[Cutaneous granulomatosis]. / Granulomatoses cutanées.

Granulomatous skin diseases represent a large group of reactive dermatoses occurring in response to different stimuli and whose skin biopsy is characterized by a granulomatous inflammatory infiltrate. By their very heterogeneous clinical presentation, it seems difficult to distinguish them and make their diagnosis. Clinically, it may be useful to separate localized forms of disseminated forms of cutaneous granulomatosis, although this distinction is often artificial. We will discuss here the main forms of localized and disseminated cutaneous granulomatosis, and, in light of recent literature data, mention different therapeutic options in each case.

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.

Necrobiosis and T-lymphocyte infiltration in retrieved aseptically loosened metal-on-polyethylene arthroplasties.

BACKGROUND AND PURPOSE: Soft tissue necrobiosis and T-lymphocyte infiltration within the periprosthetic soft tissue have been linked to a suggested hypersensitivity reaction of the delayed-type following the metal-on-metal arthroplasty. While we observed both synovial necrobiosis and lymphocyte infiltrates in synovial tissues with failed metal-on-polyethylene prostheses, we hypothesized that both findings are unspecific for metal-on-metal bearing coupes. Thus, we wished to quantify the extent of necrobiosis and the amount of T-lymphocyte infiltration in aseptically loosened metal-on-polyethylene prostheses. MATERIALS AND METHODS: We analyzed 28 consecutive synovial biopsy specimens obtained at revision surgery of aseptically loosened metal-on-polyethylene prostheses (19 hips and 9 knees) and quantified both the extent of necrobiosis vertically and the density of CD3+, CD4+, and CD8+ lymphocytes within the joint capsular tissue. We excluded patients with inflammatory skeletal disease or with a history of metal hypersensitivity. RESULTS: We found necrobiosis in 23 of 28 cases and it was most often connected with the superficial portions of the synovium. Necrobiosis of deeper tissues was seen in 8 specimens and it was strongly associated with superficial necrobiosis. While CD3+ lymphocytes were detected in each biopsy, 4 cases with more than 300 CD3+ lymphocytes were identified in the group of 26 cases that presented with more than 100 CD3+ lymphocytes within one high-power field. 16 cases with more than 100 CD3+ lymphocytes also showed concomitant superficial necrobiosis of the synovium. In the inflammatory infiltration of periprosthetic synovium, CD8+ lymphocytes predominated over CD4+ cells. INTERPRETATION: Synovial necrobiosis and infiltration of T-lymphocytes are common findings in tissues around aseptically loosened metal-on-polyethylene arthroplasty in patients without a clinically suspected metal hypersensitivity reaction. Thus, neither necrobiosis nor infiltration of T-lymphocytes should be considered to be specific for failed metal-on-metal bearings or metal hypersensitivity reaction.

The histopathological study of osteoporosis.

The osteoporosis is characterized by the imbalance between the activity of the osteoblasts, the bone forming cells, and the osteoclasts, the cells that resorb the bone tissue, imbalance that favors the osteoclasts. As a conclusion, in the case of osteoporosis, for the same volume, the bone is less compact and more fragile. The objective of our study is to make a histological evaluation of the different elements of the bone tissue in many 47 bone samples: 27 bone fragments were collected from the head and the femoral head of patients who required hip arthroplasty and 20 bone fragments were collected from the vertebral body of dead patients. The results of our study emphasized the thinned trabeculae of the bone that lost continuity, the preferential resorption of the horizontal trabeculae, the consecutive trabecular anisotropy and the reduction of the trabecular connectivity with enlarged areolae and the adipose degeneration of the marrow. One notices in the osteoporosis a reduction of the trabecular network connectivity directly proportional with the stage of the illness; thus, we determined a strong reduction of the trabecular connectivity in advanced osteoporosis stages. The growth aspects of the medular adiposity, associated with the intratrabecular connectivity concurs to highlight the functional connection between bone and marrow. The diminution of the medullar cellularity together with its enrichment in fat cells has negative outcomes on the bone.

