Mendelian susceptibility to mycobacterial disease (MSMD), caused by IL12RB1 or IL12B mutations, typically presents with intra-cellular infections such as BCG-adenitis or Salmonella. Rarely, patients with IL12RB1/IL12B defects can exhibit cutaneous manifestations such as Henoch-Schonlein purpura (HSP). This study aimed to evaluate such vasculitic manifestations in genetically confirmed cases with MSMD in India and review the literature for similar associations. We included nine patients with genetically proven MSMD presenting with features of HSP-like small vessel vasculitis from pediatric immunology clinics across three tertiary care centers in India. Clinical, laboratory, histopathological, and genetic data were recorded using a structured proforma. Skin biopsy findings, IgA levels, renal involvement, and infection history were analyzed. Additionally, a literature review was performed using PubMed, Scopus, and Google Scholar databases to identify similar reported cases. In our cohort, eight patients had IL12RB1 defect, and one had IL12B defect. All had maculopapular purpuric rash in lower limbs, predominantly in the anterior aspect of legs and posterior thighs resembling the rash of HSP. Leukocytoclastic vasculitis was observed in 77.7% patients (n = 7), with two out of five had IgA deposits in dermo-epidermal junction. Concurrent infections due to Salmonella sp. and Pandorea apista were documented in 44.4% (n = 4) and 22.2% (n = 2), respectively. Treatment focused on antimicrobial therapy led to clinical improvement. The HSP-like vasculitic rash usually occurred in setting of underlying bacterial infections in patients with particularly IL12RB1/IL12B defects. These skin lesions can also be considered as one of the potential clinical clues for underlying IL12RB/IL12B defects.

BACKGROUND:Pemphigus foliaceus (PF) is an uncommon autoimmune disease characterized by superficial blistering and erosions of the skin. The literature on PF globally is limited. Understanding clinicodemographic heterogeneity in PF is crucial for improving outcomes for affected individuals. OBJECTIVES:To study the clinicodemographic characteristics and treatment outcomes of patients with PF in north India. METHODS:A retrospective study was conducted of patients with PF registered at the authors' clinic at the Postgraduate Institute of Medical Education and Research in Chandigarh, north India, between November 2013 and June 2023. RESULTS:In total, 103 patients with PF were included in the study. The mean (SD) age at disease onset was 40.4 (15.7) years, with a male-to-female ratio of 1.7 : 1. The median duration of disease at presentation was 18 months (range 1-240). The most commonly prescribed treatment was topical corticosteroids (n = 98/103; 95.1%) or oral corticosteroids (n = 97/103; 94.2%), either alone or in combination with steroid-sparing adjuvants. Rituximab was the commonest adjuvant and was used in 43.7% (n = 45/103) of patients. Overall, 75.7% (n = 78/103) of patients achieved clinical remission on minimal treatment (CRmin) in a mean of 6.5 (3.9) months. Clinical remission off treatment (CRoff) was achieved in 10.4 (6.0) months in 67.0% (n = 69/103) of patients. Among patients in the rituximab group, CRmin was achieved in 91.1% (n = 41/45) of patients in 6.3 (4.6) months and CRoff was achieved in 82.2% (n = 37/45) of patients in 9.0 (5.6) months. CONCLUSIONS:In the present study PF was more common in men aged between 40 and 60 years. Corticosteroids (topical/systemic) formed the mainstay of treatment, with rituximab being the most commonly used steroid-sparing adjuvant. Prospective studies in a larger cohort are required for a better understanding of this disease in nonendemic locations.

