LATE ONSET PRIMARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS in AN INDIAN ADOLESCENT BOY during A PEAK of POST COVID-19 MULTISYSTEM INFLAMMATORY SYNDROME

Background: Familial Hemophagocytic lymphohistiocytosis (fHLH) categorized as FHL2 (PRF1), FHL3 (UNC13D), FHL4 (STX11), and FHL5 (STXBP2) encoding for Perforin, Munc13-4, Syntaxin11, and Syntaxin binding protein 2, respectively. There is limited information available about the clinical and mutational spectrum of FHL patients in Indian population. Objectives: To delineate clinical and laboratory features of late onset familial Hemophagocytic Lymphohistiocytosis. Methods: A 12-years-old well nourished sick looking boy, born to a non-consanguineous parents with normal birth, development and immunization history with uneventful past presented to us with 6 days history of high fever, cough, breathing difficulty and severe headache. He had occasional vomiting, abdominal pain, polyarthragia & chest pain from last 10 days. Mother also had given history of throat pain, backache & some non-specifc papular rashes over face before the onset of fever. His vitals were normal. Examination revealed faint diffuse fxed erythematous rash all over the body, pallor, icterus and hepatos-plenomegaly. Musculoskeletal examination was unremarkable. Lab evaluation revealed HB 8.9gm%, TLC 4700/cumm with neutrophils 40% and lymphocytes 56% with 8-9% activated lympocytes. Further evaluation showed low ESR 6mm/hr, fbrinogen 97mg% and albumin 2.2 gm% with elevated CRP 40mg/L, ferritin 2000ng/ml, LDH 658IU/L, SGPT 110IU/L, SGOT 221 IU/L, total bilirubin 6mg%, D-dimer 4355 ng:EFU/ml and Triglycerides 441mg%. His blood, urine, CSF and bone marrow cultures were sterile for endemic bacterial and viral infections in our area. His EBV PCR, CoVID RT PCR and CoVID antibody (Total & IgG) test were negative. His immunoglobulin leves were normal. HRCT Chest showed bilateral mild-moderate plural effusions, mild interstitial thickening in both the lower lobes, few fbrotic opacities & old areas of consolidation bilaterally. 2D echo showed mild pericardial effusion. Bone marrow examination showed Hypercellular marrow with iron depletion and occasional hemophagocytosis with CD8 T lymphocytes proliferation (55.2%) and double positive CD4 & CD8 (1.2%). He was initially commenced on supportive therapy, oxygen & intravenous antibiotics. In view of most probable non-infectious, non-malignant hemophagocytic lymphohistiocytosis, he was fnally given intravenous immunoglobulin (2gm/kg) and intravenous pulse methylprednisolone (30mg/kg). He responded well to above regimen within 3 days. He was discharged with tapering steroids over few weeks. Clinical exome by NGS revealed Homozygous Mutation in STXBP2 gene Intron 14, c.1280-1G>C (3' Splice Site) His parents has been counselled for hematopoietic stem cell transplantation and their decision is still pending. Results: We compared our patietnt with a reference to the largest Indian series of pediatric HLH1. Conclusion: Primary HLH type 5 can present frst time during childhood and adolescence. Any child presenting with unexplained HLH features should undergo genetic analysis irrespective of person's past and family history.

Viral exanthems Unravelling viral rashes

Common causes of viral exanthems in Australia include herpesviruses, enteroviruses, parvovirus B19, varicella, measles and rubella viruses and mosquito-borne alphaviruses. The cause can often be diagnosed clinically from the rash distribution and morphology, confirmed only when necessary with serological or PCR tests. Most viral exanthems are self-limiting, requiring supportive care alone.

COVID vaccine cutaneous reactions: a case series of six patients

In response to the COVID-19 pandemic, over 89 million doses of coronavirus vaccines have been administered so far in the UK. An increasing number of mucocutaneous reactions are being seen as a result of the vaccines. These reactions can vary, from pruritus to urticaria and angio-oedema (Robinson LB, Fu X, Hashimoto D et al. Incidence of cutaneous reactions after messenger RNA COVID-19 vaccines. JAMA Dermatol 2021;157: 1000-2). Its recognition is important, as a small proportion of patients can develop potentially life-threatening conditions. Furthermore, initial reactions can have consequences on subsequent vaccine doses. We carried out a retrospective review of patients referred to our dermatology service over a 4-month period (June-October 2021) and identified those with suspected mucocutaneous reactions secondary to COVID-19 vaccines. Six patients were identified, three woman and three men, with a mean age of 56 years. Mucocutaneous reactions seen included: extensive parapsoriasis, widespread blistering rash, urticaria, angio-oedema, lichenoid papular eruption and erythema multiforme. Three reactions occurred after the Pfizer vaccine, two after the AstraZeneca and one was not specified. Two patients were advised not to have further doses. The incidence of cutaneous reactions to the COVID-19 vaccines is estimated to be 4% (McMahon DE, Amerson E, Rosenbach M et al. Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: a registry-based study of 414 cases. J Am Acad Dermatol 2021;85: 46-55). It is important to increase awareness and knowledge of these reactions, to allow appropriate management, and informed discussion regarding the safety of further doses.