Formation of palisading granulomas in a patient with chronic cutaneous cryptococcosis

We describe a unique case of a 57-year-old man who developed a chronic cryptococcal infection with cutaneous lesions that showed palisading granulomas. To our knowledge, this is the first report of this entity in the skin. We also discuss the differential diagnosis of palisading granulomas.     

Immunohistochemical features of cutaneous granulomas in primary immunodeficiency disorders: a comparison with cutaneous sarcoidosis

Background:  Cutaneous granulomas can occur in patients with a primary immunodeficiency disorder. In some cases, an infectious cause cannot be revealed. The pathogenesis of these granulomas still remains to be elucidated. The aim of this study was to study differences or overlap between these rare granulomas and sarcoidosis-related granulomas.
Methods:  Markers for T-cell subsets (CD3, CD4, CD8 and CD45RO), Langerhans' cells (CD1a), macrophages (CD68), B cells (CD20) and NK cells (CD56) were stained immunohistochemically. The amount of CD4+ and CD8+ cells in the granulomas was counted. Results were compared with the CD4+/CD8+ ratio in peripheral blood.
Results:  In the granulomas of two of three patients with a primary immunodeficiency disorder, the cytotoxic T cells (CD8+) outnumbered the T-helper cells (CD4+) with a counted CD4+/CD8+ ratio <<1. In contrast, the granulomas in the cutaneous sarcoidosis patients showed a predominance of CD4+ cells, with CD4+/CD8+ ratios >2.
Conclusions:  A lower CD4+/CD8+ ratio was found in the cutaneous granulomas of patients with a primary immunodeficiency disorder (unclassified combined immunodeficiency, autoimmune lymphoproliferative syndrome and ataxia teleangiectasia) as compared with the patients with cutaneous sarcoidosis. The possible implications of these findings are discussed in this paper.     

CIAS1 mutation in a patient with overlap between Muckle-Wells and chronic infantile neurological cutaneous and articular syndromes

The Muckle-Wells syndrome is a rare autosomal dominant disorder belonging to the group of hereditary fever syndromes. The chronic infantile neurological cutaneous and articular (CINCA) syndrome is a systemic inflammatory disorder of unknown etiology with neonatal onset. They are considered as two different entities. We report the case of a 36-year-old man suffering since birth from a nonpruritic generalized urticaria, with inflammatory flares, joint manifestations and progressive deafness requiring a bilateral hearing aid. An initial diagnosis of Muckle-Wells syndrome was made. However, the patient had an unusual clinical presentation with slightly dysmorphic facial appearance, clubbing of the fingers, mild mental retardation and papilledema. After a genetic advice, a diagnosis of CINCA syndrome was made. Search for mutations in the CIAS1 gene revealed a new mutation in a heterozygous state. This case report really raises the question of a link between these two inflammatory diseases. Further studies are needed to confirm the involvement of mutations of the CIAS1 gene in CINCA syndrome.     

Cutaneous sarcoidal granulomas in a patient with primary biliary cirrhosis.

We report here the case of a fifty-year-old Japanese woman with a history of primary biliary cirrhosis who presented with a sarcoidal granulomatous plaque on the face. Although the occurrence of extra-hepatic granulomas and primary biliary cirrhosis has been documented, this is the first case report of cutaneous sarcoidal granulomas in the absence of demonstrable sarcoidosis occurring in a patient with primary biliary cirrhosis. Because primary biliary cirrhosis and sarcoidosis are systemic granulomatous diseases of unknown cause, the coexistence of findings compatible with both entities has led to speculation that they are related. We provide a brief review of these two diseases to help examine this hypothesis.     

Exacerbation of skin lesions during fever in a patient with chronic infantile neurologic cutaneous articular (CINCA) syndrome

Chronic infantile neurologic cutaneous articular (CINCA) syndrome is a serious chronic systemic inflammatory disease that presents at a young age and that is characterized by skin, joint, and central nervous system disease. Skin symptoms are the first to appear, in the form of a longstanding nonpruritic urticarial rash, with exacerbations coinciding with episodes of fever, arthritis, and enlarged lymph nodes. The findings of biopsy of skin lesions are extremely variable but characterized by perivascular neutrophilic infiltrate. With the discovery of mutations in the CIAS1 gene, which encodes a protein known as cryopyrin, this entity has been classified as one of the cryopyrin-associated autoinflammatory diseases, along with familial cold urticaria and Muckle-Wells syndrome. This discovery has also made available new therapeutic options. We present the case of a boy diagnosed with CINCA syndrome who presented with an outbreak of painful skin lesions and fever. These lesions were thought to be an exacerbation of underlying lesions during an episode of fever.     