Abstract Purpose Melorheostosis, or Leri’s disease, is a rare sclerotic bone disorder characterized by a wax-like appearance due to excess cortical bone formation. It affects both genders equally, with a prevalence of approximately 0.9 cases per million, and typically presents during adolescence. Patients commonly experience pain and functional disability, with the potential for contractures and deformities in chronic cases. Method This retrospective review was based on the institute’s rare metabolic bone disease registry ( www.rarembd.in ). It evaluated the clinical profile, biochemistry, and radiology of patients presented to the institute and incorporated into the registry. This study incorporated subjects presented to this institute between January 2007 and October 2024. Results Among 268 rare metabolic bone disease patients incorporated into the registry, 3 were diagnosed with melorheostosis. All three were female, and their ages at presentation were 25, 27, and 45 years. Presenting symptoms included localized pain and functional impairment. Each case demonstrated distinct radiological variants: one showed the classic candle wax appearance, while others exhibited myositis ossificans-like and endosteal osteoma-like features. Management focused on symptomatic relief with non-steroidal anti-inflammatory drugs and bisphosphonates, with variable responses. Conclusion In our small series, all three patients were female with lower limb involvement, presenting with pain and functional impairment. Each case demonstrated a distinct radiological variant of melorheostosis. Management was symptomatic with variable response. The rarity of melorheostosis underscores the importance of awareness and thorough differential diagnosis in clinical practice.

Eccrine poroma (EP) is a benign adnexal tumor that typically presents as a solitary, slow-growing lesion on acral sites, but recurrence and immunosuppression may increase the risk of malignant transformation. We report a recurrent EP in a 28-year-old man with chronic myeloid leukemia post-stem cell transplant on long-term immunosuppression. The patient presented with a moist, sessile, exophytic nodule on the thigh that had recurred six months after simple excision. Dermoscopy showed polymorphic vessels with interlacing white cords. Owing to recurrence and concern for porocarcinoma, Mohs micrographic surgery (MMS) was performed. Stage 1 margins revealed positivity between 3 and 6 o’clock, necessitating a second stage, after which margins were clear. Reconstruction was achieved with a keystone advancement flap. Histopathology confirmed benign EP. At 15-month follow-up, no recurrence was noted. This case highlights MMS as an effective tissue-sparing therapeutic option for recurrent EP in immunocompromised patients.

Introduction: Homozygous mutations in the AGTPBP1 gene are associated with childhood-onset neurodegeneration and cerebellar atrophy (CONDCA). These mutations disrupt neuronal maintenance, leading to progressive motor and cognitive deficits. This case highlights the pathological findings and systemic complications in a 4.5-month-old boy with this rare genetic disorder. Case Report: A 4.5-month-old boy presented with global developmental delay and progressively worsening floppiness of the body for the past 2 months. There was a history of similar illness in his previous sibling, who died at 2.5 months of age. The serum creatine kinase of the index child was mildly elevated. Antemortem muscle biopsy had revealed the presence of neurogenic atrophy. Peripheral blood count revealed persistent lymphopenia (ALC range: 1,270/μL to 2,482/μL). The child developed severe respiratory distress and succumbed to his illness at 5 months of age. The autopsy revealed the atrophy of cerebellar folia with a striking reduction of Purkinje and granular cells and preserved molecular layer. There was thinning of the corpus callosum and anterior horn cell degeneration in the spinal cord. Lung examination demonstrated fibrinous bronchitis, bronchiolitis, and pneumonia; a result of adenovirus infection confirmed by electron microscopy and PCR. The thymus was absent. Genetic testing identified a homozygous mutation in the AGTPBP1 gene (c2833C>T), confirming the diagnosis of CONDCA. Conclusion: This is the first autopsy description of CONDCA with detailed neuropathological evaluation. Although cerebellar atrophy is well known, this case reveals a wider neuropathological change and thymic aplasia in such patients. This case highlights the structural consequences of the AGTPBP1 gene-associated enzyme deficiency crucial for post-translational modifications of tubulin, resulting in the degeneration of specific sets of neurons and immune deficiency secondary thymic involvement.

