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Kawasaki disease (KD) is a medium vessel vasculitis that predominantly affects children below 5. Diagnosis of KD is based on the presence of characteristic clinical manifestations as there are no definite diagnostic laboratory investigations for the diagnosis of this disease. Presence of atypical clinical features such as myositis often pose diagnostic challenge for the treating physicians. Presence of myositis and severe muscular weakness in KD is distinctly unusual and may lead to delays in diagnosis and administration of definite therapy. We report a 10-year-old boy who presented with fever, rash and proximal muscle and pharyngeal weakness. A clinical possibility of toxic shock syndrome or juvenile dermatomyositis was initially considered. However, he continued to have fever and developed periungual peeling of skin in fingers. Hence, a possibility of KD with myositis was considered. He showed prompt response to intravenous immunoglobulin and methylprednisolone. We also provide a review of similarly reported cases of KD myositis. It is important for clinicians to be aware of this atypical clinical presentation to avoid delays in diagnosis and treatment of KD.

Inborn errors of immunity (IEIs) are a group of heterogeneous disorders characterized by a broad clinical spectrum of recurrent infections and immune dysregulation including autoimmunity and lymphoproliferation (LP). LP in the context of IEI may be the presenting feature of underlying immune disorder or may develop during the disease course. However, the correct diagnosis of LP in IEI as benign or malignant often poses a diagnostic dilemma due to the non-specific clinical features and overlapping morphological and immunophenotypic features which make it difficult to treat. There are morphological clues to LP associated with certain IEIs. A combination of ancillary techniques including EBV-associated markers, flow cytometry, and molecular assays may prove useful in establishing a correct diagnosis in an appropriate clinical setting. The present review attempts to provide comprehensive insight into benign and malignant LP, especially the pathogenesis, histological clues, diagnostic strategies, and treatment options in patients with IEIs.

Chronic granulomatous disease (CGD) is an inherited defect of phagocyte function due to defective NADPH oxidase. Patients with CGD are not able to effectively clear the infections because of the defect in the phagocyte production of oxygen free radicals and are prone to recurrent bacterial and fungal infections. Inflammatory complications are also noted in CGD such as colitis, non-infective granulomas causing gastrointestinal or urinary tract obstruction, hemophagocytic lymphohistiocytosis, and arthritis. Studies on toll-like receptor pathways and neutrophil extracellular traps in CGD have shed light on the role of NADPH oxidase in the innate immunity and pathogenesis of infections in CGD. Some reports also indicate a reduction of memory B cells and defective production of functional antibodies in CGD. Though the exact mechanisms for non-infective inflammatory complications in CGD are not yet clear, studies on efferocytosis and defective autophagy with inflammasome activation have made a substantial contribution to our understanding of the pathogenesis of inflammation in CGD. We also discuss the clinical and molecular features of p40phox defects and a newer genetic defect, EROS. Clinical phenotypes of X-linked carriers of CYBB are also discussed. Keywords: Chronic granulomatous disease, Colitis, EROS, Genetics, Infections, Inflammation, p40phox

Primary immunodeficiency diseases (PIDs) refer to a heterogenous group of disorders characterized clinically by increased susceptibility to infections, autoimmunity and increased risk of malignancies.These group of disorders present with clinical manifestations similar to PIDs with known genetic defects but have either no genetic defect or have a somatic mutation and thus have been labelled as “Phenocopies of PIDs”. These diseases have been further subdivided into those associated with somatic mutations and those associated with presence of auto-antibodies against various cytokines.In this review, we provide an update on clinical manifestations, diagnosis and management of these diseases. Keywords: Anti-cytokine antibodies, Phenocopies, Primary immunodeficiency diseases, Somatic mutations

