ABSTRACT
Severe combined immunodeficiency is a large clinically heterogeneous group of disorders caused by a defect in the development of humoral or cellular immune responses. At least 13 genes are known to be involved in the pathophysiology of the disease and the mutation spectrum in SCID has been well documented. Mutations of the recombination-activating genes RAG 1 and RAG 2 are associated with a range of clinical presentations including, severe combined immunodeficiency and autoimmunity. Recently, our understanding of the molecular basis of immune dysfunction in RAG deficiency has improved tremendously with newer insights into the ultrastructure of the RAG complex. In this report, we describe the application of whole exome sequencing for arriving at a molecular diagnosis in a child suffering from B- T- NK+ severe combined immunodeficiency. Apart from making the accurate molecular diagnosis, we also add a genetic variation c.2308G>A p.E770K to the compendium of variations associated with the disease.
ABSTRACT
BACKGROUND: Chikungunya (CHIK) is an emerging viral disease with a myriad of cutaneous manifestations. AIMS: The aim of our study was to document the morphology and evolution of skin lesions in cases presenting with fever, purpuric macules and vesiculobullous lesions, to confirm its causative relationship with CHIK, and to investigate further in order to delineate possible mechanisms of bulla formation in these cases. MATERIALS AND METHODS: A prospective, descriptive hospital-based study was carried out at a tertiary health care centre in Kerala. A total of 10 patients were enrolled in the study and investigated. RESULTS: All cases had morbilliform eruption prior to onset of purpuric macules. Eight cases developed vesiculobullous lesions that arose either de novo or over a part or whole of the purpuric macules. Skin lesions resolved within an average of 7.6 days leaving post-inflammatory hypopigmentation. IgM CHIK enzyme-linked immunosorbent assay (ELISA) was positive in all 10 patients. Tzanck smear from the bullae showed lymphocytes in most cases along with acantholytic cells, necrotic keratinocytes or occasional neutrophils. Skin biopsy showed intraepidermal or subepidermal bullae. Immunohistochemistry revealed predominantly CD8 positive T lymphocytes in the infiltrate. The prognosis was good with supportive management alone. DISCUSSION: The clinical features in our cases are comparable to the 3 previous reports of vesiculobullous lesions in CHIK affected infants. Based on the current evidence, we hypothesize that at least 2 mechanisms are at play for these skin lesions; CHIK virus induced keratinocyte necrosis followed by a cytotoxic immune response, and possible modulation of rash by drugs. CONCLUSION: With severe epidemics of CHIK spreading from Asia and Africa to the Western hemisphere, we must consider bullous CHIK as a differential diagnosis in cases with fever and purpuric and vesiculobullous lesions.
