Retrospective assessment of immunologic and histologic heterogeneity in granuloma annulare by cytokine staining.

BACKGROUND: Type 1 (Th1) and Type 2 (Th2) immunity have both been implicated in granuloma annulare (GA). To what extent these pathways contribute to clinical/histologic heterogeneity and/or distinct disease endotypes remains unexplored. METHODS: We retrospectively analyzed 30 GA biopsies with either palisaded or interstitial histology with and without eosinophils. We performed RNA in situ hybridization to assess how markers of Type 1 (interferon gamma), Type 2 (interleukin [IL]4, IL13, IL5), and Type 3 (IL17A) immunity in GA compared with canonical inflammatory disorders and whether markers correlated with histology. We analyzed another cohort of 14 patients who had multiple biopsies across anatomic space and time for individual conservation of histologic features. RESULTS: Interferon (IFN)G staining is highest in GA relative to other cytokines. Type 2 cytokine staining is less prominent, with IL4 increased in interstitial pattern cases. Eosinophils did not correlate with Type 2 markers. Patients with multiple biopsies display intrapatient variability in histology. CONCLUSION: Type 1 inflammation predominates over Type 2 inflammation in GA irrespective of histologic pattern. Distinct disease endotypes were not detected.

Sarcoidal Granuloma Annulare-Like Dermatitis and Vasculitis With Granulomatous Features: An Atypical Case of Giant Cell Arteritis.

ABSTRACT: Giant cell arteritis (GCA) is a diagnosis that clinicians should not miss because of the accompanying risk of irreversible vision loss. GCA can present without the classic symptoms of headache and temporal artery tenderness, which may lead to a delay in diagnosis. Cutaneous findings, although rare, have been associated with GCA. Accordingly, it is imperative to be aware of the broad clinical and histological presentations of GCA, including the cutaneous findings, because they may prove to be harbingers of impending disease. We present a unique case of GCA where 2 distinct cutaneous morphologies, sarcoidal granuloma annulare-like dermatitis and leukocytoclastic vasculitis with granulomatous features, presented simultaneously before the classic symptoms of headache and unilateral vision loss.

[Dermoscopy of granulomatous and autoimmune skin diseases]. / Dermatoskopie von granulomatösen und Autoimmunerkrankungen der Haut.

Dermoscopy is an easily accessible, noninvasive diagnostic tool, originally used in the differentiation of benign and malignant skin tumors. Other structures beside pigment content observed by dermoscopy, e.g., scaling, follicles, or vessels, may present in a specific pattern in different dermatoses. Recognition of these patterns may aid the diagnosis of inflammatory and infectious dermatological conditions. The aim of this article is to review the distinct dermoscopic features of granulomatous and autoimmune skin diseases. Diagnosis of granulomatous skin disorders is based on the histopathological examination. The dermoscopic picture of these diseases (cutaneous sarcoidosis, granuloma annulare, necrobiosis lipoidica, and granulomatous rosacea) show many similarities; however, there are some differences to note between the dermatoses, mainly in granuloma annulare. The cornerstones of the diagnostic process of autoimmune skin diseases (morphea, systemic sclerosis, dermatomyositis, cutaneous lupus erythematosus) include the clinical picture, immunoserology, and histology; however, dermoscopy may aid the diagnostic process and follow-up of the patients. For those diseases, where vascular abnormalities play an important role in the pathogenesis, videocapillaroscopy is used for examination of the microcirculation at the nailfold capillaries. Dermoscopy can be an easy-to-use everyday diagnostic tool in clinical practice regarding granulomatous and autoimmune skin diseases. Although punch biopsy is inevitable in many cases, the distinct dermoscopic structures can aid the diagnostic process.

Periocular Granuloma Annulare: A Case Report of a Rare Childhood Disease in an Adult.

A 21-year-old female presented to the oculoplastic clinic with a 2-year history of raised lesions in the right upper eyelid and lateral canthus area. Due to their unusual appearance, the patient underwent an excisional biopsy of the lateral canthus lesion. A diagnosis of granuloma annulare was made after histopathology demonstrated palisading epithelioid granulomas with central fibrinoid necrosis and Alician blue positive acid mucin. Granuloma annulare is a benign inflammatory skin condition characterized by firm discolored papules or nodules classically arranged in an annular pattern. Periocular involvement is extremely rare in adults and may pose a diagnostic challenge to ophthalmologists unfamiliar with its presentation and management.

Generalized perforating granuloma annulare associated with latent tuberculosis successfully treated with isoniazid: case report and review.

Generalized perforating granuloma annulare (GPGA) is a very rare form of granuloma annulare, with only 31 reported cases to the best of our knowledge. Furthermore, GPGA is a chronic disease that mimics many diseases, with no known exact etiology, resulting in a lack of specific clinical criteria leading to a lack of guidelines for diagnosis and therapy. In GPGA, papules are the predominant lesions followed by central crusting/scaling or umbilication; pustules, plaques, annular lesions or nodules are less frequent. We report a 66-year-old woman who presented with a 7-month history of mostly asymptomatic generalized infiltrated, flesh-colored to red-brown umbilicated or crusted papules. Histopathological findings were compatible with perforating granuloma annulare. Diagnostic workup revealed latent tuberculosis. To the best of our knowledge, this is the second published case of GPGA associated with latent tuberculosis and the first one that was successfully treated by isoniazid monotherapy. From our case we can speculate and support the theory that GPGA is a phenotypic granulomatous response to multiple etiologies and/or antigenic stimulation and that testing for tuberculosis should be seriously considered in the evaluation of patients with GPGA.

The Clinical Presentation and Comorbidities Associated with Granuloma Annulare in the Pediatric Population: A Retrospective Study.

Granuloma annulare (GA) is a cutaneous inflammatory disorder of unknown cause, typically characterized by an annular arrangement of dermal papules and nodules. While GA in adults has been linked to diabetes mellitus (DM) and other conditions, these associations have been less studied in children. A retrospective chart review was conducted of all pediatric patients diagnosed with GA at an urban academic institution over a 7-year period. A total of 47 patients were reviewed. Of these, 41 (85.1%) patients had localized GA, 3 (6.38%) had subcutaneous GA, 2 (4.26%) had generalized GA, and 1 (2.13%) had both localized and subcutaneous GA. The extremities were the most common site of involvement across all morphologies. Atopic conditions were determined in 23 (48.9%) patients, 16 (34.0%) of which had asthma, either alone or in conjunction with atopic dermatitis or allergic rhinitis. None of the patients carried a diagnosis of DM, and all 11 patients who were tested within 3 years of the documented visit had normal results. In summary, this retrospective series characterizes the presentation of pediatric GA and highlights a potential association with atopy. An association with DM was not observed.