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Meningitis aséptica, eritema nudoso y eritema anular centrífugo como primera manifestación de una policondritis recidivante
The panniculitides represent a group of heterogeneous inflammatory diseases that involve the subcutaneous fat. The specific diagnosis of these disorders requires histopathological study because different panniculitides usually show monotonous clinical appearance, namely subcutaneous erythematous nodules on the lower extremities. Histopathological study of panniculitis is also challenging because of an inadequate clinicopathological correlation and the evolutionary nature of the lesions. Often, biopsy specimens are taken from late‐stage lesions, which results in non‐specific histopathological findings. In addition, large‐scalpel incisional biopsies are required. However, with adequate biopsy samples a histopathological differential diagnosis between a mostly septal and a mostly lobular panniculitis is straightforward and with adequate clinicopathological correlation, a specific diagnosis may be rendered in most cases of panniculitis. Mostly septal panniculitides with vasculitis include superficial thrombophlebitis and cutaneous polyarteritis nodosa (cutaneous arteritis). Septal panniculitides with no vasculitis may appear as the consequence of dermal inflammatory processes extending to the subcutaneous fat, such as necrobiosis lipoidica, scleroderma, subcutaneous granuloma annulare, rheumatoid nodule and necrobiotic xanthogranuloma, whereas in other cases the inflammatory process involves primarily the connective tissue septa of the subcutis with no participation of the overlying dermis. The most frequent septal panniculitis is erythema nodosum. In contrast, the most common lobular panniculitis with vasculitis is erythema induratum of Bazin (nodular vasculitis). Mostly lobular panniculitides without vasculitis comprise a large list of disorders, including sclerosing panniculitis (lipodermatosclerosis), subcutaneous fat necrosis of the newborn, panniculitis associated with connective tissue diseases, pancreatic panniculitis, 1 ‐antitrypsin deficiency‐associated panniculitis, infective panniculitis and factitious panniculitis. In recent years, several cases of both septal and lobular panniculitis have been described as a consequence of the administration of new drugs, including immune checkpoint inhibitors and BRAF inhibitors used as treatment of metastatic melanoma, tyrosine kinase and Bruton tyrosine kinase inhibitors used for treatment of leukemia and other haematological malignancies and tumour necrosis factor inhibitor drugs.
The panniculitides comprise a group of heterogeneous inflammatory diseases that involve the subcutaneous fat. Histopathological study is required for the specific diagnosis of these disorders, because different panniculitides usually show the same clinical appearance – which typically consists of erythematous nodules on the lower extremities. However, the histopathological study of panniculitis is difficult because of the poor correlation between clinical and pathological findings and the changing microscopic appearances as the lesions evolve. Furthermore, large scalpel incisional biopsies are required in order to evaluate panniculitis fully. From the histopathological point of view, all panniculitides are somewhat mixed, because the inflammatory infiltrate involves both the septa and lobules. However, differentiation between a predominantly septal and a predominantly lobular panniculitis is usually straightforward at scanning magnification on the basis of which subcutaneous structures are the more intensely involved by the inflammatory infiltrate.
Erythema nodosum is the most frequent clinicopathologic variant of panniculitis. The process is a cutaneous reaction that may be associated with a wide variety of disorders, including infections, sarcoidosis, rheumatologic diseases, inflammatory bowel diseases, medications, autoimmune disorders, pregnancy, and malignancies. Histopathologically, erythema nodosum is the stereotypical example of a mostly septal panniculitis with no vasculitis. The composition of the inflammatory infiltrate in the septa varies with age of the lesion. Treatment of erythema nodosum should be directed to the underlying associated condition, if identified.
Erythema nodosum is the most frequent clinico-pathological variant of the panniculitides. The disorder is a cutaneous reaction consisting of inflammatory, tender, nodular lesions, usually located on the anterior aspects of the lower extremities. The process may be associated with a wide variety of diseases, being infections, sarcoidosis, rheumatologic diseases, inflammatory bowel diseases, medications, autoimmune disorders, pregnancy, and malignancies the most common associated conditions. The typical eruption consists of a sudden onset of symmetrical, tender, erythematous, warm nodules and raised plaques usually located on the shins, ankles and knees. Often the lesions are bilaterally distributed. At first, the nodules show a bright red color, but within a few days they become livid red or purplish, and finally they exhibit a yellow or greenish appearance taking on the look of a deep bruise. Ulceration is never seen and the nodules heal without atrophy or scarring. Some clinical variants of erythema nodosum have been described under different names, including erythema nodosum migrans, subacute nodular migratory panniculitis, and chronic erythema nodosum, but probably they are just clinical variants which may all be included within the spectrum of erythema nodosum. Histopathologically, erythema nodosum is the stereotypical example of a mostly septal panniculitis with no vasculitis. The septa of subcutaneous fat are always thickened and variously infiltrated by inflammatory cells that extend to the periseptal areas of the fat lobules. The composition of the inflammatory infiltrate in the septa varies with age of the lesion. In early lesions edema, hemorrhage, and neutrophils are responsible for the septal thickening, whereas fibrosis, periseptal granulation tissue, lymphocytes, and multinucleated giant cells are the main findings in late stage lesions of erythema nodosum. A histopathologic hallmark of erythema nodosum is the presence of the so-called Miescher's radial granulomas, which consist of small, well-defined nodular aggregations of small histiocytes arranged radially around a central cleft of variable shape. Treatment of erythema nodosum should be directed to the underlying associated condition, if identified. Usually, nodules of erythema nodosum regress spontaneously within a few weeks, and bed rest is often sufficient treatment. Aspirin, nonsteroidal anti-inflammatory drugs, such as oxyphenbutazone, indomethacin or naproxen, and potassium iodide may be helpful drugs to enhance analgesia and resolution. Systemic corticosteroids are rarely indicated in erythema nodosum and before these drugs are administered an underlying infection should be ruled out.
