rash is congenital neuroblastoma. Furthermore, It is rare that we see the full And is congenital CMV a neuroblastoma is the most common “ ” clinical syndrome of congenital Drconsideration? Healy extracranial solid tumor in childhood toxoplasmosis because 80% and 4S is a special stage of to 90% of infected infants are neuroblastoma in infants <1 year of asymptomatic at birth. The classic After examining this infant, I felt age with metastases limited to the8 presentation is a triad of intracranial that congenital CMV was unlikely. liver, bone marrow, and/or skin. The calcifications, chorioretinitis, and In common with congenital rash secondary to skin metastases in hydrocephalus, which may occur toxoplasmosis, the majority of neuroblastoma typically consists of if a mother is infected early in the congenital CMV infections are generalized, scattered, small (<2 cm), pregnancy. However, this is rare. subclinical at birth or in the firm, nontender blue, red, or purple

The vast majority of these patients neonatal period. When present, papules and/or9 mobile subcutaneous are diagnosed months or years symptoms and signs of congenital nodules. Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 140, number 1, July 2017 3 Adrenal and hepatic neuroblastoma remains broad. Dr Hunt, are there has been associated with congenital lesions can be incidentally detected dermatologic conditions we should infections, neonatal lupus, as well as on routine prenatal ultrasounds. consider, and can you help us narrow intrauterine exposures and genetic

These incidentally noted lesions the possibilities at all based on the conditions, but11 not with neonatal in neonates can usually be features of this skin rash? malignancies. As mentioned, ’ Dr Raegan Hunt (Pediatric monitored postnatally, under an initially there was concern for a Dermatology) ’ oncologist s supervision, with TORCH infection based on the skin serial ultrasounds, and many findings, but it didn t seem to fit of them self-resolve without ’ well because the child was healthy It is hard to narrow the differential treatment. However, sometimes appearing, had good prenatal care, “ ” diagnosis based on this patient s ∼ the lesions progress or are too and the skin lesions were not present skin exam alone. I agree that the 2- large for watchful waiting and until 3 weeks of life. Unusual to 10-mm, nonblanching, magenta- require a biopsy and/or resection purpuric variants of neonatal lupus to-violaceous macules and thin with subsequent chemotherapy have been reported, and neonatal papules seen in this patient are treatment. Additionally, some lupus tends to manifest with lesions consistent with a blueberry muffin patients who have liver involvement concentrated around the face and rash. Regarding the differential can become ill quickly and require scalp a few weeks to months after diagnosis previously discussed, the 12 prompt therapy. Overall, however, birth. For these reasons, we thought individual lesions are not as sharply most patients with neuroblastoma it was reasonable to consider a circumscribed and not as intensely in the neonatal period do well, even purpuric variant of neonatal lupus in red or purple, respectively, as those with metastases to those restricted addition to the traditional blueberry typically seen in hemangiomatosis sites. The mother did not recall any muffin rash differential diagnosis. or blue rubber bleb nevus syndrome. specific mention of abnormalities Clinical speculating aside, we felt that Due to its clinical appearance, the ’ on prenatal ultrasounds, and a skin biopsy was important to help blueberry muffin rash is included an abdominal ultrasound was diagnose this infant s rash. in the broad category of neonatal Dr Darby performed to evaluate the adrenal purpura, yet, in contrast to glands and liver. traditional purpuric skin disorders Leukemia cutis, which is leukemia caused by extravasation of red Neonatal lupus was mentioned. in the skin, is another oncologic blood cells into the skin, in Infants with neonatal lupus have diagnosis that can present with a blueberry muffin rash cases, the ’ antibodies that are transmitted from skin rash in the newborn period. purpuric-to-violaceous appearance the mother. Our patient s mother Although the blood counts and is due to either extramedullary denied major illnesses. Is this peripheral smear were normal in hematopoiesis in the skin or common? this patient except for a mild anemia, metastatic dermal infiltration10 