Relapsing polychondritis is a rare inflammatory disease characterized by recurrent inflammation of cartilaginous structures, mainly of the ears, nose and respiratory tract, with a broad spectrum of accompanying systemic features. Despite its rarity, prompt recognition and accurate diagnosis of relapsing polychondritis is crucial for appropriate management and optimal outcomes. Our understanding of relapsing polychondritis has changed markedly in the past couple of years with the identification of three distinct patient clusters that have different clinical manifestations and prognostic outcomes. With the progress of pangenomic sequencing and the discovery of new somatic and monogenic autoinflammatory diseases, new differential diagnoses have emerged, notably the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome, autoinflammatory diseases and immune checkpoint inhibitor-related adverse events. In this Review, we present a detailed update of the newly identified clusters and highlight red flags that should raise suspicion of these alternative diagnoses. The identification of these different clusters and mimickers has a direct impact on the management, follow-up and prognosis of patients with relapsing polychondritis and autoinflammatory syndromes.

Relapsing polychondritis is a chronic autoimmune inflammatory condition characterized by recurrent episodes of inflammation at the level of cartilaginous structures and tissues rich in proteoglycans. The pathogenesis of the disease is complex and still incompletely elucidated. The data support the important role of a particular genetic predisposition, with HLA-DR4 being considered an allele that confers a major risk of disease occurrence. Environmental factors, mechanical, chemical or infectious, act as triggers in the development of clinical manifestations, causing the degradation of proteins and the release of cryptic cartilage antigens. Both humoral and cellular immunity play essential roles in the occurrence and perpetuation of autoimmunity and inflammation. Autoantibodies anti-type II, IX and XI collagens, anti-matrilin-1 and anti-COMPs (cartilage oligomeric matrix proteins) have been highlighted in increased titers, being correlated with disease activity and considered prognostic factors. Innate immunity cells, neutrophils, monocytes, macrophages, natural killer lymphocytes and eosinophils have been found in the perichondrium and cartilage, together with activated antigen-presenting cells, C3 deposits and immunoglobulins. Also, T cells play a decisive role in the pathogenesis of the disease, with relapsing polychondritis being considered a TH1-mediated condition. Thus, increased secretions of interferon γ, interleukin (IL)-12 and IL-2 have been highlighted. The "inflammatory storm" formed by a complex network of pro-inflammatory cytokines and chemokines actively modulates the recruitment and infiltration of various cells, with cartilage being a source of antigens. Along with RP, VEXAS syndrome, another systemic autoimmune disease with genetic determinism, has an etiopathogenesis that is still incompletely known, and it involves the activation of the innate immune system through different pathways and the appearance of the cytokine storm. The clinical manifestations of VEXAS syndrome include an inflammatory phenotype often similar to that of RP, which raises diagnostic problems. The management of RP and VEXAS syndrome includes common immunosuppressive therapies whose main goal is to control systemic inflammatory manifestations. The objective of this paper is to detail the main etiopathogenetic mechanisms of a rare disease, summarizing the latest data and presenting the distinct features of these mechanisms.

Relapsing polychondritis (RP) is a rare inflammatory disease with significant individual heterogeneity that involves systemic organs. The diagnosis of RP mainly depends on the clinical manifestations; currently, there are no molecular biomarkers routinely evaluated in clinical practice. Biomarkers have diagnostic or monitoring values and can predict response to treatment or the disease course. Over the years, many biomarkers have been proposed to facilitate diagnosis and prognosis. Unfortunately, ideal biomarkers to diagnose RP have not yet been discovered. Most of the molecular biomarkers in RP are immunological biomarkers, with autoantibodies and proteins related to cartilage damage in the blood being the most common. Alterations in some genes (HLA typing and UBA1 somatic mutation) were detected in patients with RP, which could serve as a potential biomarker for the diagnosis of RP. Moreover, proinflammatory cytokines and lymphocyte levels, and certain laboratory tests, have certain values of RP diagnosis and disease activity assessment but lack specificity and sensitivity. This review describes the different types of biomarkers and their clinical correlation with respect to the diagnosis of RP and disease activity. Research on biomarkers and disease pathology is ongoing to identify the ideal biomarkers that are sensitive and specific for RP.

