Cutaneous necrobiotic conditions associated with rheumatoid arthritis: important extra-articular involvement.

Rheumatoid arthritis (RA) presents with various skin conditions as extra-articular manifestations. Rheumatoid nodule is the representative specific skin lesion, histologically exhibiting central necrosis (necrobiosis) surrounded by palisaded macrophages, and being further perivascularly infiltrated with inflammatory cells in the outer regions. Also, there are several skin lesions which histologically show necrobiotic conditions with altered connective tissue degeneration. Necrobiosis may be closely associated with the pathogenesis of RA, i.e., collagen degeneration, recruitment of activated neutrophils, production of various cytokines, and vascular injury. On the other hand, rheumatoid nodule is suggested to develop during therapies with certain drugs such as methotrexate and biologics. These findings may be a clue to understanding the pathomechanisms of rheumatoid nodules. This paper describes several necrobiotic conditions associated with RA, and also discusses the possible pathogenesis and differential diagnosis of rheumatoid nodules. Necrobiosis is the major pathologic condition of cutaneous involvement associated with RA.

[Role of medical treatment for symptomatic leiomyoma management in premenopausal women]. / Place des traitements médicaux : indication, durée, efficacité, chez la femme porteuse de fibromes utérins symptomatiques en période d'activité génitale.

The most frequent symptom with leiomyoma is menometrorrhagia. However, it can be responsible of pelvic pain, dysmenorrhea or urinary and digestive compression when it is particularly voluminous. These recommandations were made in order to review medical management of fibroids. If no therapy is able to have them disappear, various drugs may reduce their related symptoms. Tranexamic acid, non-steroidal anti-inflammatory drugs and high dose of oestrogen may be useful in the management of acute hemorrhagic disorders. Progestin, such as lynestrenol induces small reduction in leiomyoma volume and moderate increase in hemoglobin level before surgery. Pregnane and nor-pregnane may improve menstrual bleeding in short or mild delays. The use of Gonadotropin Releasing Hormone (GnRH) agonists can reduce menstrual bleeding with hemoglobin recovery. Add-back therapy using tibolone seems interesting since secondary effects encountered with GnRH agonists may be reduced. Levonorgestrel-releasing intrauterine system is proven to reduce increased menstrual bleeding and restore hemoglobin level. Aminoglutethimide and fadrozole have been underevaluated to conclude when letrozole seems as efficient as GnRH agonists to reduce leiomyoma volume and provide less hot flushes. Anastrozol is associated with reduction in leiomyomata volume, pain and menstrual bleeding. Mifepristone reduces the size of uterine leiomyomata, improves symptomatology, but could be associated with development of endometrial hyperplasia. SPRM evaluated in females have shown to improve leiomyoma related symptomatology. Danazol could be useful to reduce leiomyoma related symptoms in short terms. Tamoxifen and raloxifen show modest overall benefit. Because of insufficient data concerning fulvestrant, pirfenidone or interferon, their prescription cannot be recommended in patients with leiomyomata.

Necrobiotic xanthogranuloma: a review of 17 cases with emphasis on clinical and pathologic correlation.

OBJECTIVE: To identify correlations between clinical presentation, specific histopathologic findings, and subsequent disease course in patients with necrobiotic xanthogranuloma (NXG). DESIGN: Retrospective review of medical records and histopathologic examination of fixed tissue samples. SETTING: Tertiary care medical center. PATIENTS: Seventeen patients with a diagnosis of NXG established between January 1, 1994, and December 31, 2007. MAIN OUTCOME MEASURES: Description and distribution of clinical lesions, presence of monoclonal gammopathy, multiple myeloma, and correlation with microscopic patterns of skin lesions. RESULTS: Eleven patients (65%) showed involvement of the periorbital area, and the trunk was affected in 8 patients (47%). Twelve patients (71%) had a monoclonal gammopathy; of these, 3 (18%) had multiple myeloma. Histopathologic examination of 12 patients showed findings consistent with NXG, including a bandlike pattern of necrobiotic granulomatous inflammation, atypical giant cells, cholesterol clefts, and plasma cells. No correlations were identified between clinical presentation and specific histopathologic findings. Although most patients had a serum monoclonal gammopathy, staining with antibodies to CD3, CD20, kappa light chains, and lambda light chains showed polytypic lymphocytes and plasma cells in all cases. CONCLUSIONS: The association between NXG and paraproteinemia is well documented and corroborated by this study. However, the skin lesions in NXG represent reactive inflammation and are not associated with the presence of monoclonal plasma cells or multiple myeloma.

An unusual case of granulomatous slack skin disease with necrobiosis.

Granulomatous slack skin disease (GSS) is a very rare form of T-cell lymphoma, with only 52 cases reported in the literature. In the recent World Health Organization-European Organization for Research and Treatment of Cancer consensus classification GSS is considered to be a variant of mycosis fungoides. We describe a patient with GSS and histologic evidence of necrobiosis, which has not been previously reported.

Necrobiotic xanthogranuloma with paraproteinemia; an atypical case.