of Dr Eyal Muscal (Pediatric it does not rule out leukemia. It is malignant neoplastic cells. This Rheumatology) not uncommon to have relatively patient had numerous flat-to-mildly normal counts early in the course indurated, small skin lesions. This of acute leukemia. Additionally, the eruption localized mostly to the face presence of peripheral blasts is not and scalp and involved the trunk Over 50% to 60% of mothers do not necessary to make a diagnosis of to a lesser extent. Remarkably, the have a rheumatologic illness at the leukemia, because the bone marrow extremities were spared in this time of their infants being diagnosed can be involved with blasts without child. The classic description of a with neonatal lupus. It is important spillage into the peripheral blood. blueberry muffin rash in a TORCH to note that the condition is self- Finally, LCH, a rare histiocytic infection has more widespread limited in infants and improvement disorder, can present in a multitude lesions. In addition, malignancy- is seen once the maternal antibodies of ways, including various skin related skin metastases in a dissipate in 4 to 6 months. The skin findings. Specifically, infants newborn blueberry muffin rash are lesions are typically annular and may present with skin lesions typically described as firmer, larger, can be scaly and erythematous. that are brownish purple papules and fewer. When these infants go out into the sun, they may develop a rash that ofDr theDarby skin. Unfortunately, no clues led to a percolates. certain diagnosis. Interestingly, ’ lenticulostriate vasculopathy was Other features of neonatal lupus So, we ve considered infectious and found on head ultrasound. This is a include congenital heart block, oncologic causes and the differential nonspecific CNS imaging finding that transaminitis, and cytopenias. Downloaded from www.aappublications.org/news by guest on September 25, 2021 4 Darby et al TABLE 2 Laboratory Data Variable Reference Range Laboratory Test Results CMV qnPCR plasma 96–1.88 × 108 IU/mL Not detected CMV qnPCR urine 475–1.88 × 108 IU/mL Not detected CMV qnPCR CSF 142–1.88 × 108 IU/mL Not detected Viral culture CSF N/A No virus isolated Enterovirus PCR CSF Not detected RNA not detected VDRL Qual CSF Nonreactive Nonreactive Protein CSF <100 mg/dL 74 Glucose CSF 50%–70% serum glucose mg/dL 46 Culture CSF N/A No growth 3 3 3 Cell count CSF WBC, 0–19/mm , 0%–4% 16 WBC/mm , RBC 183/mm , 1% neutrophils, FIGURE 3 neutrophils, 17%–23% 36% lymphocytes, 53% monocytes Pathology findings. Skin biopsy shows solid lymphocytes sheets of blue cells diffusely infiltrating the RPR, blood Nonreactive Nonreactive dermis and subcutaneous adipose tissue, sparing MHA TPa Nonreactive Nonreactive the epidermis (hematoxylin and eosin stain, HIV Ab/Ag Negative, negative Nonreactive, negative original magnification× 20). combination, HIV Ab ELISA HSV 1/2 IgM Ab ≤0.89 IV 0.26 IV HSV 1/2 IgG Ab ≤0.89 IV >22.40 IV CMV IgG Ab ≤0.59 U/mL 4.50 U/mL this patient, and results were finally Varicella IgM ≤0.90 ISR 0.02 obtained. What did it show under the Rubella IgM ≤19.9 AU/mL <10.0 Drmicroscope? Kalyani Patel (Pediatric Toxoplasma IgM <8.0 AU/mL <3.0 Toxoplasma IgG <7.2 IU/mL <3.0 Pathology) Ab, antibody; Ag, antigen; CSF, cerebral spinal fluid; ELISA, enzyme-linked immunosorbent assay; HIV, human immunodeficiency virus; HSV, herpes simplex virus; qnPCR, quantitative polymerase chain reaction; RBC, red blood cell; RPR, rapid plasma reagin; VDRL Qual, venereal research disease laboratory qualitative; WBC, white blood cell. On low-power view, the entire a Microhemagglutination assay for Treponema pallidum antibody. dermis and superficial subcutaneous fat are infiltrated by sheets of fairly monotonous and atypical You can evaluate this diagnosis by or adrenal lesions. An anti-nuclear blue cells (Fig 3). Immediately, sending lupus spectrum antibodies, antibody panel and testing for other a malignancy was highest on ö ’ such as immunoglobulin (Ig)G rheumatologic antibodies were my differential. Extramedullary Sj gren s syndrome autoantibodies negative. Vanillylmandelic acid hematopoiesis can be a mimic, (SSA [ro] SSB [La]), liver, and blood (VMA) and homovanillic acid (HVA) but is usually well organized and counts, and take a careful maternal samples were sent as well, which noninfiltrative. history. As mentioned, however, returned negative. High-power examination shows many mothers may not have solid sheets of large cells with