Giant Cell Arteritis with Generalized Granuloma Annulare.

We report the case of an 80-year-old man with generalized granuloma annulare (GGA) who subsequently developed giant cell arteritis (GCA). Steroid treatment was effective for both diseases in this case. Although cases of concomitant GGA and GCA have rarely been reported, previous studies suggest that common histological characteristics underlie the two diseases. It is therefore necessary to recognize that GGA can be complicated by GCA, particularly when typical symptoms, such as headache and visual disturbance, are present.

Skin manifestations in course of celiac disease: case report and review of the literature.

Skin and gut represent physical and immunological barriers between internal and external environment. Some affections involving the intestine, such as celiac disease, are reported to be associated with several different cutaneous diseases, like dermatitis herpetiforme or psoriasis. This could be better explained if gut and skin are taken as complex structures that share physio-pathological and immunological aspects. As a proof, we present the case of a woman affected by celiac disease who presented with three different skin manifestations strongly related in terms of onset, response to therapy and improvement during gluten-free diet.

Granuloma anular: estudio inmunohistoquímico para células de Langerhans S-100 y dendríticas interdigitantes dérmicas fascina+: parte 1 / Annular granuloma: inmunohistoquímico study for cells of Langerhans S-100 and dendritic skin interdigitantes fascina+: part 1

El granuloma anular es un síndrome cutáneo bien definido, con una multiplicidad de manifestaciones clínicas y diversas imágenes histopatológicas. Su patogenia en relación a diversos antígenos incluye mecanismos inflamatorios inmunes como respuesta de hipersensibilidad retardada mediada por linfocitos T, que se expresan como una reacción inflamatoria linfohistiocítica, granulomatosa y necrobiótica. Se estudian 6 casos con diversas formas clínicas de granuloma anular: 4 localizadas y 2 generalizadas, con distintas imágenes histopatológicas. No se constatan enfermedades sistémicas y los exámenes de laboratorio son normales. Se realizaron técnicas de inmunohistoquímica para células de Langerhans S-100+ y células dendríticas interdigitantes dérmicas Fascina+. Estos granulomas anulares muestran la presencia de ambas células en todos los casos con variable intensidad, con activación de las células de Langerhans en epidermis y dermis y de las células interdigitantes dérmicas Fascina+ en la dermis reticular. Ambas células son presentadoras de antígenos con activación final de toda la vía eferente linfocitos T. La activación de las células de Langerhans sugiere la posibilidad de que factores antigénicos exógenos podrían estar presentes en la respuesta inflamatoria inmune específica.

Granuloma anular: estudio inmunohistoquímico para dendrocitos factor X111a+, macrófagos CD68+, linfocitos T CD4+, CD8+ CDRO45+ y linfocitos B CD20+ Parte 2 / Annular granuloma: inmunohistoquímico study for dendrocitos X111a+ factor, macrophages CD68+, lymphocytes T CD4+, CD8+ CDRO45+ and lymphocytes B CD20+ Part 2

El granuloma anular es un proceso inflamatorio crónico granulomatoso con distintas manifestaciones clínicas e imágenes histopatológicas con etiología aún desconocida. En esta segunda parte del trabajo sobre el granuloma anular se analizan los mismos 6 pacientes adultos descritos en la Parte 1. Se estudian con técnicas de inmunohistoquímica con anticuerpos monoclonales para dendrocitos dérmicos tipo l FX111a+, macrófagos CD68+, linfocitos T y B. Se evaluaron en forma cualitativa la cantidad de células marcadas en relación a los controles. Los resultados muestran:1) intensa positividad de los dendrocitos dérmicos tipo l FXllla+, que son células presentadoras antígenos y activan otras células produciendo liberación de citoquinas y factores pro-inflamatorios; 2) intensa actividad de los macrófagos CD68+ colaborando en la capacitación de antígenos y transmitiendo la información a otras células, y 3) presencia de linfocitos T CD4+, CD8+, CDRO45+ memoria y negativos para linfocitos B CD20+. En la patogenia del granuloma anular estas células, conjuntamente con las células del linaje de células de Langerhans y células dendríticas dérmicas Fascina+, determinan la captación de antígenos y provocan la activación de la cadena eferente linfocitos T que termina en la inflamación granulomatosa. Nuestros hallazgos en los dos trabajos muestran que en el granuloma anular se encuentran múltiples células presentadoras de antígenos provocando una respuesta inmune de hipersensibilidad retardada mediada por linfocitos T.

Granuloma anular elastolítico de células gigantes: a propósito de 2 casos / Annular elastolytic giant cell granuloma: apropos of 2 cases

El granuloma naular elastolítico de células gigantes (GAECG) es una dermatosis granulomatosa benigna, poco frecuente, crónica y de etiología desconocida, localizada en áreas fotoexpuestas. La histopatología demuestra la presencia de células gigantes con elastólisis y elastofagocitosis. Describimos dos casos de GAECG y se realiza un revisión de esta patología, diagnósticos diferenciales y posibilidades terapéuticas.

