Reactive Granulomatous Dermatitis Research Articles

Reactive Granulomatous Dermatitis: A Descriptive Study of 10 Patients.

Reactive granulomatous dermatitis (RGD) is a rare and misunderstood skin disorder. It includes interstitial granulomatous dermatitis and palisaded neutrophilic and granulomatous dermatitis: 2 entities of the same spectrum. Multiple associations are described with RGD in the literature, including autoimmune diseases, malignancy, and drugs. To report and describe the suspected associations with RGD at the time of diagnosis and in the following year. We retrieved and described cases of RGD confirmed by skin biopsy and clinicopathologic correlation. All patients were evaluated in the Centre Hospitalier Universitaire de Québec-Université Laval between January 2000 and December 2020. Collected data include the systemic diseases (autoimmune disease, malignancy) and suspected drugs, in addition to the clinical presentation and prescribed treatments. Out of the 10 patients with RGD, 7 patients were known to have an autoimmune disease at the time of diagnosis. They either had inflammatory arthritis (3/10) or inflammatory bowel disease (4/10). There was a clinical suspicion of a possible association with a tumor necrosis factor (TNF) inhibitor in 2 of these 7 patients. Among the 3 patients with idiopathic RGD at the time of diagnosis, 1 patient developed a high-grade B-cell lymphoma 6 months later. There was no new association identified in the following year for patients with a known autoimmune condition. This descriptive study supports RGD and its previously described systemic associations, particularly autoimmune diseases, malignancy, and certain drugs (specifically TNF inhibitors). The majority of patients already had one of these associations identified at the time of histopathological diagnosis.

Interstitial Granulomatous Dermatitis and Palisaded Neutrophilic Granulomatous Dermatitis: Retrospective Clinicopathological Analysis of 16 Cases.

Reactive granulomatous dermatitis (RGD) is a new entity, which is highly associated with systemic disorders. There is scarce data regarding interstitial granulomatous dermatitis (IGD) and palisaded neutrophilic granulomatous dermatitis (PNGD). We aimed to evaluate clinical and histopathological characteristics of IGD and PNGD as unified entities under the term of RGD. Observational, retrospective, single-center study of patients diagnosed with IGD and PNGD between 2012 and 2021 were included in the study. Of 16 patients (14 females and 2 males) with RGD, 13 had IGD and 3 had PNGD with a mean age of 62.5 years. The most common clinical presentation was plaques 37.5% (N=6), followed by patches 25% (N=4). The most common localization of involvement was lower extremity 75% (N=12), followed by trunk and upper extremity. Multiple localization of involvement was determined in 75% (N=12) of patients. None of the patients had rope sign. Associated comorbidities such as autoimmune diseases and malignancies were detected in 68.7% (N=11) of patients. In majority of biopsies (87.5%; N=14), there were lymphohistiocytic cell infiltration. Other accompanying cells were scarce neutrophils 31.2% (N=5) and eosinophils 31.2% (N=5). All of the biopsies had interstitially located lymphohistiocytic cell infiltration surrounding with swollen and degenerated collagen. Palisaded pattern was determined in 18.7% (N=3) of patients and floating sign was seen in 18.7% (N=3) of biopsies. RGD is a rare entity and most patients with RGD had associated disorders such as autoimmunity or malignancy. There is overlapping between IGD and PNGD, therefore supporting the usage of umbrella term as reactive granulomatous dermatitis is compatible with the literature.

Underlying Systemic Diseases in Interstitial Granulomatous Dermatitis and Palisaded Neutrophilic Granulomatous Dermatitis: A Systematic Review

Background: Interstitial granulomatous dermatitis (IGD) and palisaded neutrophilic granulomatous dermatitis (PNGD) are uncommon presentations of reactive granulomatous dermatitis. Histologic lesions characterized by IGD/PNGD patterns have been associated with systemic diseases, causing an unmet need for revealing clinical correlates. Objective: The aim of this study was to unravel the systemic diseases beyond dermatitis of IGD/PNGD. Methods: This study analyzed data from case studies, case series, and retrospective cohorts by searching PubMed, Embase, Web of Science, and the Cochrane Library, with no start date or language restrictions on Sep 4, 2021. Results: One hundred ninety-six publications were included (458 cases in total, 216 with details). Systemic diseases associated with IGD/PNGD were classified into 5 groups. Autoimmune disorders (n = 103, 47.6%) including rheumatoid arthritis (n = 51, 23.6%), systemic lupus erythematosus (n = 20, 9.3%), and others were the most common across all underlying diseases, followed by drug eruption (n = 52, 24.1%) such as tumor necrotic factor inhibitor reaction (n = 18, 8.3%) and malignancies (n = 27, 12.5%) such as hematologic malignancy (n = 20, 9.3%). The rest were infectious diseases (n = 12, 5.6%) and accidental conditions (n = 3, 1.4%). Conclusion: IGD/PNGD might be associated with autoimmune disorders, drug eruption, malignancies, infectious diseases, and accidental conditions. Patients with IGD/PNGD need further follow-up.