Etanercept-induced cutaneous and pulmonary sarcoid-like granulomas resolving with adalimumab

A 59-year-old female with rheumatoid arthritis on etanercept therapy presented with a 7-cm-large subcutaneous forearm mass. Multiple smaller nodules subsequently developed on the upper and lower extremities. Except for a new cough, the patient was systemically well. Biopsy of the mass showed sarcoidal type granulomatous inflammation with nodular aggregations of non-necrotizing epithelioid histiocytes in the subcutis. A chest computed tomography (CT) scan showed mediastinal adenopathy consistent with pulmonary sarcoidosis. Etanercept was discontinued, and the patient was started on adalimumab for rheumatoid arthritis control. The cutaneous nodules fully resolved in 6 months with no additional treatment. A 4-month follow-up CT scan showed significant regression of mediastinal adenopathy. The patient has since been maintained on adalimumab therapy for 2 years with no recurrence of sarcoid-like manifestations. Biologic response modifiers targeting tumor necrosis factor alpha (TNFα) are effective treatments of chronic inflammatory conditions such as rheumatoid arthritis and psoriasis. TNFα represents a major cytokine in granuloma formation, and TNFα inhibitors are sometimes efficacious in the treatment of sarcoidosis. Paradoxically, there is a small volume of literature implicating TNFα inhibitors in the development of sarcoid-like disease. We present this case to promote the recognition of TNFα inhibitor-induced sarcoidosis and to illustrate the wide clinicopathologic differential of sarcoidal type granulomas.     

Humoral response in a patient with cutaneous nocardiosis

The clinical appearance of infection due to Nocardia spp. varies widely. The low sensitivity of direct microscopy and the slow growth of the organism challenge the laboratory diagnosis. We present the case of a skin abscess in an immunocompetent man caused by Nocardia brasiliensis. Diagnosis was made by cultivation and 16S rRNA sequencing. Using indirect immunofluorescence and Western blot, a strong antibody response to the N. brasiliensis isolate could be demonstrated. Serological tests might therefore be useful for the diagnosis and management of nocardial infections. Copyright (R) 2000 S.Karger AG, Basel     

Serum angiotensin I-converting enzyme level in patients with cutaneous sarcoidal granulomas

In a previous study we found that only half of those patients presenting with cutaneous sarcoidal granulomas have evidence of systemic involvement. The current study was designed to determine whether abnormal angiotensin-converting enzyme (ACE) levels were predictive of multisystem disease. Serum ACE levels were determined in 15 patients with active cutaneous sarcoidal granulomas. The ACE levels were elevated in ten of the patients but did clearly differentiate those with systemic involvement. Three of the six patients with disease localized to the skin had elevated ACE levels, whereas seven of the nine patients with systemic disease had elevated ACE levels. The ACE levels did not correlate with the extent of cutaneous disease, or any individual or combined system involvement. A normal ACE level cannot be used to rule out a diagnosis of sarcoidosis and, conversely, an abnormal level does not confirm multisystem involvement.     

Caseating Cutaneous Granulomas in a Child with Common Variable Immunodeficiency

Abstract: Cutaneous, noninfectious, granulomatous lesions have been reported occasionally In different types of Immunodeficiencies, Including common variable immunodeficiency (CVID). We present a child with CVID and cutaneous granulomas with a strikingly prominent caseating necrosis. We think that such granulomatous lesions constitute a distinctive manifestation of Immunodeficiency, and may reflect an altered immune response. Corticosteroids have been of benefit to our patient, as well as in similar cases.     

Dermatomyositis-like syndrome in X-linked hypogammaglobulinemia. Case-report and review of the literature

A case of dermatomyositis-like syndrome is described in a 19-year-old man with a history of Bruton's hypogammaglobulinemia. Although the patient had central-nervous-system manifestations (seizures), no echovirus was isolated in the cerebrospinal fluid, in contrast to previously reported cases. Data for our case and the 15 cases previously reported in the literature are reviewed. HLA typing of our patient revealed the presence of HLA B8 and DR3, which seems to play a major role in juvenile dermatomyositis.