Granuloma actínico. Estudio clínico e histológico de cinco casos / Actinic granuloma. Clinical and histological study of five cases

Se presentan 5 pacientes con lesiones anulares en la cara y el cuello que fueron estudiados desde un punto de vista clínico e histológico, y que diagnosticamos de granuloma actínico de O'Brien. Además, hemos revisado la literatura médica reciente analizando la patogenia de esta entidad y el papel de la exposición solar como factor desencadenante. Hacemos mención especial a la controversia que suscita el granuloma actínico como una entidad específica y las diferencias histológicas con el granuloma anular en zonas de piel fotoexpuestas (AU)

Expression of IFNgamma, coexpression of TNFalpha and matrix metalloproteinases and apoptosis of T lymphocytes and macrophages in granuloma annulare.

Granuloma annulare, a prototype noninfectious granulomatous dermatitis, is morphologically characterized by a necrobiotic core surrounded by a cellular infiltrate. Because of many morphological similarities to tuberculosis, granuloma annulare has been suggested to represent a delayed-type hypersensitivity (Th1) reaction in the course of which inflammatory cells elicit matrix degradation. In the present study we (1) investigated the expression of interferon-gamma as the most important Th1-associated cytokine, (2) sought in situ evidence for the coexpression of the proinflammatory cytokine tumor necrosis factor-alpha and cytokine-regulated matrix metalloproteinases 2 (gelatinase A) and 9 (gelatinase B), and (3) sought to determine whether shrunken cells seen within necrobiotic areas of granuloma annulare are apoptotic cells. In situ hybridization combined with immunofluorescence showed that large numbers of infiltrating CD3+ lymphocytes express interferon-gamma. Application of catalyzed signal amplification in immunodetection revealed that the vast majority of CD3+ lymphocytes and CD68+ macrophages contained tumor necrosis factor-alpha. Immunohistochemistry demonstrated that macrophages producing tumor necrosis factor-alpha coexpress matrix metalloproteinases 2 and 9. In situ end-labeling combined with immunofluorescence detected few apoptotic T cells in perivascular regions and numerous apoptotic macrophages within necrobiotic areas. These results suggest that in granuloma annulare interferon-gamma+ Th-1 lymphocytes may cause a delayed-type hypersensitivity reaction whereby macrophages are differentiated to aggressive effector cells expressing tumor necrosis factor-alpha and matrix metalloproteinases. In parallel, activation-induced apoptosis in lymphocytes and macrophages may serve to restrict the destructive potential of the inflammatory cells.

Granuloma anular asociado al HIV / Granuloma annulare associate to HIV

Se presentan seis casos de granuloma anular (GA) en pacientes HIV positivos. Tres pacientes eran de sexo masculino y tres de sexo femenino. Los seis pacientes presentaban pequeñas pápulas diseminadas que involucionaron en corto tiempo y precedieron a un notable deterioro de su estado general. La histopatología fue vinculable a GA. El GA es una dermatosis inflamatoria benigna cuya etiología es desconocida. En pacientes HIV positivos se ha informado que particulas virales de HIV circulantes serían un factor precipitante del GA. La alteración de los CD4 y CD8 podría ser responsable del curso de esta patología (AU)

Granuloma anular asociado al HIV / Granuloma annulare associate to HIV

Se presentan seis casos de granuloma anular (GA) en pacientes HIV positivos. Tres pacientes eran de sexo masculino y tres de sexo femenino. Los seis pacientes presentaban pequeñas pápulas diseminadas que involucionaron en corto tiempo y precedieron a un notable deterioro de su estado general. La histopatología fue vinculable a GA. El GA es una dermatosis inflamatoria benigna cuya etiología es desconocida. En pacientes HIV positivos se ha informado que particulas virales de HIV circulantes serían un factor precipitante del GA. La alteración de los CD4 y CD8 podría ser responsable del curso de esta patología

Systemic scleroderma and perforating granuloma annulare: differential diagnosis from calcinosis.

BACKGROUND: Systemic scleroderma is a disorder of unknown etiology with skin sclerosis. Its major histological features are swollen and homogenized collagen bundles. OBJECTIVE AND METHODS: We describe 2 patients with systemic sclerosis who have multiple umbilicated nodules indistinguishable from calcinosis cutis. RESULTS: Histological examinations including Von Kossa staining revealed features of perforating granuloma annulare, but not of calcinosis cutis. CONCLUSION: The association may not be fortuitous but both diseases may be etiologically related.