BACKGROUND:The desmoglein compensation hypothesis (DCH) proposes that clinical and histopathological features of pemphigus correlate with differential expression of desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3) in skin and mucosa, and corresponding autoantibody profiles. While DCH explains many classical patterns, increasing exceptions have challenged its universality. AIM:This study aimed to correlate clinical phenotype and histopathological split level with anti-Dsg1 and anti-Dsg3 antibody profiles in pemphigus vulgaris (PV) and pemphigus foliaceus (PF), and evaluate consistency with DCH. METHODS:In this bicentric retrospective study, 106 patients with confirmed pemphigus (93 PV, 13 PF) were included. Clinical classification was based on presentation (cutaneous, mucosal, mucocutaneous). Histopathology was reviewed for split level (subcorneal, suprabasal, dual), and serum Dsg1/Dsg3 IgG levels were recorded. Concordance with DCH was assessed. RESULTS:In PF, splits were subcorneal in 6 (46.2%), suprabasal in 3 (23.1%), and both in 4 (30.7%). Eight (61.5%) had isolated anti-Dsg1 IgG, consistent with DCH. In PV, 75 (80.6%) had suprabasal splits, 7 (7.5%) dual splits, and 4 (4.3%) subcorneal splits. Among 16 mucosal PV cases, only 6 (37.5%) had isolated anti-Dsg3 IgG. Highest fidelity to DCH was seen in mucocutaneous PV (56/75; 74.7%) with dual anti-Dsg1 and Dsg3 positivity. Two patients with cutaneous-only PV showed dual positivity with suprabasal splits. CONCLUSION:While DCH explains many classic presentations, nearly one-third of patients in our cohort exhibited discordant clinical, serologic, or histologic features. These findings highlight the need for more comprehensive models of pemphigus pathogenesis that incorporate antibody titers, affinity, subclass, and non-desmoglein targets.

BACKGROUND:Meningiomas are the most common dural-based intracranial tumors, yet Indian literature is predominantly composed of limited single-center studies, restricting nationwide representation and data-driven decision making. With artificial intelligence (AI) becoming increasingly relevant in neuro-oncology for diagnosis, segmentation, and outcome prediction, the lack of a large, standardized national dataset poses a major barrier. The Medical Imaging Datasets for India (MIDAS) initiative, a collaborative national effort involving ICMR, IISc, and ARTPARK, aims to create high-quality, annotated medical imaging repositories that can support clinical research and AI model development. As a part of this initiative, we developed a multicenter national repository of dural-based lesions. METHODS:This ambispective study included patients with radiologically suspected and histopathologically confirmed dural-based lesions from seven neurosurgical centers across India (January 2022-July 2025). Standardized de-identified demographic, clinical, imaging, and pathological data were collected. Imaging was archived in DICOM format and annotated using ITK-SNAP, while histopathology followed WHO-2021 CNS tumor guidelines. Statistical analysis was performed using descriptive and comparative measures. RESULTS:Among 586 patients, women constituted two-thirds of the cohort, with a mean age of 47.2 years. Meningiomas accounted for 98.3 % of cases and were predominantly WHO Grade I, most commonly of transitional and meningothelial subtypes. Convexity, parasagittal, and falcine locations were most frequently involved. A small but important proportion of lesions were non-meningiomatous, including schwannomas, solitary fibrous tumors, granulomatous, and metastatic lesions. Simpson Grade II resection was the most common surgical outcome, and a subset of patients underwent postoperative adjuvant radiosurgery. CONCLUSION:This MIDAS-linked national repository represents the largest structured dataset of dural-based lesions from India, integrating standardized clinical, imaging, and pathological information across multiple centers. In addition to defining national disease patterns, the availability of curated imaging and volumetric segmentations provides a strong translational platform for future artificial intelligence-based research, including automated segmentation, diagnostic classification, and outcome prediction.