The association of relapsing polychondritis with CSF pleocytosis is reported for the first time. Three cases are described in which infectious etiologies of the pleocytosis were excluded by appropriate cultures and serologic studies. We suggest that the finding of CSF pleocytosis in relapsing polychondritis does not merit empiric antimicrobial therapy in the absence of demonstrated infection.
To define the natural history of relapsing polychondritis, the probability of survival and causes of death were determined in 112 patients seen at one institution. By using covariate analysis, early clinical manifestations were identified that predicted mortality. The 5- and 10-year probabilities of survival after diagnosis were 74% and 55%, respectively. The most frequent causes of death were infection, systemic vasculitis, and malignancy. Only 10% of the deaths could be attributed to airway involvement by chondritis. Anemia at diagnosis was a marker for decreased survival in the entire group. There was an interaction between other disease variables and age in determining their impact on outcome. For patients less than 51 years old, saddle-nose deformity and systemic vasculitis were the worst prognostic signs. For older patients, only anemia predicted outcome. The need for corticosteroid therapy did not influence survival.
Aseptic meningitis is a rare complication of relapsing polychondritis. We describe a 60-year-old man who developed a prolonged episode of aseptic meningitis for which no cause could be determined and, that resolved spontaneously. He then developed classic relapsing polychondritis 14 months later. He subsequently had another episode of prolonged meningitis complicated by hydrocephalus. No infectious cause for the meningitis could be determined after extensive investigation including meningeal biopsy. The patient responded to corticosteroids and antituberculous therapy.
In this study we describe clinical and immunogenetic findings in 62 unselected patients with relapsing polychondritis.
In a multicenter study, clinical data of 26 (41.9%) female and 36 (58.1%) male patients were collected. HLA-DR specificities were identified in 60, and the frequencies were compared with those in healthy controls.
The median age at the time of diagnosis was 46.6 years (range 17 to 86). 58 (93.5%) patients had auricular chondritis, 31 (50.0%) ocular symptoms, 35 (56.5%) nasal involvement. Involvement of joints (53.2%), respiratory system (30.6%), skin (24.2%), cardiovascular system (22.6%), central nervous system (9.7%), and kidneys (6.5%) was found as well. 22 (35.5%) patients had associated diseases such as systemic lupus erythematosus or rheumatoid arthritis. Susceptibility to relapsing polychondritis was significantly associated with HLA-DR4 (p < 0.001). There was no difference in the frequency or distribution of DRB1*04 subtype alleles between patients and healthy controls. The extent of organ involvement was negatively associated with HLA-DR6 (p < 0.011).
Immunogenetic findings as well as similarities and overlapping clinical symptoms with other autoimmune or rheumatic diseases suggest that immunological mechanisms play a major role in the pathogenesis of relapsing polychondritis.
Relapsing polychondritis, an uncommon, chronic, multisystem disorder characterized by recurrent episodes of inflammation of cartilaginous tissues, can be life-threatening, debilitating, and difficult to diagnose. This review is based on the authors' experience with 36 patients with relapsing polychondritis who were followed from 1980 to 1997, 30 patients located elsewhere who completed a detailed questionnaire and interview, and a perusal of English-language textbooks and papers located by a systematic search of the MEDLINE database. Relapsing polychondritis can present in a highly ambiguous fashion; therefore, in the authors' series, the mean delay from the time medical attention was sought because of symptom onset until diagnosis was 2.9 years. Although prednisone was the main form of treatment, methotrexate seemed to be of additional value. Survival was much more favorable than previously thought. Greater awareness of relapsing polychondritis would probably lead to earlier diagnosis and better outcomes.
We report a case of relapsing polychondritis with focal sensorimotor seizures, aseptic meningitis, and migratory leptomeningeal enhancement on contrast MRI. These abnormalities on imaging studies correlated accurately with laterality of the patient's seizures, facilitating early aggressive management of his neurologic symptoms.