Hypertrophic pachymeningitis (HP) is an inflammatory disorder characterized by intracranial and spinal thickened dura mater, leading to several neurological manifestations including headaches, cranial neuropathies, seizures, and sensorimotor disorders. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a crucial disease that is implicated in the development of immune-mediated HP. HP is observed throughout the clinical course of AAV, and 3%-4% of patients with AAV experience HP as the initial clinical episode. However, patients with ANCA-related HP are unclassifiable in the classification criteria of AAV when HP is the only manifestation, suggesting that ANCA-related HP can be identified as a central nervous system-limited type of AAV. Among patients with AAV, those who develop HP have predominantly been classified as having granulomatosis with polyangiitis (GPA). Myeloperoxidase-ANCA positivity has been more frequently demonstrated than proteinase 3-ANCA positivity in patients with ANCA-related HP. The ear, nose, and throat manifestations, such as otitis media, sinusitis, and mastoiditis, as well as mucous membranes/eyes manifestations including sudden visual loss, are robustly associated with HP in AAV. The histology of thickened dura mater tissues includes fibrotic changes and infiltration of several immunocompetent cells, but the typical findings of GPA, such as granulomatous inflammation with necrotizing vasculitis, are not observed in all patients with ANCA-related HP. Corticosteroids are the first-line therapy for ANCA-related HP, while the concomitant use of immunosuppressive agents including cyclophosphamide, methotrexate, and mycophenolate mofetil, is an ideal strategy for achieving remission. Rituximab is a useful agent in refractory ANCA-related HP.

Relapsing polychondritis (RP) is a rare autoimmune inflammatory disease characterized by recurrent inflammation and destruction of cartilage. Although auricular chondritis is a characteristic finding in RP, it can be difficult to diagnose in the absence of auricular symptoms. A 64-year-old Japanese male was referred to our hospital with fever and respiratory distress. Contrast-enhanced computed tomography (CT) revealed bronchial wall thickening and we suspected RP; however, he had no auricular symptoms and did not meet the diagnostic McAdam criteria for RP, so we used ¹⁸F-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) to search for other cartilage lesions. This analysis revealed FDG accumulation not only in the bronchial walls, but also in the left auricle. Instead of a bronchial biopsy using a bronchoscope, we performed a biopsy of the left auricular cartilage, which is considered a relatively less invasive site. Even though the auricle was asymptomatic, the pathology results revealed chondritis. He was diagnosed with RP, and his symptoms rapidly improved with corticosteroid therapy. A biopsy of asymptomatic auricular cartilage may be useful in the diagnosis of RP. FDG-PET/CT is a powerful tool for the early diagnosis of RP, identifying inflammatory areas even in the absence of symptoms, and guiding the selection of appropriate biopsy sites.

Granulomatosis with polyangiitis (GPA), necrotizing vasculitis of small and medium-sized vessels, is traditionally believed to mainly affect respiratory tract with additional focal kidney involvements as its primary manifestations with a relatively rare annual incidence rate of 20-50 cases per million. Six percent of the affected cases have cardiac involvements; among which, aneurysms comprise the lowest penetrance. By this paper, we aim to cast light on clinical diagnostic and treatment methods of a rare case presentation, a 10-year-old male GPA patient, diagnosed with massive thrombosis at his coronary artery aneurysm. GPA should be considered as differential diagnosis of prolong fever and coronary aneurysms in adolescents.