a Can you comment on why VMA and a history of a rheumatologic high nucleus to cytoplasm ratio, HVA samples were sent for this Drdisease. Darby irregular nuclear contours, fine patient?Dr Allen-Rhoades chromatin, prominent nucleoli, and scattered hyperchromasia. While on the pediatric hospital Cytoplasmic borders are indistinct, medicine service, laboratories, Urine catecholamines (VMA or giving a syncytial appearance (Fig 4). imaging, and skin biopsy were HVA) are used as a biomarker for Several apoptotic bodies and mitotic obtained for diagnostic evaluation. neuroblastoma. Approximately figures are seen, which is indicative Infectious serologies are listed 80% to 90% of patients with of a high proliferative index. The in Table 2 and were negative. In neuroblastoma will have elevated nuclear features are not typical addition, a skeletal survey was urine VMA or HVA due to secretion for a small-round blue cell tumor, normal. Liver function tests were of the catecholamine13 byproducts by such as neuroblastoma, that has ’ normal, and a peripheral blood the tumor. Thus, if it is positive, stippled chromatin and a spectrum smear showed no hematologic it is nearly pathognomonic for of ganglionic differentiation. Ewing s malignancy. As noted in Table 1, neuroblastoma, but the negative sarcoma is a possibility, but it is there was a normal uric acid Drresult Darby does not rule it out. less likely in the absence of a mass level, but lactate dehydrogenase elsewhere. The placenta was not was elevated to 2014 IU/L. An available in this case to evaluate for abdominal ultrasound was normal As Dr Hunt suggested, a skin biopsy the presence of these atypical cells in and without hepatosplenomegaly was important diagnostically for the fetal vessels. Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 140, number 1, July 2017 5 (AML) when accounting16 for all extramedullary sites. It can occur de novo without AML or concurrently with AML. It can present several months to years before bone marrow evidence of leukemia, or it can be the first sign of relapse of leukemia. In our patient, a bone marrow biopsy FIGURE 4 was done that revealed 43% of cells Pathology findings. Skin biopsy: cells are large were myeloid blasts and confirmed with irregular oval nuclei, immature chromatin, a diagnosis of AML with cutaneous prominent nucleoli, scant pale cytoplasm, and syncytial appearance (hematoxylin and eosin, myeloidDr Darby sarcomas. original magnification× 600).

How does bone marrow involvement Dr Darby affect the treatment and prognosis of Drthis Smith condition? Are there other staining techniques to help us determine the type of The treatment is the same Drneoplasm? Patel regardless of bone marrow involvement. Myeloid sarcoma was once felt to be more aggressive than Yes. The tumor cells were positive for traditional AML; however, we now myeloperoxidase and CD43 (Fig 5 A believe that the specific biology of and B) which is essentially diagnostic the particular AML subtype is more of myeloid blasts and a myeloid important for prognosis than the sarcoma. Diffuse positivity for CD68 FIGURE 5 presence of myeloid sarcomas. Pathology findings. A subset of tumor cells show (PGM1 clone) was suggestive of The standard AML treatment monocytic differentiation and the cytoplasmic positivity for myeloperoxidase (A, original magnification× 200), diffuse and strong is intensive chemotherapy M5 subcategory (Fig 5C). Tumor reactivity for CD43 (B, original magnification with possible bone marrow cells were negative for terminal ×40), along with diffuse cytoplasmic expression transplantation (which is for CD68, PGM1 clone (C, original magnification deoxynucleotidyl transferase determined by biological factors ×200). (lymphoblasts), CD1a (LCH), CD3 and response to therapy). We have and CD5 (T-cell markers), Pax 5 seen great improvements in the (B-cell marker), CD30 (anaplastic overall survival of patients with large cell lymphoma), tryptase (mast ’ “ ” AML in the last 30 years, and the cells), NB84a (neuroblastoma), the early 19th century, and, at that 17 rate has doubled to nearly 65%. CD99 (Ewing s sarcoma), and time, they were termed chloromas due to the green tumor appearance. However, AML in infants often acts pancytokeratin (epithelial “ ” Later, the term was changed to differently it does in older children, malignancy).Dr Darby granulocytic sarcoma after several and the 18course can be difficult to cases that lacked the green color Drpredict Darby.

