Hemophagocytic Lymphohistiocytosis (HLH) and Sweet Syndrome are two hyperinflammatory conditions, which can be genetic or precipitated by infections, primary immunodeficiencies, autoimmune conditions, or certain therapies and transplants. HLH results because of a exaggerated response by the dysregulated CD+ T cells, leading to widespread activation of macrophages, resulting in hemophagocytosis and excessive, organ-damaging inflammation. Sweet syndrome is another uncommon condition, presenting as sudden onset of painful, edematous, and erythematous papules, plaques, or nodules on the skin, precipitated by the same. It is unusual for them to present sequentially, so herein we present a case of two distinct hyperinflammatory syndromes, Epstein Bar Virus-triggered HLH followed by COVID-19 triggered necrotizing Sweet Syndrome, both occurring in a 53-year-old patient with history of remote history of juvenile idiopathic arthritis within a short time span.

Rheumatoid arthritis (RA) is a chronic autoimmune systemic disease affecting mostly the small joints of the hands and feet. Extra-articular manifestations (EAMs) comprise the involvement of the skin, eyes, heart and lung. Among them, subcutaneous rheumatoid nodules (RN) are a common manifestation of systemic disease. However, disorders such as rheumatoid nodulosis, multicentric reticulohistocytosis (MRH) and others present subcutaneous nodules, similar to those seen in RA patients. A 41-year-old woman with a 10-year history of untreated RA, presented complaining of pain and tenderness in the small joints of the hands and feet. Past medical and family history were unremarkable. She presented swelling and tenderness on all metacarpophalangeal joints (MCPs) bilaterally and had multiple widespread subcutaneous RN affecting almost all the fingers of the hands, as well as, the Achille's tendons in a symmetrical manner. She had elevated levels of acute phase reactants and high titres of autoantibodies. Hand x-rays revealed severe erosive changes affecting all MCPs joints bilaterally. Thus, in this review we discuss the differential diagnosis of subcutaneous RN and their role in RA disease activity. This is an educational case of a patient with RA and extensive subcutaneous RN affecting the upper and lower extremities. To this end, physicians must be familiar and recognise early these signs which reflect RA disease activity and treat appropriately.

Connective tissue diseases comprise a spectrum of autoimmune disorders characterized by chronic inflammation and immune-mediated injury affecting the skin, vasculature, cartilage, and internal organs. The external ear, owing to its unique composition of elastic cartilage, thin dermis, and end-arterial vasculature, represents a visible and diagnostically informative site of connective tissue disease involvement. Auricular lesions may manifest as erythematous chondritis, purpura, necrosis, nodules, or sclerotic plaques, often providing dermatologists with early clinical clues to systemic disease. This review focuses on the dermatologic and histopathologic features of ear involvement in connective tissue diseases, including relapsing polychondritis, systemic lupus erythematosus, rheumatoid arthritis, granulomatosis with polyangiitis, levamisole-adulterate-cocaine-associated anti-neutrophil cytoplasmic antibody vasculitis, dermatomyositis, systemic sclerosis, Cogan syndrome, and mixed connective tissue disease. Although audio-vestibular dysfunction may accompany these diseases, the emphasis here is on the cutaneous, vascular, and chondral manifestations visible to dermatologists,with correlation of the histopathology with clinical morphology. Enhanced recognition of auricular signs can facilitate earlier diagnosis, guide biopsy, and prompt appropriate multidisciplinary evaluation.

Subcutaneous granuloma annulare (SGA) is a rare skin condition that has overlapping features with rheumatoid nodules due to similar clinical and histological features. A 42-year-old female with a history of celiac disease and a family history of rheumatoid arthritis developed progressively painful nodules on her right hand. She was initially thought to have rheumatoid arthritis, but her serological markers were negative, and an incisional biopsy revealed palisaded granulomas with central mucin and necrobiotic collagen that led to a diagnosis of SGA. Differentiating between these two conditions is important because rheumatoid nodules require immunosuppressive therapy due to systemic inflammation, while SGA is a self-limiting benign condition. This case highlights the need for a biopsy of atypical subcutaneous nodules and the importance of combining clinical, pathological, and interdisciplinary expertise to ensure accurate diagnosis and the best patient care.

Pancreatic panniculitis is a rare cutaneous manifestation of pancreatic disease, most commonly occurring in patients with acute or chronic pancreatitis or pancreatic neoplasms. In most reported cases, pancreatic pathology is recognized before or concurrent with the onset of skin lesions; less commonly, panniculitis precedes the diagnosis. Histology demonstrates a lobular panniculitis with saponified fat necrosis and anucleate "ghost" adipocytes, findings that are pathognomonic. Clinically, pancreatic panniculitis presents as tender subcutaneous nodules, most often on the lower extremities, and may be accompanied by systemic manifestations such as fever and inflammatory arthritis. We report 2 cases of pancreatic panniculitis occurring in patients without abdominal pain.