Background:Central nervous system (CNS) invasive mould infection (IMI) is a rare but life-threatening condition. Limited large-scale studies hinder the understanding of its clinical characteristics and optimal management strategies. Methods:This was a cohort study. We reviewed confirmed patients of CNS IMI (January 2004-March 2025) by microbiological (direct microscopy and/or culture) and/or histopathological evidence at our tertiary care hospital. Clinical, demographic and mycological characteristics were analysed and compared. Findings:Among 1321 brain abscess/biopsy samples, 127 patients (9.6%) were of fungal origin (adults, 100; paediatrics, 27). The median age was 30 (IQR: 27) years, with male predominance (71.7%). Adults were significantly infected by melanized fungi (p = 0.003). Seventy-four percent of patients had no identifiable underlying immunocompromising condition. The median duration of symptoms was 15 days (IQR: 23 days), including headache (61.4%) and seizures (50.4%). Frequency of fever was significantly higher in infection by melanized fungi (p = 0.02). Frontal lobe involvement was common in paediatric age (OR 0.379, 95% CI 0.141-1.019; p = 0.05). Aspergillus spp. (56.3%) and Cladophialophora bantiana (21.36%) were the predominant pathogens. Deniquelata barringtoniae was reported as a human pathogen. Voriconazole (61.4%) and liposomal amphotericin B (28.3%) were the primary antifungals used. Surgical intervention was performed in all patients. Partial excision (66.7% vs 38.0%, OR 0.306, 95% CI 0.125-0.751; p = 0.01) and use of liposomal amphotericin B (55.6% vs 21%, OR 0.213, 95% CI 0.087-0.522 p = 0.001) were common in paediatric patients. The overall mortality was 30.7%, complete excision was significantly more frequent among survivors than non-survivors (67.0% vs 30.8%; OR 0.218, 95% CI 0.097-0.492; p = 0.001). Lack of headache (p = 0.044) and partial excision surgery (p = 0.001) were independently associated with poor outcome. Interpretation:We describe a compendium of CNS IMI in patients from India, highlighting distinct clinical patterns and treatment outcomes across age groups and fungal types. This warrants investigation of host and pathogen-related factors in the country. Funding:Funding included Department of Science and Technology-Science and Engineering Research Board (DST-SERB), New Delhi, India and Indian Council of Medical Research (ICMR), New Delhi, India.

Summary:Medullary thyroid carcinoma (MTC) constitutes 5-10% of thyroid malignancies but accounts for 15% of thyroid cancer-related mortality. Twenty percent of MTC are hereditary and are part of familial MTC or multiple endocrine neoplasia (MEN) syndromes. Classical MTC presents as a nodular goiter with or without lymphadenopathy, or occasionally diarrhea and metastatic symptoms. Several patients in our cohort had unusual features that delayed diagnosis. The standard management remains surgical resection, with tyrosine kinase inhibitors (TKIs) in RET mutation-positive or RET mutation-negative metastatic cases and/or Lutathera peptide receptor radionuclide therapy (PRRT) used in disseminated disease, and external beam radiotherapy for locally aggressive or infiltrative retaining a limited role. However, some patients developed therapy-related complications or exhibited resistance to treatment. Of the 80 MTC patients reviewed, this case series highlights 10 atypical presentations in nine cases : 3 unusual tumors along with MTC, namely chondrosarcoma, carcinoma prostrate, and ectopic Cushing's syndrome; 4 unusual associations or presenting manifestations: pneumoconiosis masquerading as lung metastasis, Marfanoid habitus in MEN-2A and VHL spectrum disease, 1 with skull metastasis, and 2 cases with TKI-related complications in the form of glomerulonephritis and one patient displayed Marfanoid habitus with a RET mutation but without MEN2B or fibrillin gene mutation, while another developed bowel perforation secondary to lenvatinib therapy emphasizing diagnostic and therapeutic challenges and rare tumor associations. This series underscores the heterogeneity of MTC and the need for thorough evaluation and personalized management. Greater clinician awareness of MTC's diverse presentations is essential to improve early diagnosis and optimize treatment outcomes. Learning points:Diverse and atypical clinical presentations can obscure the diagnosis of MTC. Management of MTC remains complex due to therapy-related complications and resistance. Molecular diagnostics enable better risk stratification and personalized care.

