An Autopsy Case of Wiskott-Aldrich Syndrome Revealing "FDC-Only Lymphoid Follicles" in Lymphoid Tissue: A Morphologic Correlate of Defective Immune Synapse.

Wiskott-Aldrich Syndrome (WAS) is an inherited disorder characterized by the classical triad of eczema, micro-thrombocytopenia, and immune deficiency. This disease affects the hematopoietic cells to a variable extent. The spectrum of clinical and laboratory data for WAS has been well described in the literature though there is a paucity of its histopathologic and immunohistochemical correlates. The current case describes the autopsy findings of this rare entity in an 8-year old male child with specific recognition of altered histology noticed in the lymphoreticular tissues. The predominant morphological finding in lymphoid tissue was atretic hyalinized germinal centers labeled as "the follicular dendritic cell (FDC)-only lymphoid follicles." Immunohistochemistry revealed a reduction in germinal-center B-cells, T-follicular helper cells, attenuated mantle zone, FDC proliferation, and paracortical plasmacytosis. This case highlights the crippled immune cell population in WAS, ultimately leading to the morphology of atretic follicles rich in FDCs.

Kawasaki disease malingering as juvenile dermatomyositis: case-based review : Myositis in Kawasaki disease.

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.

Self-healing juvenile cutaneous mucinosis, a sclerodermoid disorder simulating juvenile dermatomyositis: a case-based review.

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.

Granulomatous inflammation and hypogammaglobulinemia: Clinical conundrum of familial hemophagocytic lymphohistiocytosis type 5.

Familial hemophagocytic lymphohistiocytosis (HLH) is an inherited disorder characterized by systemic hyperinflammation caused by an uncontrolled immune response mediated by T-lymphocytes, natural killer (NK) cells, and macrophages. Most children with familial HLH present within first 2 years of life and can have fatal disease unless hematopoietic stem cell transplant (HSCT) is performed (1). However, few patients may have late presentation and prolonged survival. With increasing awareness and facilities to identify HLH these disorders are being identified beyond infancy (2-4). Clinical and laboratory features are often similar to other primary immune deficiency diseases and pose diagnostic challenges (4-6). We report two patients who presented beyond the first decade of life with HLH, granulomatous inflammation, hypogammaglobulinemia, reduced B cells and were diagnosed to have familial HLH type 5 due to defect in STXBP2 gene.

SELF-INFLICTED LASER-INDUCED MACULOPATHY MASQUERADING AS POSTERIOR UVEITIS IN A PATIENT WITH SUSPECTED IgG4-RELATED DISEASE.

PURPOSE: To report the clinical presentation and imaging features in a case of bilateral self-inflicted handheld laser-induced maculopathy which masqueraded as progressive posterior uveitis in a patient with suspected IgG4-related disease. METHODS: Case report with clinical history, fundus photographs, fluorescein angiography, indocyanine green angiography, and swept-source optical coherence tomography. RESULTS: A young Asian Indian man presented with sudden progressive bilateral visual loss over the past 1 week. He was being treated with oral corticosteroids for multiple subcutaneous skin lesions believed to be due to IgG4-related disease. Findings included bilateral central areas of outer retinal disruption with eccentric linear and serpentine lesions showing hypoautofluorescence. Hyperreflective bands extending from the retinal pigment epithelium and interdigitation zone to the outer plexiform layer were present on swept-source optical coherence tomography. After careful history and evaluation of multimodal imaging, posterior uveitis was excluded, and a diagnosis of handheld laser-induced maculopathy was established. CONCLUSION: Pattern recognition is important in establishing a diagnosis of self-inflicted handheld laser-induced maculopathy which can masquerade as posterior uveitis. Increasing availability of powerful Class IIIb laser devices in both developed and developing countries will likely increase the incidence of this entity.

Psychosocial impact of SARS- CoV-2 outbreak on patients with pediatric-onset systemic lupus erythematosus and their caregivers.

Aim: To assess distress, insomnia, and psychosocial impact of SARS-CoV-2 outbreak on children with SLE and their caregivers. Methods: Patients with pSLE undergoing treatment in the Department of Pediatrics, PGIMER, Chandigarh, and their caregivers were enrolled. Questionnaires were sent to eligible patients and their parents through email or WhatsApp and telephonic interviews were conducted. Self-designed SLE-COVID-19 stress questionnaire; Peritraumatic Distress Inventory; Insomnia Severity Index, Positive and Negative Affect Schedule were used. Ethical approval was sought from Institutes Ethics Committee (IEC/2020/000583). Results: Telephonic connection was possible with 80 families (160 participants). Telephonic contact was possible with 80 families (160 participants); off these 61 children with pSLE (78.2%) and 55 caregivers (70.5%) responded to the questionnaire. Among participants, 23% patients, and 21.8% caregivers were severely stressed about SARS-CoV-2 infection; 78.7% patients and 80% caregivers had heard about hydroxychloroquine (HCQ) being used for the treatment of COVID-19; 52.7% caregivers exhibited moderate concern about shortage of HCQ; and 52.5% patients, and 43.6% caregivers were worried about side effects of HCQ. We found that 20 (32.8%) patients and 18 (32.7%) caregivers experienced significant distress. Majority of participants reported sleep disturbances. High positive affect scores were seen in 40 (65.5%) patients and 43 (78.2%) caregivers, low positive affect scores were noted in 21 (34.5%) patients and 12 (21.8%) caregivers. Conclusion: Patients with pSLE and their caregivers are at risk of psychosocial problems during the COVID-19 pandemic. Psychological interventions can be very helpful.

Lymphoproliferation in Inborn Errors of Immunity: The Eye Does Not See What the Mind Does Not Know.

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.

Features of Hemophagocytic Lymphohistiocytosis in Infants With Severe Combined Immunodeficiency: Our Experience From Chandigarh, North India.

Background: Hemophagocytic lymphohistiocytosis (HLH) is characterized by uncontrolled and excessive inflammation leading to high mortality. Aetiology of HLH can be primarily due to genetic causes or secondarily due to infections or rheumatological illness. However, rarely T-cell deficiencies like severe combined immunodeficiency (SCID) can develop HLH. Objective: To describe clinical and laboratory features of SCID cases who developed HLH. Methods: We collected clinical, laboratory, and molecular details of patients with SCID who developed HLH at our center at Chandigarh, North India. Results: Of the 94 cases with SCID, 6 were noted to have developed HLH-like manifestations. Male-female ratio was 5:1. Median (inter-quartile range) age of onset of clinical symptoms was 4.25 months (2-5 months). Median (inter-quartile range) delay in diagnosis was 1 month (1-3.5 months). Family history of deaths was seen in 4 cases. Molecular defects in IL2RG were seen in 5 out of 6 cases. Documented infections include disseminated bacillus calmette-guerin (BCG) infection (n=2), blood stream infections (n=3) with Staphylococcal aureus (n=1), Klebsiella pneumonia (n=1), and Pseudomonas aeruginosa (n=1), pneumonia (influenza H1N1 strain, and K. pneumoniae (n=1). Conclusion: Children with SCID can present with HLH-like manifestations secondary to fulminant infections. A high index of suspicion of SCID is needed in infants who present with HLH who have an associated infection or a suggestive family history. Occurrence of HLH-like manifestations in SCID suggests that T-lymphocytes may not have a significant role in immunopathogenesis of HLH.

Spectrum of Systemic Auto-Inflammatory Diseases in India: A Multi-Centric Experience.

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.