Interstitial 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.

P92 Cutaneous manifestations of myelodysplastic syndrome: a systematic review

Abstract A variety of associations between cutaneous manifestations and myelodysplastic syndrome (MDS) have been described, but the frequency is unknown. The presence of cutaneous manifestations may have therapeutic and prognostic significance, as the presence thereof has been reported to be associated with poor prognosis or acute myeloid leukaemia (AML) progression, or may precede the diagnosis of MDS [Farah C, Bulai Livideanu C, Jegu J et al. Prevalence and prognostic value of cutaneous manifestations in patients with myelodysplastic syndrome. J Eur Acad Dermatol Venereol 2010; 24:1171–5; Ghoufi L, Ortonne N, Ingen-Housz-Oro S et al. Histiocytoid Sweet syndrome is more frequently associated with myelodysplastic syndromes than the classical neutrophilic variant: a comparative series of 62 patients. Medicine (Baltimore) 2016; 95:e3033]. We aimed to determine the types and prevalence of cutaneous manifestations in MDS, treatment options and prognosis associated with specific cutaneous manifestations and MDS subtypes. PubMed, MEDLINE and Embase were searched from inception up to 26 January 2023 for studies reporting cutaneous manifestations of MDS in adults aged ≥ 18 years, as per the World Health Organization classification. Case reports and case series were included. The review was registered with PROSPERO (CRD42021293140). In total, 92 studies were included (case reports n = 71, case series n = 21), consisting of 140 patients [98 male, mean age 61.0 (SD 15.4)]. We identified six common cutaneous manifestations: neutrophilic, e.g. Sweet syndrome and pyoderma gangrenosum (n = 66); vasculitis, e.g. leucocytoclastic vasculitis and Behçet disease (n = 21); granulomatous, e.g. granuloma annulare and interstitial granulomatous dermatitis (n = 8); connective tissue disease (CTD), e.g. dermatomyositis (n = 7); panniculitis (n = 4); immunobullous (n = 2); and other (n = 30). Sweet syndrome (81.8%) and pyoderma gangrenosum (18.2%) were the commonest presentations of neutrophilic dermatosis. Cutaneous features either occurred at time of MDS diagnosis in 24.7%, preceded the diagnosis in 36.1% (mean 17 months; range 0.5–216), or after diagnosis in 39.2% (mean 20.6 msonths; range 1–132). Prognosis was poor (40.2% death) with 34.1% progressing to acute myeloid leukaemia (AML), 50% of which had neutrophilic dermatosis. Death occurred in 38.5% of neutrophilic dermatoses (median time from onset of cutaneous manifestation: 12 months), 50% of vasculitis (7.5 months), 62.5% of granulomatous (15.5 months), 14.3% of CTD (7 months), and none reported in immunobullous and panniculitis. Granulomatous skin lesions had the poorest prognosis, 60% of which had progressed to AML. This systematic review highlights the range of cutaneous manifestations associated with myelodysplastic syndrome. Of note, we found that the majority of cases progressing to AML were associated with neutrophilic dermatoses overall; however, granulomatous skin lesions had the poorest prognosis with the highest proportion progressing to AML. We speculate that these manifestations may confer an increase in risk of transformation, compared with other cutaneous changes.

BH10 Granulomatous scarring alopecia associated with rheumatoid arthritis: a case report with distinct folliculocentric granulomas histologically mimicking granulomatous alopecia areata

Abstract A 54-year-old woman presented with an 8-month history of a superficial erythematous skin lesion on the lower quadrant of her left breast and scarring hair loss in the vertex confirmed by diffuse central alopecia with erythema and tufted hairs. She also reported an 8-year history of seropositive rheumatoid arthritis and a history of breast cancer that was treated by surgery, followed by radiotherapy and tamoxifen. On histological examination, punch biopsy of the scalp showed a distinct folliculocentric pattern of multi­nucleated giant cells associated with a dense lymphocytic infiltrate in the hair follicular isthmic and infundibular areas extending into the subcutis, with some hair follicular tufting. Immunohistochemistry confirmed the T-cell nature of the lymphocytes. Punch biopsy of the breast showed noncaseating granulomas in the upper and lower dermis. This folliculocentric pattern was well demarcated and not associated with a granulomatous reaction to other skin adnexa. The interfollicular areas were relatively spared. There were no significant lymphocyte epidermotropism, Pautrier microabscesses or atypical lymphocytes. The differential diagnosis of the scalp included granulomatous folliculotropic mycosis fungoides; however, in our case, there was association with longstanding rheumatoid arthritis. Other differential diagnoses included granulomatous drug reaction and chronic infections such as mycobacteria and fungi. A very similar folliculocentric pattern has been described in only a handful of extremely rare cases of granulomatous alopecia areata (Wilk M, Zelger BG, Zelger B. Granulomatous alopecia areata. J Cutan Pathol 2014; 41:329–31); however, the granulomas are mainly in the hair bulb and spare the higher section of the hair follicle. The lesion in the breast was an area of previous radiotherapy for breast cancer. Other working diagnoses of the breast lesion included interstitial granulomatous dermatitis and palisading and neutrophilic dermatitis. Treatment consisted of potent topical and systemic steroids, immunosuppression, phototherapy and tumour necrosis factor-α inhibitors. Spontaneous resolution, periods of flares and remission, and treatment-resistant forms have been described. We have reported a case of scarring alopecia with a distinct pattern of folliculocentric noncaseating granulomas associated with granulomatous dermatitis in the breast as a cutaneous manifestation of rheumatoid arthritis. This hair loss is a result of an autoimmune-mediated reaction to the skin and hair follicles. Although folliculocentric noncaseating granulomas have been described in the hair bulb in very rare case reports of granulomatous alopecia areata, this pattern of folliculocentric isthmic and infundibular granulomas has not been clearly described before and needs to be better studied. Early diagnosis by skin biopsy is needed to start treatment in order to avoid permanent scarring hair loss.