Background: Systemic autoinflammatory diseases (SAID) are rare inherited disorders involving genes regulating innate immune signaling and are characterized by periodic or chronic multi-systemic inflammation.Objective: To describe spectrum of clinical, immunological, molecular features, and outcomes of patients with SAID in India.Methods: Request to share data was sent to multiple centers in India that are involved in care and management of patients with Inborn Errors of Immunity. Six centers provided requisite data that were compiled and analyzed.Results: Data on 107 patients with SAID were collated—of these, 29 patients were excluded due to unavailability of complete information. Twelve patients (15%) had type 1 interferonopathies, 21 (26%) had diseases affecting inflammasomes, 30 patients (41%) had non-inflammasome related conditions and 1five patients (19%) had Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA). Type1 interferonopathies identified in the cohort included patients with Deficiency of Adenosine Deaminase 2 (DADA2) (six patients; five families); STING-associated vasculopathy infantile-onset (SAVI) (three patients, one family); Spondyloenchondro-dysplasia with Immune Dysregulation (SPENCD) (two patients). Diseases affecting inflammasomes include Mevalonate Kinase Deficiency (eight patients); Cryopyrin-Associated Periodic Syndromes (CAPS) (seven patients); NLR Family, Pyrin domain-containing 12 (NLRP12) (two patients); Familial Mediterranean fever (FMF) (two patients); Autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) (two patients). TNF receptor-associated periodic syndrome (TRAPS) (three patients); A20 haploinsufficiency (four patients); Deficiency of Interleukin 1 Receptor Antagonist (DIRA) (two patients) were categorized as non-inflammasome related conditions. There were significant delays in diagnosis Corticosteroids and other immunosuppressive agents were used for treatment as anti-IL-1 drugs and other biological agents were and still are not available in India. Eight (16.3%) patients had so far succumbed to their illness.Conclusions: This is the first nationwide cohort of patients with SAID from India. Clinical manifestations were diverse. Overlapping of clinical features with other relatively common rheumatological disorders often resulted in delays in diagnosis. More nationwide efforts are needed to enhance awareness of SAID among health care professionals and there is an urgent need to make targeted immunotherapies universally available.

Background Hereditary angioedema (HAE) is a rare inherited disorder characterized by sudden and unpredictable appearance of swelling. Surgical procedures, even minor ones, are known to precipitate an attack in these patients. C1 esterase inhibitor (C1-INH) therapy may be effective for short term prophylaxis in such situations. However, there is limited experience with short term prophylaxis in countries where C1-INH therapy is not available. Methods To report our experience of using short term prophylaxis for a dental procedure, a Cesarean section and a major hip surgery in one patient each with HAE in resource constrained settings. Results All 3 patients were given FFP before and during the procedure. While the first (a 6-year-old girl) and third patient (a 60-year-old male) were already taking stanozolol and the dose was doubled 5 days before the surgery, the second patient (28-year-old woman) was not taking any prophylaxis and she was initiated on stanozolol on the day of Cesarean section. The first patient was also given additional FFP one day after the dental procedure. After the procedure, the dose of stanozolol was decreased to baseline in patient 1 and 3 while it was discontinued in patient 3. All 3 patients tolerated the procedures well and had no related episodes of angioedema. Conclusions Dental and other major surgical procedures in patients with HAE are known to precipitate an episode of angioedema. In countries where C1-INH therapy is not available, attenuated androgens and FFP may be used to prevent these episodes.

Self-healing juvenile cutaneous mucinosis (SHJCM) is a rare childhood disease with characteristic cutaneous and rheumatic manifestations. Cutaneous manifestations include a combination of nodules affecting peri-articular (especially interphalangeal joints) and head and neck areas; and linearly arranged ivory white papules over an erythematous indurated skin. Despite a benign course, an abrupt onset of symptoms with extensive cutaneous involvement often leads to parental anxiety, overenthusiastic evaluation and sometimes aggressive treatment. A peculiar cutaneous distribution in SHJCM including nodular lesions and periorbital edema, arthritis and arthralgia in a few cases, may simulate juvenile dermatomyositis. It is, therefore, important for dermatologists and pediatricians to be aware of this entity. In this report, we describe two cases of SHJCM and briefly review similarly reported cases in children.

Autoinflammatory diseases (AIDs) are a heterogeneous group of genetically inherited disorders involving genes regulating innate immune response. The genetic basis of several AIDs has been characterized and many new syndromes have been identified in the past few years. This review focuses on some of the common AIDs encountered in clinical practice.

Kawasaki disease (KD) is a common acute systemic vasculitis of childhood. Although transaminitis and hydrops of the gallbladder are well-recognized features of KD, features of hepatic failure are u...

Juvenile idiopathic arthritis (JIA) refers to a group of disorders characterised by wide phenotypic diversity and genetic heterogeneity. Disordered immune response to an environmental trigger in a genetically predisposed individual is the proposed mechanism for most JIA subtypes.1 2 There are emerging reports on new gene locus being identified especially in families with many affected members.3 4 We report three sisters with polyarthritis who were identified to have causative variant in Laccase domain containing one ( LACC1 ) gene by whole exome sequencing. A non-consanguineous family from north-western part of India reported with three daughters (P1, P2 and P3) having polyarticular joint disease. The onset of symptoms in the third child (11 months) prompted the parents to seek medical help. The eldest sister was 5 years and 9 months old, while the second daughter was 3 years old at the time of presentation. The chronology of symptoms was similar in all three children. Joint symptoms started in infancy at around 9–10 months of age with involvement of knee and ankle and rapidly progressed to involve small joints and cervical spine too (figure 1A–C). Over the next 2 years, multiple joint involvement, pain, deformities and contractures …