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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 (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.

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

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.

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 …

Background Pancreatitis is a rare but potentially life-threatening complication of systemic lupus erythematosus(SLE).SLE-related pancreatitis can be a presenting manifestation of SLE or may occur during follow-up. Methods We have reviewed the clinical records of 140 children with SLE between period of 1993–2018.We report 3 children with SLE who presented with acute pancreatitis. Results Case1–12-year-girl presented with fever and alopecia.Examination revealed pedal oedema,periorbital puffiness,large joint arthritis.Investigations showed anemia,thrombocytopenia,elevated erythrocyte sedimentation rate(ESR),normal renal functions,microscopic hematuria,nephrotic range proteinuria,hypocomplementemia,antinuclear antibody (ANA) 4+,elevated anti double stranded DNA (anti-ds DNA),negative antiphospholipid antibodies (APLA) titre(table).Renal biopsy revealed Class 3 lupus nephritis and initiated on intravenous methylprednisolone.Two days later,she developed severe epigastric pain and vomiting.The pain increased in severity and physical examination revealed marked tenderness in the epigastrium.Serum amylase and lipase were elevated.Clinical possibilities included steroid induced pancreatitis and lupus pancreatitis.In view of severity of symptoms,intravenous methylprednisolone was continued following which she showed a dramatic improvement and normalisation of pancreatic enzymes.There has been no recurrence of pancreatitis over 3 years of follow-up period and remained well on low dose oral prednisolone(5 mg),mycophenolate-mofetil and hydroxychloroquine. Case2-A-6-year-old presented with pain abdomen and vomiting.Physical examination showed epigastric tenderness.Investigations showed anemia,thrombocytopenia,elevated amylase levels(table).Computerised tomography(CT) abdomen revealed acute necrotising pancreatitis.A follow-up ultrasound abdomen revealed a pancreatic pseudocyst.He had a second episode of acute pancreatitis along with anasarca after 3 months which improved with conservative management.Investigation showed anemia,nephrotic range proteinuria and microscopic haematuria(table).ANA was positive with normal complement levels and negative anti-dsDNA titres(table).Lupus band test on skin biopsy was positive.Renal biopsy showed mesangioproliferative-glomerulonephritis with full house pattern.Following the initiation of steroids,he improved and there has been no recurrence of pancreatitis over the next 4 years. Case 3–9 year-girl presented with generalised rash,alopecia for 5 months.She also had pain abdomen for last 2 months.Investigations showed elevated amylase,ultrasound abdomen revealed acute pancreatitis.She had undergone a laparotomy elsewhere.Examination showed generalised pigmented rash,alopecia, periorbital puffiness,hard palatal ulcer,surgical scar on the abdomen.Investigations showed anemia, normal platelet count,elevated ESR,normal renal functions,nephrotic range proteinuria,elevated serum amylase.Ultrasound and CT abdomen revealed a pancreatic pseudocyst.A clinical possibility of SLE with acute pancreatitis and lupus nephritis was considered.Further investigations were suggestive of lupus(table).Workup for APLA revealed positive lupus anticoagulant.Her skin biopsy was consistent with lupus and renal biopsy revealed class 4 lupus nephritis.She was initiated on oral prednisolone and was given pulses of intravenous cyclophosphamide.There has been no recurrence of pancreatitis over 12 years follow-up. Conclusions Pancreatitis can at times,be the presentation of childhood lupus and requires prompt and aggressive management. Funding Source(s): None

Background Macrophage activation syndrome (MAS) can, at times, be the presentation of pediatric lupus and diagnosis requires high index of suspicion. Methods We retrospectively studied 140 pediatric lupus patients from January 1993- November 2018 and collected clinical and laboratory data of patients (3) who had MAS as presenting manifestation. Results Case 1 was 11-year-old girl with fever for 4 months associated with rash and generalized body swelling for 1 month. Examination revealed rash over malar area and ear lobules, anasarca, hepatomegaly, bilateral pleural and pericardial effusion. In view of multisystem involvement a possibility of lupus was considered which was confirmed by investigations (table 1). She had elevated ferritin and fasting triglyceride and low fibrinogen. A clinical possibility of lupus with associated MAS was considered. She received pulses of methylprednisolone, one dose of intravenous immunoglobulin following which she improved. In view of nephrotic range proteinuria she was started on induction regimen with cyclophosphamide and shifted to mycophenolate in maintenance. Her initial SLEDAI-2k was 32- this decreased to 4 at 3 year follow-up. Case 2 was a 9-year-old girl with fever, rash, generalized body swelling for 1 month and altered sensorium for 4 days. Examination revealed pallor, oral ulcers and hepatomegaly. She was in shock at presentation. In view of multisystem involvement a possibility of lupus was considered which was confirmed by investigations (table 1). She had pericardial effusion and low ejection fraction (25%). A possibility of MAS was considered and investigations revealed hyperferritinemia, elevated triglyceride and hypofibrinoginemia. She was given methylprednisolone pulses and continued on oral prednisolone, mycophenolate and hydroxychloroquine. Her initial SLEDAI-2k was 17- this decreased to 0 at 3 year follow-up. Case 3 was an 8-year-old girl who had fever, rash and body swelling for 15 days. She had tachycardia, tachypnea, pallor, anasarca, subconjunctival bleed and frontal alopecia. She had pleural and pericardial effusion. In view of multisystem involvement a possibility of lupus was considered which was confirmed by investigations (table1). She had high ferritin and triglyceride. So a possibility of MAS was considered and she received pulse methyl prednisolone and intravenous immunoglobulin. She also had hematuria and proteinuria (renal biopsy could not be performed as she was sick and had thrombocytopenia) so was given pulse cyclophosphamide followed by mycophenolate. Her initial SLEDAI-2k was 25- this decreased to 0 at 2 year follow-up. Conclusions MAS can be the presenting manifestation of pediatric lupus and may contribute to disease severity and requires aggressive management Funding Source(s): None