Relapsing polychondritis (RP) is a rare auto-immune disease that causes progressive destruction of cartilaginous structures. Most cases of pediatric-onset RP were published as a single case report or hand-full case series although the prevalence of RP is unknown. This review aimed to describe the characteristics of pediatric-onset RP in order to provide a comparison between childhood and adulthood features of the disease and to review the experiences of biological agents used in children with RP. In children, the diagnosis of RP is either delayed or overlooked due to low incidence and variability in clinical features. Treatment of RP is challenging due to the recurrent episodic nature of the disease. Different immunosuppressive medications, including steroid and steroid-sparing disease-modifying antirheumatic drugs (DMARDs), such as methotrexate or azathioprine, are used to treat RP. There is no rigorous clinical research to support the use of new therapeutic modalities, including biological agents. It is challenging to protocolize the treatment of pediatric-onset RP due to the rarity of the disease. Corticosteroids are the primary form of therapy. However, DMARDs and biological agents may have a role in treating patients with sustained or refractory disease.

Ankylosing spondylitis, inflammatory bowel disease (IBD), and relapsing polychondritis are immune-mediated inflammatory diseases with variable involvement of lungs, heart and the chest wall. Ankylosing spondylitis is associated with anterior chest wall pain, restrictive lung disease, obstructive sleep apnea, apical fibrosis, spontaneous pneumothorax, abnormalities of cardiac valves and conduction system, and aortitis. Patients with IBD can develop necrobiotic lung nodules that can be misdiagnosed as malignancy or infection. Relapsing polychondritis involves large airways in at least half of the patients. Relapsing polychondritis can mimic asthma in some patients. Medications used to treat these inflammatory conditions can cause pulmonary complications such as infections, pneumonitis, and rarely serositis.

The prevalence of autoimmune diseases has been increasing over the last 20 years. The clinical presentation of this large and heterogeneous group of disorders depends on whether the involvement is organ-specific or non-organ-specific. Dizziness, vertigo, and disequilibrium are common symptoms reported by patients with vestibulocochlear involvement. The association of vertigo and autoimmune diseases has been largely documented, suggesting that autoimmune disorders could be overrepresented in patients with vertigo in comparison to the general population. The aim of this review is to present the recent literature findings in the field of autoimmune-mediated diseases with cochleovestibular involvement, focusing on the clinical presentation, diagnosis, and treatment of immune-mediated inner ear diseases including autoimmune inner ear disease (AIED), Meniere's disease, and bilateral vestibulopathy, as well as of systemic autoimmune diseases with audiovestibular disorders, namely, Behçet's disease, Cogan's syndrome, sarcoidosis, autoimmune thyroid disease, Vogt-Koyanagi-Harada syndrome, relapsing polychondritis, systemic lupus erythematosus, antiphospholipid syndrome, IgG4-related disease, and ANCA-associated vasculitides.

Relapsing polychondritis is an immune-mediated systemic disease characterized by recurrent episodes of inflammation of cartilaginous and proteoglycan-rich tissues, resulting in progressive anatomical deformation and functional impairment of the involved structures. Auricular and nasal chondritis and/or polyarthritis represent the most common clinical features, but potentially all types of cartilage may be involved. Because of the pleomorphic nature of the disease, with non-specific symptoms at the onset, the diagnosis of relapsing polychondritis is often delayed. In this review article we provide a comprehensive look into clinical presentation, laboratory and instrumental investigations, diagnostic criteria, and therapeutic options.

We report a young female who presented with saddle-nose and bilateral cauliflower ear deformities along with pyoderma gangrenosum-like ulcers, digital gangrene and pulselessness. Subsequently, she was found to have bilateral conductive hearing loss, a corneal opacity, mild aortic regurgitation and radiological evidence of cavitary changes in lungs and aortoarteritis. Our patient had a constellation of symptoms which posed a diagnostic challenge. Finally, a diagnosis of relapsing polychondritis with several unusual features was made. Overlap with Takayasu's arteritis and granulomatosis with polyangitis, which has been reported rarely in the literature, cannot be excluded.

