Age: 1.0
Sex: M
Vaccine: MMR
Symptoms: Febrile neutropenia, Flow cytometry, Full blood count abnormal, Gene mutation, Gene mutation identification test
Clinical narrative: This literature marketed report has been received from the authors of a published article, and refers to a 14-month-old male patient.  The patient's concurrent conditions, medical history and concomitant medications were not reported.  On an unknown date, the patient was vaccinated with the first dose of measles, mumps, and rubella (wistar ra 27-3) virus vaccine, live (M-M-R II).  The patient presented with an asymptomatic, papularpustular rash on arms, legs, buttocks, face, and ear that developed 2 weeks after his 12-month measles, mumps, and rubella (wistar ra 27-3) virus vaccine, live (M-M-R II) vaccinations. A biopsy done at an outside institution revealed a necrotizing granulomatous infiltrate. He was treated with erythromycin and the lesions resolved over the ensuing 2 months. Following his next round of vaccinations at 24 months, the lesions recurred and the patient presented to their dermatology department for evaluation. A biopsy was taken. Histologic sections revealed a cup-shaped depression of the epidermis, which exhibited perforation with necrobiotic collagen. The dermis showed necrobiosis with palisading histiocytes and a lymphoplasmacytic inflammatory cell infiltrate. An Alcian-blue special stain revealed focal increased dermal mucin. A differential diagnosis of perforating granuloma annulare, infection, or rheumatoid nodule was considered. Laboratory tests showed mildly elevated triglycerides (211 mg/dL; reference range: less than 150 mg/dL). The patient was treated with clobetasol (0.05 %) and topical tacrolimus (0.1 %). At the two-month follow-up, the patient's family reported rare flares and improvement of his rash with residual pitted scars. At the four-month follow-up, the family reported that they had stopped using the medication and the patient had experienced a couple of flares. A repeat biopsy of a new lesion on his arm was performed and showed similar findings to the previous biopsy. There were numerous granulomas, many of which showed necrobiosis, surrounded by a lymphoplasmacytic infiltrate. On an unknown date, the patient was vaccinated with the second dose of measles, mumps, and rubella (wistar ra 27-3) virus vaccine, live (M-M-R II). At the age of 4 years, the patient presented to our emergency department with 5 days of fever (up to 102.3 degrees Fahrenheit), chills, diaphoresis, fatigue, and pallor, 3 weeks after his measles, mumps, and rubella (wistar ra 27-3) virus vaccine, live (M-M-R II). On physical examination, hepatosplenomegaly was noted; skin examination was normal with the exception of residual pitted scars. A complete blood count showed pancytopenia and the patient was treated with cefepime (50 mg/kg) for neutropenic fever and a red blood cell transfusion for anemia. Imaging tests confirmed hepatosplenomegaly, but no lymphadenopathy. A bone marrow biopsy revealed a hypercellular marrow with maturing trilineage hematopoiesis. Ferritin was elevated (2059 ng/mL, reference range: 20250 ng/mL), as well as triglycerides (374 mg/dL, reference range, 150 mg/dL), and soluble interleukin-2 (IL-2) receptor (3458 U/mL, reference range: 02234 U/mL). Hemophagocytic lymphohistiocytosis was considered and next generation sequencing panels and flow cytometry-based assays were performed at a reference laboratory on a blood sample. Flow cytometry assays showed increased perforin expression and mean channel fluorescence of granzyme B in natural killer cells. CXCL9 level was elevated. The patient was treated with anakinra (2 mg/kg) for possible immune dysregulation disorder of unclear etiology without response. He continued to exhibit persistent pancytopenia, fluctuating inflammatory markers, and recurrent fevers. He was treated with dexamethasone (10 mg/m2) daily for 14 days. After a week, he was readmitted with fluctuating fever (up to 107.8 degrees Fahrenheit). Laboratory studies showed continued pancytopenia, elevated liver enzymes (alanine aminotransferase (ALT) was 1656 U/L, normal range: 0-50 U/L; aspartate aminotransferase (AST) was 951, normal range: 0-50 U/L; total bilirubin was 1.6 mg/dL, normal range: 0-1.2 mg/dL) and high ferritin (5941 ng/mL, normal range: 20-250 ng/mL) and triglyceride levels (662 mg/dL, normal range: less than 150 mg/dL). Abdominal ultrasound showed diffuse, coarse, and heterogeneous hepatomegaly suggestive of an infiltrative process. Bone marrow biopsy was repeated and showed multilineage dysplasia with increased (8 %) blasts without evidence of hemophagocytosis. A liver biopsy showed mild-to-moderate portal inflammation and periportal hepatitis with piecemeal necrosis. Mild lobular degeneration with small non-necrotizing granulomas and mild fibrosis were seen. Overall, modified hepatitis activity index was 3-4/18. Next generation sequencing panels revealed 2 probable disease-causing mutations on UNC13D. A diagnosis of haemophagocytic lymphohistiocytosis (HLH) (familial haemophagocytic lymphohistiocytosis) was made and he was transferred to an outside institution with an HLH center for further evaluation and allogeneic bone marrow transplant.  The outcome of familial haemophagocytic lymphohistiocytosis was unknown.  The reporter considered familial haemophagocytic lymphohistiocytosis to be related to the vaccine.