BACKGROUND:Primary localized cutaneous amyloidosis (PLCA) is a rare chronic heterogeneous group of disorders with deposition of abnormally folded beta-pleated protein in the dermo-epidermal junction and dermis. There are three major forms of PLCA, including lichen amyloidosis, macular amyloidosis, nodular amyloidosis, and a rare variant, amyloidosis cutis dyschromica. We aimed to evaluate the role of immunohistochemistry (IHC) in the diagnosis of PLCA. PATIENTS AND METHODS:A retrospective 8-year audit (2017-2024) was performed. All cases of PLCA were subjected to a panel of IHC, including high molecular weight cytokeratin (HMWCK), Kappa and Lambda light chains; and serum amyloid A. The demographic details and clinical features, along with site predilection, were correlated with the pathological subtypes. RESULTS:We included 42 cases of PLCA, among which lichen amyloidosis was the most common subtype (50%), followed by macular amyloidosis, nodular amyloidosis, and amyloidosis cutis dyschromica, with a predilection for the upper back. IHC displayed HMWCK positivity in cases of lichen amyloidosis (14/21, 66.7%), macular amyloidosis (7/11, 63.6%), and amyloidosis cutis dyschromica (2/3, 66.7%). All cases of nodular amyloidosis showed light chain restriction using a combination of IHC and direct immunofluorescence. LIMITATIONS:Retrospective nature of the study, relatively small sample size, and not performing IHC for other small molecular weight keratins. CONCLUSION:The findings in our study confirm that the amyloid in macular amyloidosis, lichen amyloidosis, and amyloidosis cutis dyschromica is derived from epidermal keratinocytes. IHC for HMWCK should be part of diagnostic workup as it can detect very small amount of amyloid deposition, which may be overlooked during routine evaluation. Nodular amyloidosis demonstrates light chain restriction, indicating the need to exclude systemic amyloidosis.

Psoriasiform sarcoidosis is a rare variant of cutaneous sarcoidosis, characterized by erythematous, raised, scaly plaques that resemble psoriasis. The condition can be difficult to differentiate from other dermatological conditions (Yanardag H, Tetikkurt C, Bilir M et al. Clinical significance of psoriasiform sarcoidosis. Arch Clin Med Case Rep 2020; 4: 471–82). Herein, we report the case of a 38-year-old man who presented with a 7-month history of progressively worsening cutaneous lesions, along with a 5-year history of shortness of breath, currently classified as Modified Medical Research Council grade III. On examination, erythematous annular plaques with peripheral scaling and central clearing were noted on his face, and reddish-orange plaques with adherent whitish scales and superficial crusting were observed on the lower extremities. Dermoscopy revealed yellow-orange structureless areas, glomerular vessels and polarizing white lines, which are characteristic of sarcoidosis. A chest computed tomography (CT) scan showed cavitary lesions, lobular septal thickening and enlarged hilar lymph nodes, indicative of pulmonary involvement. Histopathological examination of a punch biopsy from the lower legs showed well-formed non-necrotizing granulomas, composed of epithelioid cells with multinucleated giant cells extending into the subcutis, confirming sarcoidosis. Staining for acid-fast bacilli and fungus was negative. CT-guided aspiration of the hilar lymph nodes revealed noncaseating granulomas, and bronchioalveolar lavage was negative for infectious agents, further supporting the diagnosis of psoriasiform sarcoidosis. Psoriasiform sarcoidosis is a rare and often aggressive form of sarcoidosis, with a poor prognosis due to its multisystem involvement. It accounts for only 0.9% of all cases of sarcoidosis. Differentiation from conditions such as necrobiosis lipoidica, psoriasis, granulomatous mycosis fungoides and interstitial granulomatous dermatitis is difficult, but dermoscopic and histopathological findings are key to making the correct diagnosis. Treatment typically involves systemic steroids for acute disease, with steroid-sparing agents such as methotrexate or hydroxychloroquine used for long-term management. Early diagnosis and appropriate treatment are critical to managing the disease’s progressive nature and avoiding complications.