Relapsing polychondritis (RPC) is a rare disease with recurrent episodes of inflammation of cartilage tissue leading to fibrosis and organ damage. Despite unknown etiology, there is some evidence of a genetic predisposition. The clinical presentation is heterogeneous and an association with other autoimmune disorders such as rheumatoid arthritis or different forms of vasculitis has been described. All organ systems containing cartilage can be affected, such as ear, nose, joints, trachea, aorta, and coronary arteries. Given the broad spectrum of potential manifestations, a variety of medical specialists may be involved in the management of RPC patients. As establishing the diagnosis of RPC may be difficult, an interdisciplinary approach may be preferable. Treatment options include glucocorticoids, dapsone, disease-modifying antirheumatic drugs, and biologics. Prognosis is as heterogeneous as the clinical picture, depending on the severity of organ damage. In this paper we give an overview of the current knowledge with regard to pathogenesis, clinical picture, diagnosis, and therapy of RPC.

Relapsing polychondritis (RP) is a very rare autoimmune disease characterised by a relapsing inflammation of the cartilaginous tissues (joints, ears, nose, intervertebral discs, larynx, trachea and cartilaginous bronchi), which may progress to long-lasting atrophy and/or deformity of the cartilages. Non-cartilaginous tissues may also be affected, such as the eyes, heart, aorta, inner ear and skin. RP has a long and unpredictable course. Because no randomised therapeutic trials are available, the treatment of RP remains mainly empirical. Minor forms of the disease can be treated with non-steroidal anti-inflammatory drugs, whereas more severe forms are treated with systemic corticosteroids. Life-threatening diseases and corticosteroid-dependent or resistant diseases are an indication for immunosuppressant therapy such as methotrexate, azathioprine, mycophenolate mofetil and cyclophosphamide. Biologics could be given as second-line treatment in patients with an active disease despite the use of steroids and immunosuppressive drugs. Although the biologics represent new potential treatment for RP, very scarce information is available to draw any firm conclusion on their use in RP.

Relapsing polychondritis is a rare multisystemic disease widely accepted as a complex autoimmune disorder affecting proteoglycan-rich structures and cartilaginous tissues, especially the auricular pinna, cartilage of the nose, tracheobronchial tree, eyes, and heart's connective components. The clinical spectrum may vary from intermittent inflammatory episodes leading to unesthetic structural deformities to life-threatening cardiopulmonary manifestations, such as airway collapse and valvular regurgitation. The frequent association with other rheumatologic and hematologic disorders has been extensively reported over time, contributing to define its complexity at a diagnostic and also therapeutic level. Diagnosis of relapsing polychondritis is mainly based on clinical clues, while laboratory data have only a supportive contribution. Conversely, radiology is showing a relevant role in estimating the rate of systemic involvement as well as disease activity. The present review is aimed at providing an update on scientific data reported during the last 3 years about relapsing polychondritis in terms of pathogenesis, clinical features, diagnosis, and new treatment options.

Relapsing polychondritis (RPC) is a unique and rarely observed autoimmune condition regarded as recurrent extensive chondritis of the auricular, nasal, and tracheal cartilages. Moreover, heart, main arteries, skin, and eyes may be involved. Several forms of clinical manifestations may be seen, and the pathogenesis still remains anonymous. A concomitant disease, particularly myelodysplasia or other systemic autoimmune disease can be detected in one-third of the patients with RPC. The treatment of RPC should be considered on personal basis and classified according to disease activity and severity. This study reviews the available data on clinical manifestations, pathogenesis, diagnosis, and therapeutics of the RPC.

Relapsing polychondritis is a rare and potentially fatal autoimmune disease of unknown etiology, characterized by inflammation and destruction of different cartilaginous structures, including the ear, nose, larynx, trachea, bronchi, peripheral joints, eye, heart and skin, with high risk of misdiagnosis. The spectrum of clinical presentations is protean and may vary from intermittent episodes of painful and disfiguring auricular and nasal chondritis or polyarthritis to severe progressive multi-organ damage. A laryngotracheobronchial involvement appears in nearly half of patients and is complicated by local obstructions, which may be life-threatening. A highly medical specialized approach is required for diagnosis of relapsing polychondritis. This review comprehensively examines the literature related to the clinical sceneries of the disease and focuses on both diagnostic tools used in clinical studies and recent findings related to its etiopathogenesis.