Reactive granulomatous dermatitis as a clinically relevant and unifying term: a retrospective review of clinical features, associated systemic diseases, histopathology and treatment for a series of 65 patients at Mayo Clinic.

Reactive granulomatous dermatitis (RGD) is an umbrella term used to describe interstitial granulomatous dermatitis (IGD), palisaded neutrophilic and granulomatous dermatitis (PNGD), and interstitial granulomatous drug eruption (IGDR). The aim of this study was to describe systemic associations of RGD, explore possible associations between histopathologic findings and systemic RGD associations and determine clinical relevance of RGD subtypes. We retrospectively studied clinical and histopathologic characteristics of patients with RGD from 1990 through 2020. Of 65 patients with RGD (41 women, 24 men; median age at diagnosis, 62 years), 37 had IGD, 26 had PNGD, and 2 had IGDR. Fifty patients (76.9%) had an associated systemic condition; rheumatologic conditions were identified for 34 (52.3%) patients. The associated systemic condition occurred before RGD in approximately 75% of patients. Statistical analyses did not show significant associations between specific subtypes of RGD and systemic diseases or treatment response, and specific histopathologic findings were not predictive of an associated systemic disease. Although most patients with RGD had an associated systemic condition, subtypes of RGD did not correlate with systemic associations, lending support to the use of the umbrella term RGD.

Reactive granulomatous dermatitis: A useful and encompassing term

Reactive granulomatous dermatitis: A useful and encompassing term

Reactive granulomatous dermatitis associated with ovarian cancer and a review of its role as a harbinger for malignancy.

Reactive granulomatous dermatitis (RGD) is a rare dermatosis with a variety of cutaneous manifestations unified by a dermal granulomatous infiltrate on histology. Rheumatoid arthritis and autoimmune disease are classic associations, but an increasing number of cases have been attributed to covert malignancy. Only 41 cases of paraneoplastic RGD have been documented to our knowledge and we present an additional case that manifested eight months prior to the diagnosis of ovarian cancer and clinically mimicked morphea. Histopathologic examination identifying palisaded CD68+ cells and collagen degeneration are helpful in diagnosing this entity which may mimic a host of other cutaneous processes, including metastatic disease. Cancer-directed therapies have been successful in clearing paraneoplastic RGD with or without the addition of corticosteroids, as RGD severity may be driven by the underlying malignancy. This case highlights the importance of utilizing histopathology to confirm the diagnosis given its nonspecific clinical findings, as well as the importance of considering malignancy and metastatic disease in patients diagnosed with RGD regardless of their cancer history.

Reactive granulomatous dermatitis as a histological pattern including manifestations of interstitial granulomatous dermatitis and palisaded neutrophilic and granulomatous dermatitis: a study of 52 patients

Confusion exists regarding interstitial granulomatous dermatitis (IGD) and palisaded neutrophilic and granulomatous dermatitis (PNGD). To determine whether IGD and PNGD are two different entities, or whether they must be considered as two subtypes of the same reactive pattern, and thus whether the unification of the nomenclature is necessary. Observational retrospective multicentre study of patients with IGD and PNGD evaluated between 1999 and 2019 and review of their clinical and histological features. We identified 52 patients (38 women and 14 men). Clinical and histological findings of IGD were observed in 88.4% of cases. The most common cutaneous lesions were plaques/macules (IGD) or annular plaques and papules/nodules (PNGD), located mostly on the limbs and trunk. The rope sign was developed in two patients with IGD that associated autoimmune disorders. Similar associated comorbidities (75%) were found in both entities, mainly autoimmune diseases (53.8%). In IGD, the infiltrate was predominantly lympho-histiocytic. Neutrophilic infiltrates, karyorrhexis and skin lesions with limited clinical course were mainly associated with PNGD biopsies. In biopsies with a limited recurrent course, a predominant lymphocytic inflammatory infiltrate was found. Collagen degeneration was present in 75.9% of cases. The floating sign was observed only in IGD type patients (63%). Overlapping histological findings were found in one fourth of cases, especially between IGD and interstitial granuloma annulare. Interface dermatitis, apparently unrelated to drug intake, was observed in 4 cases of IGD. We support the term reactive granulomatous dermatitis to unify both the clinical and histological findings of IGD and PNGD, and the overlapping between IGD and interstitial granuloma annulare. According to this, a spectrum of histological changes will be found depending on the clinical course of the skin lesions.

Granulomatous Dermatitis and Systemic Disease: An Association to Consider.

Granuloma annulare (GA) and interstitial granulomatous dermatitis (IGD) are granulomatous dermatoses with variable clinical appearances. GA is associated with diabetes mellitus, metabolic syndrome, chronic infections, and malignancies, while two Japanese reports described unusual cases of interstitial-type GA in setting of Sjogren syndrome. IGD was associated with rheumatoid arthritis, systemic lupus erythematosus, and autoantibodies. We report a case series of six patients with GA or IGD. Half of the patients were diagnosed with Sjogren syndrome, while all of them presented ANA positivity and the majority reported arthralgia. In many cases, GA showed interstitial-type histology, arising challenges in differential diagnosis with IGD. The overlap of clinical and histological features of GA and IGD can be explained considering them as a broad disease spectrum, including also the other forms of reactive granulomatous dermatitis. These conditions should be considered as an indicator of possible systemic disorders or other immunological dyscrasias, for which patients must be screened. Sjogren syndrome may be associated to GA also in Caucasians.