Blastomycosis is a dimorphic fungal infection caused by Blastomyces dermatitidis and related species, classically presenting with pulmonary and cutaneous involvement. Musculoskeletal manifestations, particularly monoarthritis, are rare and diagnostically challenging. We present the case of a previously healthy 41-year-old man who developed nodular skin lesions, cough, pulmonary nodules and persistent left knee arthritis, initially thought to be due to pseudogout. The diagnosis of disseminated fungal infection was suggested by CT scan, skin biopsy, and confirmatory fungal culture that grew Blastomyces dermatitidis. This case highlights the atypical pattern of joint involvement, the need to expand the differentials as dictated by clinical signs, the role of multidisciplinary collaboration, and the diagnostic utility of skin biopsy and fungal culture.

Dupuytren's disease is a fibroproliferative disorder of the palmer fascia (PF) characterised by flexion contractures in the hand. Dupuytren's disease can be treated surgically, but disease recurrence rates are high, potentially due to continual production of matrisomal proteins. Here, metabolic labelling and proteomics identified differences in the new synthesis and composition of matrisomal proteins between Dupuytren's tissue and normal PF. Dupuytren's tissue actively synthesised type I collagen, fibronectin (FN1), matrix metalloproteinases-2 and -3 (MMP2, MMP3) and tissue inhibitor of metalloproteinases 2 (TIMP2). Both tissues actively synthesised insulin-like growth factor binding protein 7 (IGFBP7). Label-free analysis implicated the transforming growth factor-β (TGFβ) pathway in the matrisomal profile of Dupuytren's tissue. The effect of TGFβ isoforms on COL1 mRNA expression was first tested in cultured young and aged equine tenocytes. COL1A1 mRNA responded to treatment with all TGFβ isoforms and was more highly expressed in cells from aged samples. In aged human cells, COL1A1 and COL1A2 mRNA was higher in cells derived from Dupuytren's tissue than normal PF and in response to TGFβ1, but no changes in COL1A1 or COL1A2 CpG methylation were detected. TGFβ1 treatment only resulted in increased type I collagen protein accumulation in the media of Dupuytren's nodule cells. In three-dimensional cultures, COL1A1 mRNA was lower in normal PF than in Dupuytren's cells, but TGFβ1 treatment only increased type I collagen accumulation in the media of normal PF cultures, and TGFβ1 inhibition did not alter new collagen protein synthesis. TGFβ1 inhibition in Dupuytren's tissue explants did not alter the proportion of homotrimeric type I collagen, nor was this changed in skin or tendon of the tight-skin (TSK) mouse, a naturally occurring model of indirect TGFβ1 activation. Therefore, the role of TGFβ in Dupuytren's disease may be predominantly related to myofibroblast phenoconversion and contractility rather than directly altering collagen protein synthesis. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

BACKGROUND: Pure neuritic leprosy (PNL) is an uncommon clinical form of leprosy characterized by nerve involvement without skin lesions, making diagnosis challenging. Type II lepra reaction (erythema nodosum leprosum, ENL) is rarely associated with PNL. CASE PRESENTATION: We report a 39-year-old male from Harar, Ethiopia, who presented with a 10-month history of progressive numbness, tingling, and weakness in the left hand. Clinical examination revealed thickened and tender ulnar nerve, sensory loss, hypothenar atrophy, and clawing of the ring and little fingers. Nerve conduction studies confirmed severe ulnar neuropathy, and ear-lobe biopsy was Negative for Bacilli establishing the diagnosis of PNL with Grade II disability based on clinical basis according to WHO classification after taking in account that the patient was on Anti-TB during the biopsy test. The patient was started on standard World Health Organization (WHO) multidrug therapy (MDT). After three weeks, he developed fever, arthritis, and tender supraorbital nodules consistent with Type II lepra reaction. He was managed with corticosteroids, physiotherapy, and continuation of MDT. Systemic symptoms subsided, though neurological deficits persisted. CONCLUSION: This case highlights the diagnostic challenges of PNL in the absence of skin lesions and the rare occurrence of Type II lepra reaction in this form. Early recognition, integration of advanced diagnostic tools, and timely physiotherapy are crucial to minimize disability in endemic settings.