of the tissue specimen, and they15 This case is an interesting case of appeared more like a sarcoma. myeloid sarcoma. Can you tell us However, because we now know that What are common signs and Drmore Valeria about Smith this diagnosis? (Pediatric not all myeloid leukemias are derived symptoms to help evaluate for Hematology and Oncology) from granulocytes, the preferred leukemia in general pediatrics term is myeloid sarcoma. Myeloid Drpractice? Smith sarcoma can be single or multifocal Myeloid sarcoma is a rare neoplastic and can be found in the skin, soft condition consisting of immature tissue, bone, lymph nodes, and, less Leukemia, in general, is the most ∼ ∼ myeloid cells that form14 a tumor in commonly, the intestine, eyes, and common childhood cancer. With an extramedullary site. Myeloid mediastinum. It occurs in 11% of regard to AML, 730 new cases are sarcomas were first described in patients with acute myeloid leukemia diagnosed each year in the United Downloaded from www.aappublications.org/news by guest on September 25, 2021 6 Darby et al 30th ed. American Academy of Abbreviations 19 Pediatrics; 2015:317–322 States in patients <20 years of age. 8. Brodeur GM, Hogarty MD, Bagatell R, Children with AML will typically Mosse YP, Maris JM. Neuroblastoma. present with some combination of AML: acute myeloid leukemia In: Pizzo PA, Poplack DG, eds. Principles the following: fever, fatigue, pain, CMV: cytomegalovirus and Practice of Pediatric Oncology. 7th pallor, weight loss, bony pain, CNS: central nervous system ed. Philadelphia, PA: Wolters Kluwer; anorexia, and malaise. Physical CRS: congenital rubella syndrome 2016:772–797 examination findings can include ED: emergency department 9. Schwar tz RA. Cutaneous metastatic hepatosplenomegaly, excessive HVA: homovanillic acid disease. J Am Acad Dermatol. bruises (particularly areas that do Ig: immunoglobulin 1995;33(2 pt 1):161–182 not typically bruise), petechiae, or LCH: Langerhans cell 10. Baselga E, Drolet BA, Esterly NB. pallor. In an infant, the signs and histiocytosis Purpura in infants and children. J Am symptoms may be more difficult TORCH: toxoplasmosis, other Acad Dermatol. 1997;37(5 pt 1):673–705 to recognize and may be brought (syphilis, varicella-zos- 11. Wang HS, Kuo MF, Chang TC. to the attention of the physician ter, parvovirus B19), Sonographic lenticulostriate by the parent for poor feeding, rubella, cytomegalovi- vasculopathy in infants: some decreased activity, increased rus, and herpes associations and a hypothesis. AJNR fussiness, or prolonged fever VMA: vanillylmandelic acid Am J Neuroradiol. 1995;16(1):97–102 without a source. Physical References 12. Saoji V, Deopujari S. Neonatal lupus examination and laboratory erythematosus - three different findings may include an 1. McLean H, Redd S, Albernathy E, presentations. Indian J Paediatr Icenogle J, Wallace G. Congenital Dermatol. 2014;15(3):110 113 abnormal complete blood count, – rubella syndrome. In: Roush SW, Baldy hepatosplenomegaly, petechiae, 13. Strenger V, Kerbl R, Dornbusch HJ, LM, eds. Manual for the Surveillance of et al. Diagnostic and prognostic and other rashes, as seen in this 17 Vaccine-Preventable Illnesses. Atlanta, impact of urinary catecholamines in caseDr Darby. GA: Centers for Disease Control and neuroblastoma patients. Pediatr Blood Prevention; 2014 Cancer. 