OBJECTIVE:Cavernous sinus syndrome (CSS) has diverse causes and correctly identifying the underlying pathology is difficult. The study aimed to determine the incremental value of whole-body 18 F-fluorodeoxyglucose (FDG)-PET/computed tomography (CT) in detecting extra-cranial involvement in CSS, to guide biopsy sites; and characterizing cavernous sinus pathologies based on metabolic activity. METHODS:Participants with treatment-naive CSS after clinical assessment and MRI brain were recruited prospectively from July 2022 to December 2023. All the participants underwent whole-body 18 F-FDG-PET/CT, and images were analyzed for the presence, site, extent, and standardized uptake value (SUV max ) and feasibility of biopsy from cavernous sinus and extracranial lesions. Reference standards were histopathology, definite MRI findings, or established diagnostic criteria for immunoglobulin G 4 -related disease, neurosarcoidosis and Tolosa-Hunt syndrome. RESULTS:Data of 54 patients (mean age: 44.8 years) was analyzed. Cavernous sinus lesion was detected in all 54 patients, and 26 (48.1%) patients had extra-cranial lesions. PET-directed biopsies were done from the local extension of FDG-avid cavernous sinus lesions in 20 (37%) and extra-cranial lesions in 12 (22.2%) patients. The final etiological diagnoses were infection in 18 (33.3%), inflammatory disorders in 18 (33.3%), benign neoplasms in 11 (20.5%), and malignancy in seven (12.9%) cases. PET/CT demonstrated significantly lower FDG-avidity in benign cavernous sinus neoplasms (median SUV max : 5.5, IQR: 4.5-8.0) as compared to the infective, inflammatory, and malignant conditions involving the cavernous sinus (median: 15.0, IQR: 10.7-22.4; P  < 0.001). Bony erosions and contiguous paranasal involvement were more frequently associated with infective CSS ( P  < 0.001). CONCLUSION:Whole-body 18 F-FDG-PET/CT effectively identifies extracranial disease in CSS, enables less invasive biopsy site selection, and enhances diagnostic yield while minimizing high-risk intracranial biopsies. 18 F-FDG-PET/CT should be considered in imaging of CSS, especially when definite diagnosis is not established with conventional workup.

BACKGROUND:Autoimmune nodopathies (ANs) are characterized by antibodies targeting nodal and paranodal proteins. Among AN, antibodies targeting neurofascin 186 and/or 140 are rarely reported in children. We describe the clinical features, electrophysiology, histopathology, and treatment outcomes of three children with anti-NF186/140 AN and isolated anti-NF140 AN. METHODS:Retrospective case series. RESULTS:Case 1 was 13-year boy with nephrotic syndrome presented with acute onset asymmetric progressive sensorimotor polyneuropathy with anti-NF140 antibody-positive AN. Cases 2 was a 7.6-year girl with chronic progressive symmetric distal weakness, subacute worsening, and had combined anti-NF186/140 antibody-positive AN. Case 3 was a 3.5-year-old boy with chronic progressive symmetric distal dominant weakness of all four limbs and had bulbar involvement with anti-NF140 antibody-positive AN. All three children had bilateral upper limb tremors. Electrophysiology demonstrated a non-length-dependent mixed axonal and demyelinating pattern of sensorimotor polyneuropathy. Nerve biopsy revealed axonal and mild myelin loss in all three cases, with lymphocytic infiltration in case 1. Treatment included steroids, intravenous immunoglobulins, plasma exchange, cyclophosphamide, and rituximab with graded response and improvement in the Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores. CONCLUSIONS:This case series expands the clinical spectrum of pediatric-onset anti-NF186/140 AN and isolated anti-NF140 AN. Recognition of key clinical clues, including tremors, bulbar involvement, and subacute progression, is essential to distinguish it from chronic inflammatory demyelinating polyneuropathy and Charcot-Marie-Tooth disease to facilitate timely antibody testing and targeted therapy.

Bullous pemphigoid (BP) is known to be associated with various comorbidities such as diabetes mellitus and neurological disorders. However, its association with human immunodeficiency virus (HIV) has been occasionally reported. We hereby report a case of a middle-aged female with BP as well as HIV infection and explore the association between the two conditions.