A 58-year-old man presented with an enlarging painful ulcer on his left medial knee. He had a history of psoriatic arthritis, treated with methotrexate and adalimumab for the last 5 years. He had travelled to over 20 countries in the past 2 years, and his hobbies included scuba diving and seawater/freshwater swimming. He recalled freshwater swimming in a cave lake in Brazil 1 year prior. Subsequently, he developed small erythematous papules on each knee with rapid resolution on the right knee. The left knee lesion slowly enlarged, and he sought medical attention in Ireland 9 months later. He received antibiotics and topical steroids, and was switched from adalimumab to infliximab for a presumed diagnosis of pyoderma gangrenosum. The lesion's growth accelerated over 8 weeks, leading to an acute presentation to the Emergency Department with severe pain and limited mobility. On examination, he had a 20 × 10 cm erosive plaque on his left knee with an exudative base and a ragged erythematous edge. He also had a 2.5 × 2 cm ulcerative lesion on his right flank and a hyperpigmented patch on his right knee. He denied fevers or systemic symptoms. Interferon-γ release assay was positive. A skin biopsy from the left leg demonstrated ulceration, mixed inflammation and underlying dermal necrosis. Necrotizing granulomas were seen, and both auramine and Ziehl-Neelsen stains were positive for abundant acid-fast bacilli. Skin biopsy from the right flank showed similar findings. A mycobacterial culture was incubated at 30°C and after 4 weeks, Mycobacterium marinum was identified. Mycobacterium marinum is a free-living, slow-growing, nontuberculous mycobacterium found in cold and warm fresh and saltwater environments. It can cause a tuberculosis-like disease in fish and can opportunistically infect humans when injured skin is exposed to a contaminated aqueous environment. The typical presentation is a 'fish tank granuloma': nodules, plaques or ulcerated lesions that spread in a sporotrichoid pattern along lines of lymphatics, commonly on the upper limb. This case represents a highly unusual cutaneous M. marinum presentation, with noncontiguous ulcerative lesions in an immunocompromised host. The diagnostic delay highlights the challenges of recognizing atypical nontuberculous mycobacterial infections, particularly in patients who are immunosuppressed.

Lofgren syndrome is an acute and pathognomonic form of sarcoidosis characterized by fever, hilar lymphadenopathy, arthritis, and erythema nodosum (EN). We report a 35-year-old female patient from Ethiopia who presented with a 4-day history of arthritis involving bilateral ankles, knees, and wrists associated with fever and skin lesions typical of EN. Chest imaging (X-ray and computed tomography (CT) scan) revealed bilateral hilar and mediastinal lymphadenopathy as well as perilymphatic nodules in the mid and upper zones of both lungs. Workup for alternative diagnoses, including tuberculosis, was negative. After the diagnosis of Lofgren syndrome was made, she was started on a low dose of prednisolone, which resulted in a prompt and marked improvement in her symptoms.

An 82-year-old man with a history of hypertension, thyroid nodule, and parkinsonism on carbidopa/levodopa was referred for a sudden eruption of scattered purpuric macules. He noted fatigue, weakness, ankle swelling, abdominal fullness, headaches, lapses in memory, and dysphasia. On physical examination, he had thin and atrophied upper extremities and central obesity, as well as nonblanching red to purple macules on the lower abdomen and ecchymosis on bilateral arms. The patient denied the use of any corticosteroids. Lab workup showed an abnormally high post-dexamethasone cortisol level, which raised suspicion for Cushing syndrome. Further inquiry into the patient's medication and supplement history revealed that he was consuming Artri King, a supplement marketed for the treatment of joint pain and arthritis. Artri King can lead to numerous dermatological manifestations akin to endogenous Cushing syndrome such as thin skin, easy bruising, and purple striae. This case illustrates the potential risks of over-the-counter dietary supplements, which often circumvent the strict Food and Drug Administration regulations applied to prescription medications, posing significant health hazards to users. There is critical need for transparency and regulation of supplements.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by painful nodules, abscesses, and draining tunnels in areas such as the axillae, groin, and inframammary regions. It typically emerges in early adulthood, with a global prevalence of approximately 1%, though regional variations exist. HS significantly affects patients' quality of life and imposes considerable socioeconomic burdens. It is frequently associated with metabolic syndrome, inflammatory arthritis, and inflammatory bowel disease, reflecting its underlying systemic inflammatory nature. The pathogenesis of HS involves innate immune mechanisms, including macrophages, neutrophils, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and granulocyte colony-stimulating factor, alongside adaptive immune responses mediated by T cells (IL-17, interferon [IFN]-γ) and B cells, which contribute to autoantibody formation and tertiary lymphoid structures. Chronic inflammation results in irreversible tissue damage, tunnel formation, and severe scarring. Treatment strategies vary based on disease severity. Early inflammatory stages benefit from pharmacological therapies, while later stages require a combination of medical and surgical interventions, with surgery often necessary for advanced cases. The introduction of targeted biologic therapies, including TNF-α (adalimumab) and IL-17 inhibitors (secukinumab, bimekizumab), has expanded treatment options beyond traditional antibiotic regimens. Effective management focuses on early intervention to prevent irreversible damage, control symptoms such as pain, and address systemic comorbidities. A timely diagnosis, along with a multidisciplinary and personalized approach, is essential for improving patient outcomes and quality of life.