Clinical and histologic presentation of pediatric reactive granulomatous dermatitis.

To characterize the clinical and histologic presentation of reactive granulomatous dermatitis (RGD) in the pediatric population. In this multicenter retrospective chart review, 7 pediatric patients with biopsy-proven RGD were identified. Photographs, histology reports, and clinical course were reviewed to discover patterns in demographics, comorbid conditions, autoimmune sequelae, drug exposures, infections, morphology, and histologic features. Overall, 7 patients were included and analyzed. Most were female and Hispanic. All presented with a similar dermatologic phenotype previously described in the adult literature including macular erythema and annular, pink to violaceous, edematous papules and plaques, often involving proximal extremities and extensor joints. All biopsies demonstrated variable collagen alteration and a perivascular interstitial infiltrate of histiocytes with or without mucin. Neutrophils or karyorrhexic debris were present in 4/7 of the biopsies, and eosinophils were occasionally seen (2/7 cases). In all cases, RGD was associated with active SLE or led to a new diagnosis, and initiation of systemic treatment improved cutaneous disease. Pediatric RGD was more common in female patients and ethnic minorities, and strongly associated with SLE. Clinical and histologic presentations were consistent across all cases with only minor variations, suggesting that recognition and confirmation might be expedited by familiarity with these dominant patterns. Diagnosis of RGD in pediatric patients should prompt screening for SLE.

Granulomatous drug reactions from targeted therapeutics

Granulomatous drug reactions have been associated with many medications, including targeted therapeutics such as biologics and small molecule inhibitors. The four main clinicopathologic reaction patterns are drug-induced sarcoidosis-like reaction, reactive granulomatous dermatitis, granuloma annulare, and accelerated rheumatoid nodulosis. These reactions often develop months after exposure to the causative medication and clinically can mimic other granulomatous diseases or metastatic cancer, which may be differentiated with biopsy, tissue culture, and radiographic imaging. Granulomatous inflammation may be limited to the skin, where early recognition helps to facilitate diagnosis. Cutaneous manifestations vary by reaction pattern, ranging from erythema nodosum-like lesions to painful rheumatoid nodules to annular indurated plaques. Systemic granulomatous inflammation is typically only observed in sarcoidosis-like reaction or accelerated rheumatoid nodulosis and most often involves the lungs or lymph nodes. Targeted therapeutics implicated in granulomatous drug reactions are TNFα inhibitors, BRAF and MEK inhibitors, immune checkpoint inhibitors and, to a lesser extent, other cytokine modulators. TNFα inhibitors, in particular, are among the most common drugs in any class associated with the four primary granulomatous drug eruptions. We review the current literature on granulomatous reactions to these agents, including proposed mechanisms and the range of clinical manifestations. Management may include drug discontinuation, topical therapy, or systemic immunosuppression depending on the severity of the granulomatous drug reaction. In the setting of malignancy, granulomatous inflammation does not appear to be of prognostic value, although more studies are needed.

Reactive granulomatous dermatitis in association with topiramate ingestion

Reactive granulomatous dermatitis in association with topiramate ingestion

Reactive Granulomatous Dermatitis during Anti-TNF Therapy: A Case Report and Review of the Literature

Reactive Granulomatous Dermatitis during Anti-TNF Therapy: A Case Report and Review of the Literature

Reactive Granulomatous Dermatitis: A Review of Palisaded Neutrophilic and Granulomatous Dermatitis, Interstitial Granulomatous Dermatitis, Interstitial Granulomatous Drug Reaction, and a Proposed Reclassification.

The terms "palisaded neutrophilic and granulomatous dermatitis," "interstitial granulomatous dermatitis," and the subset "interstitial granulomatous drug reaction" are a source of confusion. There exists substantial overlap among the entities with few strict distinguishing features. We review the literature and highlight areas of distinction and overlap, and propose a streamlined diagnostic workup for patients presenting with this cutaneous reaction pattern. Because the systemic disease associations and requisite workup are similar, and the etiopathogenesis is poorly understood but likely similar among these entities, we propose the simplified unifying term "reactive granulomatous dermatitis" to encompass these entities.

Coccidioidomycosis.

Coccidioidomycosis is a common, environmentally acquired, pulmonary fungal infection in arid and semi-arid regions of the West, especially Arizona and California. The infection is frequently associated with striking cutaneous manifestations. Reactive, immunologically mediated eruptions include erythema nodosum, a generalized exanthem, Sweet syndrome, and reactive granulomatous dermatitis. Less commonly, the skin can harbor the actual organisms as a result of dissemination from the lungs. Dermatologists may play a key role in the recognition of coccidioidomycosis