Necrobiotic xanthogranuloma (NXG) is a rare marker for paraproteinemia. An 86-year-old woman had a one year history of large red-yellow to brown annular plaques involving all limbs. Biopsies showed a non-palisading granuloma with numerous multinucleated giant cells showing prominent elastophagocytosis and extensive areas of necrobiosis throughout the entire dermis. Complete loss of elastic fibers was observed in the central atrophic area of an annular plaque. Small vascular thromboses were also present. Laboratory findings revealed paraproteinemia of IgG-lambda type. Immunohistochemical staining detected the presence of roughly equal numbers of IgG-lambda-and IgG-kappa-staining plasma cells in the dermis. We diagnosed NXG with paraproteinemia with monoclonal gammopathy (IgG-lambda type) of unknown significance.

[Necrobiotic xanthogranuloma with scleroatrophic lichen associated with paraproteinemia]. / Xantogranuloma necrobiótico con paraproteinemia asociado a liquen escleroatrófico.

Necrobiotic xanthogranuloma (Xn) with paraproteinemia is a histiocytoxanthomatosis (non-X histiocytosis) that affects the dermis and subcutaneous tissue of the face and less frequently the trunk and limbs. We present the case of a 58-year-old woman with a previous background of IgG (lambda) paraproteinemia and multiple autoimmune diseases, that associate clinically and histologically typical lesions of Xn on face, neck and limbs and of lichen sclerosus et atrophius (LEA) on skin and mucosae. The treatments performed were ineffective, the Xn lesions followed a chronic and progressive course with increased number, size and ulceration of them. The paraproteinemia has remained stable since it was diagnosed eight years ago. We have not found the association of Xn with paraproteinemia and SAL described in the literature. We review the characteristics of this rare disease and its possible pathogenic mechanisms.

[Long-term course of necrobiotic xanthogranuloma with ocular involvement]. / Langzeitverlauf bei nekrobiotischen Xanthogranulomen mit Augenbeteiligung.

The clinical features of necrobiotic xanthogranuloma (NX) have been presented in a series of case reports, but there are hardly any reports on the clinical long-term course of this rare and usually chronic entity. Therapeutic recommendations are mostly based on individual observations, lacking general therapeutic guidelines. To illustrate a typical chronic and progressive course of NX, we report the case of a 64-year-old woman with periorbital NX, ocular involvement and IgG paraproteinemia. Diagnosed with NX for the first time in 1993, the patient was already presented in this journal in 1995. Since then a series of therapeutic options including medication with dapsone, chlorambucil, interferon-alpha, clofazimine, melphalan, fumaric acid esters, surgical treatment and other physical therapies such as radiation, plasmapheresis, and photodynamic therapy have been applied. None of these therapeutic approaches, however, showed a satisfying long-term effect. At present the patient is undergoing cyclophosphamide-dexamethasone pulse therapy.

Necrobiotic xanthogranuloma associated with choroidal infiltration and syncytial giant cell hepatitis.

A 31-year-old woman developed necrobiotic xanthogranuloma (NXG), a thickened choroid, and syncytial giant cell hepatitis, a previously unreported association. NXG and syncytial giant cell hepatitis may have a common autoimmune pathogenesis.

Chondrodermatitis nodularis helicis as a marker of internal disease [corrected] associated with microvascular injury.

Chondrodermatitis nodularis helicis (CNH) is held to be an idiopathic degenerative process involving the upper dermis of the auricular rim. Chondrodermatitis typically occurs in elderly men where associations with underlying trauma and sun exposure have been postulated as potential inciting triggers. Its association as a marker of systemic disease is not well established. We describe 24 patients with CNH, in whom there were also significant underlying diseases largely associated with vascular injury including those of immune-based etiology and/or conditions which have been previously linked with granuloma annulare, another necrobiotic process of collagen. These patients with concomitant systemic disease were characteristically younger compared to the classic demographics described for CNH. In some cases, chondrodermatitis may represent an ischemic necrobiotic disorder of collagen, potentially defining an important sign of underlying systemic disease in younger patients.

Xantogranuloma necrobiótico sin paraproteinemia / Necrobiotic xanthogranuloma without paraproteinemia

El xantogranuloma necrobiótico es una rara enfermedad granulomatosa que afecta a la piel y a otros tejidos, con frecuencia asociada a disproteinemia. Se presenta el caso de una paciente con sintomatología e histología de xantogranuloma necrobiótico que carecía de alteraciones en el proteinograma y de la típica afectación periocular. La paciente había sido diagnosticada recientemente de leucemia linfática crónica. El caso de nuestra paciente difiere de la mayoría de los descritos en la literatura especializada por asociarse a otro tipo de discrasia sanguínea y no tener afectación periocular. (AU)

Necrobiotic xanthogranuloma with cutaneous and cerebral manifestations. Case report and review of the literature.

Necrobiotic xanthogranuloma (NXG) is a rare inflammatory histiocytic disease of the skin. Xanthogranuloma of the central nervous system is rare and few cases have been reported. To the authors' knowledge, there has been no previously reported case of NXG in which an intracranial lesion was found. This 52-year-old man, in whom NXG with all its cutaneous manifestations had been diagnosed, presented with three episodes of generalized tonic-clonic seizures. A contrast-enhanced computerized tomography scan of his brain revealed a bifrontal, dura-based mass lesion. The lesion was excised and reported to be an NXG that was similar, but not identical to the skin lesions. The patient was placed on a regimen of antiepileptic drug and chlorambucil after surgery.