Relapsing polychondritis (RP) is a systemic inflammatory disease primarily affecting not only the cartilaginous structures of the ears, nose and tracheobronchial tree but also the joints, the inner ear, the eyes, and the cardiovascular system. RP is an immune-mediated disease during which target antigens are still unknown, but data from human studies and murine models strongly support a role of both Collagen Type II (CII) and matrilin-1 as potential candidates. RP is likely a Th1-mediated disease as serum levels of interferon (IFN)-γ, interleukin [IL]-12, and IL-2 parallel changes in disease activity, while the levels of Th2 cytokines do not. Serum levels of sTREM-1, interferon-γ, CCL4, vascular endothelial growth factor, and matrix metalloproteinases-3 are significantly higher in RP patients than in healthy donors, with sTREM-1 correlating with disease activity. Patients with active RP also have significantly higher levels of MCP-1, MIP-1β, MIF, and IL-8 than controls. These pro-inflammatory chemokines are involved in the modulation and recruitment of monocytes and neutrophils. Altogether, these data suggest that a complex cytokine network orchestrates the recruitment of infiltrating cells in RP lesions. Cytokine modulation using TNFα blockers, rituximab, anakinra, tocilizumab, and abatacept has recently been shown effective in some RP cases but further data are needed. Better understanding of the repertoire of infiltrating cells may provide interesting clues to further define the putative RP auto-antigens. Study of circulating mononuclear cells during RP flares may also provide crucial information about the ongoing cellular trafficking and recruitment processes involved in this rare disease.

Relapsing polychondritis (RP) is a relatively rare disorder, with a high death rate that affects cartilaginous structures. RP can be either primary or secondary as part of autoimmune syndromes. We present a case of RP in a 49-year-old man suffering from cytoplasmic antineurophil cytoplasmic antibodies (cANCA) positive vasculitis, admitted to our hospital with red swollen left ear and painful sternoclavicular joint and larynx. The patient was in remission from the vasculitis but manifested a high cANCA titre indicating vasculitis activity. With his high cANCA titre vasculitis, full manifestation of RP concomitantly occurred. After a successful cortisone treatment for RP, the patient received cyclophosphamide treatment for his vasculitis that resulted in a decrease in cANCA titre and full remission of his RP symptoms.

A 79-year-old man was diagnosed with relapsing polychondritis, from symptoms of bilateral auricular deformity and pigmentation, polyarthralgia, and audiovestibular damage, and from histological examination of the left auricular cartilage. The left auricular cartilage biopsy specimen revealed cartilage destruction with infiltration of plasmacytes expressing IgG4. This case suggests that IgG4 may be involved in the pathogenesis and etiology of relapsing polychondritis.

Relapsing polychondritis (RPC) is a rare autoimmune disease in which the cartilaginous tissues are the target for inflammation and destruction, the associated immune reaction causes inflammation in non-cartilaginous tissues like kidney and blood vessels. This article provides a description of a case of RPC and a review article about the disease.

Atherosclerosis is the main cause of coronary artery aneurysm, however they can be observed in connective tissue diseases such as systemic lupus erythematosus and vasculitis. Kawasaki's disease and polyarteritis nodosa (PAN) are the systemic vasculitis that more often present coronary artery aneurysms. There are descriptions in the literature that small vessel vasculitis such as microscopic polyangiitis and PAN could develop coronary artery aneurysm, which are infrequent in other ANCA-associated vasculitis. Here, we report the case of a 25-year-old man who developed an extensive anterior myocardial infarct. The coronary angiogram showed coronary artery aneurysms, on laboratory ANCA C positivity with elevated levels of anti-proteinase 3 antibodies were present. He was treated with high doses of corticosteroids and cyclophosphamide with resolution of the aneurysms.