Precipitating factors and associated diseases in 84 patients with granuloma annulare: a retrospective study.

In a retrospective study including 84 patients, we assessed precipitating factors of granuloma annulare (GA) and associated pathologies. Fifteen per-cent of the patients reported stress as an important trigger of GA, and in 10 patients (12%) we found an association between GA and diabetes mellitus: 3 latent, 4 type I and 3 type II. Eight of the diabetic patients presented multiple and 5 generalized GA. They suffered significantly more often from chronic relapsing GA than nondiabetic patients.

Granuloma annulare and necrobiosis lipoidica tissue reactions as a manifestation of systemic disease.

Granuloma annulare (GA) and necrobiosis lipoidica (NL) are generally considered to be idiopathic cutaneous palisading granulomatous dermatitides. There are sporadic reports of such lesions occurring in patients with coexistent systemic diseases other than diabetes mellitus. Having encountered 49 patients whose skin biopsies showed GA or NL lesions in the setting of extracutaneous disease, the authors set out to assess their clinical and histopathological findings to determine if any parameters were predictive of underlying systemic disease. Fifty-two skin biopsies from 49 patients having either GA or NL in whom there was a clinical history of an associated systemic disease were analyzed by light microscopy. The main systemic disease associations were rheumatologic, endocrine, hematologic, infectious, and inflammatory bowel diseases, ANCA positive vasculitic syndromes, and sarcoidosis. The clinical and histomorphological features were compared with those of a control group of patients whose skin biopsies showed GA or NL and in whom there was no history of extracutaneous disease. For the systemic disease group, patients were selected either retrospectively or prospectively from 160,000 cases accessioned in a 24-month period in the dermatopathology databases of Pathology Services, Inc (Cambridge, MA) and Central Medical Laboratories (Winnipeg, Canada). All systemic disease cases from the former service were analyzed blindly by the second author and from the latter service were analyzed blindly by the first author. Patients in the control group were obtained retrospectively from the Pathology Services Inc. database by the authors. The location of the lesions was atypical in 30 of 34 biopsies from systemic disease patients with a GA tissue reaction versus 10 of 22 biopsies of GA in the control group (P = .001). Six of 18 biopsies from patients with NL tissue reactions in the systemic disease group showed an atypical location, versus only 1 of 9 biopsies of NL from the control group (P = .19). The clinical diagnostic considerations were much broader in the systemic disease group versus the control group and included vasculitis, panniculitis, and connective tissue diseases including morphea in the former. In 22 of 34 GA biopsies and 16 of 18 NL biopsies from the systemic disease group, an active vasculopathy of leukocytoclastic, granulomatous, or thrombogenic subtypes was demonstrable. None of the GA or NL biopsies from the control group showed a similar active vasculopathy. An active vasculopathy was predictive of systemic disease in patients having either a GA-like or an NL-like tissue reaction (P < .001). Fifteen of 34 GA and 7 of 18 NL biopsies in the systemic diseases group showed extravascular neutrophilia in contrast to 3 of 22 GA (P = .02) biopsies and 2 of 9 NL (P = .33) biopsies in the control group. The finding of an active vasculopathy in a skin biopsy specimen showing a GA- or NL-like tissue reaction, particularly in the setting of an atypical clinical presentation both with respect to the location and appearance of lesions, should prompt consideration of an underlying systemic disease, as should extravascular neutrophilia in a skin biopsy showing a GA-like tissue reaction.

[Localized granuloma annulare in children: outcome in 30 cases]. / Granulome annulaire localisé chez l'enfant: évolution de 30 cas.

BACKGROUND: The outcome of granuloma annulare in childhood is not well defined. POPULATION AND METHODS: A questionnaire was sent to the family of 40 children under 15 years of age examined for granuloma annulare from 1987 to 1992. Thirty of them answered, permitting a retrospective study. RESULTS: The sex-ratio F:M was 1.3:1. Ages ranged from 1 to 13 years (mean: 4.5 years). Lesions developed before the age of 5 years in 76.7% of cases. Involved sites were essentially the back of hands and feet; lesions were unique in half of the cases. No association with diabetes mellitus was found. Three familial cases were observed. Duration of lesions varied from 6 months to 7 years (mean: 2.5 years). Age at onset, sex, biopsy and treatment had no influence on outcome. CONCLUSION: Granuloma annulare in children is a benign disorder but its course may last up to several years.

Treatment of granuloma annulare with tranilast.

Three cases of granuloma annulare which did not exhibit a self-limited course were treated with tranilast at the dose of 300 mg/daily. The treatment resulted in the resolution of skin lesions within three months of administration. Although spontaneous resolution is often observed in granuloma annulare, tranilast may provide an alternative therapy for the treatment of cases resistant to spontaneous healing.