An unusual skin presentation of necrobiotic xanthogranuloma.

A well appearing 73-year-old Caucasian lady presented with a long-standing history of yellowish atrophic lesions on her limbs and trunk. The lesions were asymptomatic. These were found to be consistent with the diagnosis of Necrobiotic Xanthogranuloma (NXG) on histology. The reported patient did not have the characteristic skin changes and instead had unusual lesions reminiscent of morphoea not described in the literature. She reported no associated systemic symptoms.

Generalized necrobiotic xanthogranuloma successfully treated with lenalidomide.

Necrobiotic xanthogranuloma (NXG) presents a therapeutic challenge to clinicians. Generalized NXG has limited treatment options. A patient presented to the authors with generalized NXG associated with monoclonal gammopathy of unknown significance (MGUS), a plasma cell dyscrasia considered to be a precursor to multiple myeloma. The patient was treated with lenalidomide, a derivative of thalidomide with efficacy in treatment of multiple myeloma. Resolution of paraproteinemia was associated with resolution of NXG.

Necrobiotic xanthogranuloma without paraproteinaemia: marked improvement with psoralen ultraviolet A treatment.

Necrobiotic xanthogranuloma (NXG) is a rare granulomatous condition that is often associated with a paraproteinaemia and in some cases multiple myeloma. Treatment is therefore aimed at the underlying associated haematological abnormality. However, isolated NXG cases have been reported. We report a case of isolated NXG that responded very well to systemic psoralen ultraviolet A (PUVA) treatment. The rationale for this treatment was the successful use of PUVA treatment in other necrobiotic conditions such as granuloma annulare and necrobiosis lipoidica.

Neutrophilic urticarial dermatosis: a variant of neutrophilic urticaria strongly associated with systemic disease. Report of 9 new cases and review of the literature.

We conducted the current study to define within the spectrum of the neutrophilic dermatoses a group of patients with an urticarial rash clinically and a neutrophilic dermatosis histopathologically. We reviewed the literature on neutrophilic urticaria and we report here a series of patients with this unique presentation. We reviewed all cutaneous biopsies submitted to our department between 2000 and 2006 in which histopathologic evaluation was compatible with this entity. We then retrieved the patient medical records and obtained information about follow-up and associated diseases. This allowed us to identify 9 patients with an urticarial eruption that was characterized histopathologically by a perivascular and interstitial neutrophilic infiltrate with intense leukocytoclasia but without vasculitis and without dermal edema. Four patients also had small foci of necrobiotic collagen bundles. The eruption consisted of pale, flat or only slightly raised, nonpruritic macules, papules, or plaques. Elementary lesions resolved within 24 hours. Purpura, angioedema, and facial swelling were not seen, but dermographism was present in 1 patient. Six patients had fever, 7 had polyarthritis, and 6 had leukocytosis. Seven patients had associated systemic diseases: adult-onset Still disease (3 patients), systemic lupus erythematosus (3 patients), and Schnitzler syndrome (1 patient).A similar rash has been reported previously in the literature, mostly in patients with systemic inflammatory diseases, but the majority of patients reported under the undefined designation of "neutrophilic urticaria" did have a different clinicopathologic presentation. Thus, we suggest naming this eruption "neutrophilic urticarial dermatosis," to emphasize that this entity expands the broad group of cutaneous manifestations of neutrophilic aseptic disease. This entity bears important medical significance as it is strongly indicative of an associated systemic disease, mainly Schnitzler syndrome, adult-onset Still disease, lupus erythematosus, and the hereditary autoinflammatory fever syndromes.

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.

Pulmonary necrobiotic nodules: a rare extraintestinal manifestation of Crohn's disease.

The present article reports the case of a 22-yr-old female with new onset Crohn's colitis, anterior uveitis and multiple pulmonary nodules which, on histological examination, were necrobiotic nodules. This is a rare but recognised pulmonary extraintestinal manifestation of Crohn's disease and only the fourth reported case. The present case report is followed by a brief review of the relevant literature.