Relapsing polychondritis (RPC) is a rare immune mediated disease which is associated with inflammation in cartilaginous tissue throughout the body. Especially the cartilaginous structures of ear, nose, joints and respiratory tract are affected. In around 30% of the cases an association with other diseases especially systemic vasculitis or myelodysplatic syndrome can be detected. The relative rarity of RPC has not permitted clinical trials to determine the efficacy and safety of therapy strategies. Often the medication in current use is largely empiric and based on case reports. Therefore different immunosuppressants such as cyclophosphamide, azathioprine, cyclosporine, mycophenolate mofetil and also new approaches like tumor necrosis factor alpha blockers (TNF-alpha antagonists) have been used for the treatment of severe manifestations of RPC with varying degrees of efficacy. This review gives a close look to clinical manifestation, diagnosis and also therapy options of RPC.

Much like other autoantibodies (eg, anti-double stranded DNA in systemic lupus erythematosus or antiglomerular basement membrane antibodies in Goodpasture's syndrome), antineutrophil cytoplasmic antibodies (ANCA) have provided doctors with a useful serological test to assist in diagnosis of small-vessel vasculitides, including Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and their localised forms (eg, pauci-immune necrotising and crescentic glomerulonephritis). 85-95% of patients with Wegener's granulomatosis, microscopic polyangiitis, and pauci-immune necrotising and crescentic glomerulonephritis have serum ANCA. ANCA directed to either proteinase 3 or myeloperoxidase are clinically relevant, yet the relevance of other ANCA remains unknown. Besides their diagnostic potential, ANCA might be valuable in disease monitoring. In addition, data seem to confirm the long-disputed pathogenic role of these antibodies. Present treatments for ANCA-associated vasculitis are not free from side-effects and as many as 50% of patients relapse within 5 years. Accurate understanding of the key pathogenic points of ANCA-associated vasculitis can undoubtedly provide a more rational therapeutic approach.

Microscopic polyangiitis (MPA) is a systemic disorder characterized by inflammation of small vessels mainly affecting the kidneys and lungs. We describe a 72-year-old woman who developed multiple cartilage involvements as well as major manifestations of MPA. The left ear biopsy demonstrated cartilaginous inflammation and small vessel vasculitis. She also had conjunctivitis, hearing impairment, interstitial lung disease, glomerulonephritis with vasculitis and mononeuritis multiplex. Serological examinations revealed a positive antineutrophil cytoplasmic antibody (PR-3 ANCA). Cyclophosphamide and oral corticosteroid therapy was instituted and remission achieved. Due to lacks of nasal and bronchial involvements, as well as the evidence of auricular vasculitis, we concluded that her findings mimicking relapsing polychondritis developed as systemic manifestations of MPA.

Review of relapsing polychondritis (RP) and its association to chronic hepatitis C virus (HCV) infection and mixed cryoglobulinemia.

A case of RP associated with HCV infection is reported. The English language medical and scientific literature was reviewed for RP, hepatitis C, and its relation to other connective tissue diseases from February 1966 to January 2003 using MEDLINE.

RP is an uncommon, multisystem disease of unknown etiology characterized by recurrent inflammation of cartilaginous and related tissues, being associated with other diseases in 30% to 35% of cases. HCV infection is a systemic illness with a propensity to trigger or exacerbate autoimmune disorders: eg, essential mixed cryoglobulinemia, membranoproliferative glomerulonephritis, and leukocytoclastic and systemic vasculitis. We could find no previous report of an association between RP with HCV and mixed cryoglobulinemia. Treatment with interferon gamma and ribavirin (IR) not only induced an undetectable viral load, but also resolved symptoms of RP.

We report a patient with RP, HCV, and mixed cryoglobulinemia. It is unknown if there is a cause-effect or chance relationship. Treatment with IR improved the symptoms of RP. It is not known whether the effects of IR were directly on the RP or suppressed RP indirectly through the actions on the viral load or active hepatitis.

