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The patient presented with hyperkeratotic-crusted plaques on her legs that had been present for 6 months. Previously, she had had various efflorescences ranging from palpable purpura on the lower legs and an erosive plaque on the tip of the nose to psoriasiform lesions, folliculitis and oral mucosal erosions. In addition, she had been suffering from intermittent bone and joint pain due to chronic non-bacterial osteomyelitis (CRMO) for 3 years and had been taking naproxen continuously. Moreover, she had also been suffering from recurrent right ear canal inflammation with otorrhea for a year. Both lower legs showed disseminated, lividly erythematous, centrally atrophic plaques with an overlying hemorrhagic, fibrinous crust (Figure 1). Additionally, an erythematous plaque was found on the hairy scalp. A sample biopsy from the lower leg showed granulomatous dermatitis with multinucleated giant cells and palisade granulomas around necrotic degenerated connective tissue (Figure 2). No pathogen was detected by histochemistry (PAS, Ziehl-Neelsen stain). Your diagnosis? … Diagnose: Granulomatose mit Polyangiitis Granulomatosis with polyangiitis Laboratory analysis revealed a slightly elevated ESR with normal CRP. Positive PR3-ANCAs were found in immunoserology, the remaining laboratory results were unremarkable. The painful bone changes (forefoot, pelvis, elbow) were classified as CRMO, independent of granulomatosis with polyangiitis (GPA), correlating clinical findings and MRI imaging results. During imaging for CRMO, a pulmonary round focus in the right upper lobe was incidentally discovered, appearing as a cystic hemorrhagic lesion on chest MRI. In addition, there were multiple, suppurative nodules in both upper lobes of the lung and prominent perihilar lymph nodes. Endobronchial biopsies showed a granulomatous inflammatory infiltrate with eosinophils and obliterated, intraparenchymal, small arterial vessels (Figure 3). With the recurrent otitis externa on the right side with bloody and purulent otorrhea, a crusty mucosal swelling of the external auditory canal was found; CT revealed bone erosion at the base of the auditory canal. Local steroid and antibiotic therapy was administered and the ear canal was repeatedly cleaned by a specialist. An interdisciplinary inflammation board (rheumatology, pediatrics, dermatology) ultimately made the diagnosis of GPA. To induce remission of the generalized disease with lung involvement, methotrexate 15 mg/week s.c. combined with 45 mg prednisolone p.o. (1 mg/kg body weight) was initiated with a tapering regimen over a period of months. In addition, four rituximab cycles (540 mg i.v. on days 1 and 7) were applied. Cotrimoxazole 960 mg/week was also administered to protect against infection (Pneumocystis jirovecii). Currently, the GPA is stable and the patient shows no systemic symptoms or functional impairment. In the course of the disease, the CMRO was clinically and radiologically halted. The skin changes have healed with scarring. MTX 7.5 mg/week and prednisolone 5 mg/d are currently being administered to maintain remission. GPA (formerly: Wegener's granulomatosis) is a rheumatological disease associated with necrotizing, ANCA-associated vasculitis of the small to medium-sized vessels along with granulomatous inflammation of the respiratory tract. The disease usually manifests in the 40th-50th year of life, without gender predilection.1 The localized stage typically begins with inflammation of the upper respiratory tract with oral or nasal ulcers with purulent-bloody sinusitis and rhinitis as well as chronic otitis. Patients often also suffer from fever, not infrequently also from arthralgias and arthritides. In the generalized stage, systemic vasculitis manifestations usually occur with involvement of the kidneys (necrotizing glomerulonephritis) and/or lungs (pulmonary, non-caseating granulomas and/or alveolar haemorrhages). Skin manifestations are found in around 20% of cases of the disease, including ulcerations, palpable purpura, acral necrosis, acneiform papules and subcutaneous nodules, which are often clinically unspecific and suggest other entities.1, 2 The presence of antineutrophil cytoplasmic antibodies (ANCA) suggests a pathogenetic autoimmune mechanism. Antineutrophil cytoplasmic antibodies can potentially lead to necrotizing vasculitis by releasing reactive oxygen radicals and proteases. Granulomas form alongside the vasculitis. The process of granuloma formation is not fully understood, but involvement of T-cell hyperactivity has been suggested.3 In 90% of patients in the generalized stage, a positive cANCA (PR3) can be detected, which correlates with disease activity.3 In the presence of serologically and histologically confirmed ANCA-associated vasculitis, which constitutes a subgroup of primary systemic vasculitis according to the Chapel Hill consensus conference, the following differential diagnoses can be considered depending on the clinicopathological features: GPA, eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA).4, 5 In the differential diagnosis of the present case, particular consideration was given to the absence of granulomatous organ infiltrates in the MPA and the presence of blood eosinophilia and asthma in EGPA,4 which was not the case in our patient. Based on the ACR/EULAR classification criteria revised in 2022, the present case has a cumulative score of 9 (positive PR3-ANCAs, pulmonary round focus on thoracic imaging and granulomatous inflammation on histology). In the diagnosis of small/medium vessel vasculitis, a cut-off value of ≥ 5 points allows classification as GPA.6 Biopsies of the affected organ systems are decisive, with GPA often showing connective tissue necrosis surrounding palisade granulomas and multinucleated giant cells as well as vasculitically altered vessels.2, 4 Therapy depends on the stage and activity of the disease. For the induction of remission, either rituximab (RTX) or methotrexate (MTX) combined with glucocorticoids (GC) is recommended for active GPA that is not organ- or life-threatening, while RTX or cyclophosphamide (CYC) combined with GC is recommended for patients with organ- or life-threatening disease.5 As a relatively new recommendation for remission induction while reducing GC doeses, the oral C5aR inhibitor avacopan combined with RTX or CYC may also be considered.5 In the generalized stage with organ failure (usually renal failure), plasma exchange is recommended in addition to CYC plus GC.5 For maintenance of remission, the primary recommendation is RTX (treatment duration: 24–48 months); alternatively, MTX or azathioprine.5 Treatment of refractory cases remains challenging. Studies have shown good efficacy of RTX in refractory vasculitis manifestations, with a high rate of non-responders regarding granulomatous manifestations.7 Approximately 4 years passed between the appearance of the first manifestations and diagnosis and appropriate initiation of treatment. Nowadays, GPA is diagnosed on average after 4 months, which means that in our case diagnosis took an unusually long time.8 In the case of unclear skin changes with variable clinical manifestations, especially if histological evidence of granulomatous dermatitis is found, extracutaneous symptoms reported by the ENT, nephrology and pulmonology specialties should be specifically investigated so that GPA is not overlooked. None.
Roßner et al. (Thu,) studied this question.