2007;48(5):504–509 2. McLeod R, Remington JS. 14. Campidelli C, Agostinelli C, Stitson HowDr Judith is the Margolin patient doing? (Pediatric Toxoplasmosis (Toxoplasma gondii). R, Pileri SA. Myeloid sarcoma: Hematology and Oncology) In: Kliegman RM, Behrman RE, Jenson extramedullary manifestation of HB, Stanton BF, eds. Nelson Textbook of myeloid disorders. Am J Clin Pathol. Pediatrics. 18th ed. Philadelphia, PA: 2009;132(3):426–437 He is doing well. The rest of his Saunders; 2007:1486–1495 15. Bakst RL, Tallman MS, Douer D, workup revealed CNS disease, which 3. Benza N, Stankovic C. Visual diagnosis: Yahalom J. How I treat extramedullary means that leukemia cells were a 2-month-old boy with an unusual acute myeloid leukemia. Blood. present in the spinal fluid, and an rash. Pediatr Rev. 2015;36(12):e43–e46 2011;118(14):3785–3793 MRI of the brain showed leukemia 4. Dobson SR. Congenital syphilis: clinical 16. Dusenbery KE, Howells WB, Arthur infiltrates. He received the first cycle features and diagnosis. Available DC, et al. Extramedullary leukemia in of chemotherapy and experienced at: www.​uptodate.​com/​contents/​ children with newly diagnosed acute some anticipated side effects, such congenital-​syphilis-​clinical-​features-​ myeloid leukemia: a report from the as neutropenia and mucositis, and-diagnosis.​ Accessed June 23, 2016 Children’s Cancer Group. J Pediatr for which he received supportive 5. Syphilis. In: Kimberlin DW, Brady MT, Hematol Oncol. 2003;25(10):760–768 care. After 1 cycle, he had a partial Jackson M, Long SS, eds. Red Book: 17. Rabin KR, Gramatges MM, Margolin JF, response and subsequently went 2015 Report of the Committee on Poplack DG. Acute myeloid leukemia into complete remission after a Infectious Diseases. 30th ed. American and myelodysplastic syndrome. In: ’ second cycle of chemotherapy. He Academy of Pediatrics; 2015:755–768 Pizzo PA, Poplack DG, eds. Principles and Practice of Pediatric Oncology. 7th is now 6 months postcompletion 6. Toxoplasma gondii infections. In: ed. Philadelphia, PA: Wolters Kluwer; of all 4 cycles of chemotherapy and Kimberlin DW, Brady MT, Jackson M, 2016:463–497 remains in complete remission and Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 18. Felix CA, Lange BJ. Leukemia in infants. is meeting all of his developmental 30th ed. American Academy of Oncologist. 1999;4(3):225–240 milestones. Pediatrics; 2015:787–796 Acknowledgments 19. American Cancer Society. Cancer facts 7. Cytomegalovirus infection. In: & figures 2014. Available at: www.​cancer.​ Kimberlin DW, Brady MT, Jackson M, org/research/​ cancer-​ facts-​ statistics/​ ​ Long SS, eds. Red Book: 2015 Report of all-cancer-​ facts-​ figures/​ cancer-​ facts-​ ​ We thank Gerardo Cabrera-Meza, MD, the Committee on Infectious Diseases. figures-​2014.​html. Accessed May 17, 2016 Eyal Muscal, MD, Kalyani Patel, MD, and Judith Margolin, MD. Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 140, number 1, July 2017 7 A 3-Week-Old With an Isolated ''Blueberry Muffin'' Rash John B. Darby, Gregory Valentine, Kirsty Hillier, Raegan Hunt, C. Mary Healy, Valeria Smith and Wendy Allen-Rhoades Pediatrics 2017;140; DOI: 10.1542/peds.2016-2598 originally published online June 2, 2017;

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Downloaded from www.aappublications.org/news by guest on September 25, 2021 A 3-Week-Old With an Isolated ''Blueberry Muffin'' Rash John B. Darby, Gregory Valentine, Kirsty Hillier, Raegan Hunt, C. Mary Healy, Valeria Smith and Wendy Allen-Rhoades Pediatrics 2017;140; DOI: 10.1542/peds.2016-2598 originally published online June 2, 2017;

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