Relapsing polychondritis is a unique, rare autoimmune disorder in which the cartilaginous tissues are the primary targets of destruction but the immune damage can spread to involve noncartilaginous tissues like the kidney, blood vessels, and so forth. The manifestations of the disease can take many different forms and the pathogenesis is still unclear. It may occur in a primary form or it may be associated with other disease states. This article summarizes important aspects of the disease with a focus on recent information regarding clinical manifestations, disease associations, pathogenesis, and advances in therapeutics.

Dermatologic manifestations of relapsing polychondritis (RP) have been relatively poorly studied compared to other manifestations. In this study we describe dermatologic manifestations in a large series of patients with RP and the corresponding pathologic findings. In this retrospective, single-center review of 200 patients diagnosed with RP according to Michet's criteria, we analyzed separately those suffering from associated diseases with potential dermatologic involvement or chronic dermatitis. Skin or mucosal biopsies taken from 59 patients were examined without knowledge of the clinical data. Among the 200 patients with RP, 73 had chronic dermatitis or associated diseases with potential dermatologic involvement, especially hematologic disorders (n = 24) and connective tissue diseases (n = 22). Among the other 127 patients, 45 (35.4%) had dermatologic manifestations: aphthosis (n = 21; oral in 14 and complex in 7), nodules on the limbs (n = 19), purpura (n = 13), papules (n = 10), sterile pustules (n = 9), superficial phlebitis (n = 8), livedo reticularis (n = 7), ulcerations on the limbs (n = 6), and distal necrosis (n = 4). Dermatologic manifestations were the presenting feature of RP in 15 cases (12%), and appeared concomitantly (n = 23) or not (n = 22) with attacks of chondritis. Histologic findings included vasculitis (n = 19, leukocytoclastic in 17 and lymphocytic in 2), neutrophil infiltrates (n = 6), thrombosis of skin vessels (n = 4), septal panniculitis (n = 3), and minor changes (n = 2). Patients with and without dermatologic manifestations did not differ with regard to male/female ratio; age at RP onset; frequency of auricular, nasal, or tracheobronchial chondritis; or frequency of rheumatologic, ocular, audiovestibular, renal, arterial, or venous involvement. The frequency of dermatologic manifestations (91% versus 35.4%; p < 0.0001), sex ratio (18 male/4 female versus 44 male/83 female, p < 0.0001), and age at first chondritis (63.3 +/- 14 yr versus 41.4 +/- 17 yr; p < 0.0002) were significantly higher in the 22 patients with myelodysplastic syndrome than in the 127 patients without any associated disease. In conclusion, although dermatologic manifestations occur frequently in patients with RP, especially in association with myelodysplasia, they are nonspecific and sometimes resemble those observed in Behçet disease or inflammatory bowel diseases. Their presence in the elderly warrants repeated blood cell counts to detect a smouldering myelodysplasia.

ANCA mainly recognize proteinase 3 (cytoplasmic fluorescence) in Wegener's granulomatosis and myeloperoxidase (perinuclear fluorescence) in other types of vasculitis. A causative role of ANCA seems not obvious because: a) active generalized Wegener's granulomatosis may exist with no detectable ANCA, b) ANCA titres don't reliably parallel clinical activity and c) of the increasing diversity of clinical situations where ANCA are described. Nevertheless, some lines of evidence point to a pathogenetic role of ANCA, especially in vascular lesions genesis: a) ANCA may prevent inactivation of antigenic proteases by antiproteases, b) translocation at the outer membrane of intracellular antigens make them accessible to ANCA, c) activation of polymorphonuclear leucocytes and increase of their aggregation and cytotoxicity to endothelial cells are specifically induced by ANCA, d) proteinase 3 and myeloperoxidase may adhere to the endothelial cell membrane and then be recognized by ANCA, e) a specific T-lymphocyte response to ANCA antigens could be elicited in Wegener's granulomatosis and f) an in vivo model of ANCA-related glomerulonephritis has recently been established.