Background Pleuritis and pericarditis,with or without effusion,are the commonest pulmonary and cardiovascular manifestations in children with systemic lupus erythematosus(SLE).However,SLE presenting as an isolated pericardial effusion with cardiac tamponade is distinctly unusual. Methods We report one such case who went on to develop recurrent episodes of pericardial effusion and tamponade. Results A-14-year-old girl presented with high grade fever,progressive dyspnea,pedal edema,periorbital puffiness for 7 days.She also had history of malar rash and photosensitivity.There was no history of oral ulcer and hair loss.Physical examination showed a prominent malar rash;heart rate 140/min;respiratory-rate 40/min;muffled heart sounds;hepatomegaly and ascites.She was initiated on decongestive measures with furosemide and digoxin.Chest X-ray showed cardiomegaly(cardiothoracic ratio 68%);2D-echocardiography(2D-ECHO) revealed cardiomegaly,pericardial effusion and features consistent with cardiac tamponade.She underwent emergency pericardiocentesis,400 ml of serosanguineous fluid was drained followed by prompt clinical improvement.Investigations showed hemoglobin 90 g/L; total leukocyte count 1.3 × 106/L and lymphocyte count 0.18 × 106/L;platelets of 356 × 109/L.Urinalysis and renal function tests were unremarkable.Tuberculin skin test was non-reactive.Thyroid function tests were normal.In view of febrile illness, malar rash,photosensitivity, pericardial effusion,cardiac tamponade and lymphopenia,SLE was considered.Work-up showed positive antinuclear antibody (ANA)4+diffuse ANA positivity;positive anti-double stranded DNA(anti-dsDNA)−60(normal:4.2 IU/ml);C3 51.8 mg% (normal 50–150 mg%).Skin biopsy revealed IgG and C3 deposits.Pericardial fluid analysis revealed low complement(C3 Conclusions Pericardial effusion with cardiac tamponade at presentation of childhood lupus is distinctly unusual and so is the rarity of recurrent pericardial effusion with cardiac tamponade.Our patient continued to have recurrences on follow-up that responded to glucocorticoids. Funding Source(s): None

Background Though abnormal liver tests can be seen during the course of disease in lupus, liver involvement as a presenting manifestation is uncommon in children with lupus. Methods We retrospectively studied 140 pediatric lupus patients from January 1993- November 2018 and collected clinical and laboratory data of patients (3) who had liver involvement as presenting manifestation. Results Case 1 was 13-year-old girl with fever and joint pain for 7 months associated with rash and yellow discoloration of eyes and body for 1 month. She also had altered behavior for 3 days. Examination revealed malar rash, pallor, jaundice, bilateral knee arthritis and hepatosplenomegaly. Investigations revealed (table 1) anemia, thrombocytopenia and lymphopenia. She had conjugated hyperbilirubinemia. Transaminases were elevated. Further investigations confirmed diagnosis of lupus (table 1). Markers for autoimmune hepatitis (SMA; LKM) were negative. She received pulse methylprednisolone followed by tapering doses of oral prednisolone. In view of neurological involvement she also received cyclophosphamide and shifted to azathioprine later. Her initial SLEDAI-2k was 22, that decreased to 4 at 2 year follow-up. Case 2 was a 11-year-old boy with fever, rash and joint pain for 1 month. Examination revealed pallor, malar rash, oral ulcers, arthritis of bilateral elbow and knee and hepatomegaly. Investigations (table 1) revealed anemia; thrombocytopenia; leucopenia and lymphopenia. In view of multisystem involvement a possibility of lupus was considered which was confirmed by investigations (table 1). He had elevated transaminases. There was no coagulopathy. He was started on oral prednisolone. She also had class 3 lupus nephritis and received pulse cyclophosphamide followed by azathioprine in maintenance. Her transaminases decreased in follow-up. Her initial SLEDAI-2k was 18, that decreased to 2 at 2 year follow-up. Case 3 was an 9-year-old girl who had rash and abdominal distention for 20 days and fever and altered sensorium for 6 days. On examination she had pallor, malar rash, ascitis and hepatosplenomegaly. Investigations revealed anemia; thrombocytopenia; leucopenia and lymphopenia. She had conjugated hyperbilirubinemia, elevated transaminases and coagulopathy. She also had deranged renal function tests. Ultrasonography reveals coarse echotexture, gross ascitis and splenomegaly. Possibility of lupus with acute on chronic liver decompensation was considered which was confirmed by investigations (table 1). She was given methyl prednisolone. She had progressive azotemia so possibility of rapidly progressive renal failure was considered and cyclophosphamide was given. However, she developed refractory shock and eventually expired. Conclusions Hepatic involvement at presentation in lupus can be multifaceted and poses challenge in diagnosis. Funding Source(s): None