The Free Sign in morphea and other sclerosing disorders: A clue to the presence of early sclerosis?

The Floating Sign is a histopathologic clue to the diagnosis of autoimmune sclerosing skin disorders such as morphea and interstitial granulomatous dermatitis (IGD). On the other hand, the "free-floating" sign has been associated with neoplasms, for example, dermatofibroma and interstitial mycosis fungoides. Herein, we report the Free Sign in sclerosing skin disorders. In a case-control study, we applied detailed histopathologic definitions of Floating Sign and Free Sign to assess their presence in morphea, IGD, and other sclerosing disorders. Free Sign was present in most cases of morphea (46/55, 84%) and IGD (7/13, 54%) but not necrobiosis lipoidica (NL) (6/14, 42.8%) or sclerodermoid graft versus host disease (SGVHD) (2/7, 28.5%). The sensitivity and specificity of Free Sign for morphea versus other disorders was 84% and 56%, respectively. Floating Sign was not identified in most cases: NL (3/14, 21.4%), SGVHD (1/7, 14.2%), morphea (5/55, 9%), IGD (1/13, 7.7%). The diagnostic sensitivity of Floating Sign in morphea was 9%. The Free Sign was present in most cases of morphea in our series and may represent a clue to the presence of evolving sclerosis. Free Sign may be seen in other sclerosing disorders. Technical artifact is a potential cause of a false-positive Free Sign.

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.

Concurrent Interstitial Granulomatous Dermatitis and TNF-α Antagonist-Induced Lupus Syndrome Secondary to Adalimumab for Crohn's Disease.

Tumor necrosis factor (TNF) antagonists have revolutionized management for various autoimmune and inflammatory conditions, including rheumatoid arthritis (RA), inflammatory bowel disease, hidradenitis suppurativa, psoriatic arthritis, and plaque psoriasis. However, adverse effects may necessitate switching to another biologic with a different mechanism of action. Here we report TNF-α antagonist-induced lupus syndrome (TAILS) revealed by interstitial granulomatous dermatitis (IGD), in the atypical context of Crohn's disease (CD).

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

To the Editor: Cutaneous granulomatous eruptions occur in response to various stimuli such as medications, systemic and autoimmune diseases, and internal malignancies. Variable clinical patterns and histologic subtypes may occur with these cutaneous eruptions, including palisaded neutrophilic and granulomatous dermatitis (PNGD), interstitial granulomatous dermatitis (IGD), and interstitial granulomatous drug reactions.1Rosenbach M. English III, J.C. Reactive granulomatous dermatitis: a review of palisaded neutrophilic and granulomatous dermatitis, interstitial granulomatous dermatitis, interstitial granulomatous drug reaction, and a proposed reclassification.Dermatol Clin. 2015; 33: 373-387https://doi.org/10.1016/j.det.2015.03.005Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar An expanding number of reports detail overlapping clinical and histologic features and similar associated systemic diseases, often leading to ambiguity and confusion among clinicians. PNGD classically demonstrates symmetric, skin-colored or erythematous umbilicated or crusted papules, often presenting on the elbows and extremities, with histopathologic findings of interstitial neutrophils and histiocytes, occasional leukocytoclastic vasculitis (30% of cases), and small granulomas; however, the spectrum of cutaneous morphologies and anatomic locations reported with histopathology consistent with PNGD has expanded.1Rosenbach M. English III, J.C. Reactive granulomatous dermatitis: a review of palisaded neutrophilic and granulomatous dermatitis, interstitial granulomatous dermatitis, interstitial granulomatous drug reaction, and a proposed reclassification.Dermatol Clin. 2015; 33: 373-387https://doi.org/10.1016/j.det.2015.03.005Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar,2Chu P. Connolly M.K. LeBoit P.E. The histopathologic spectrum of palisaded neutrophilic and granulomatous dermatitis in patients with collagen vascular disease.Arch Dermatol. 1994; 130: 1278-1283Crossref PubMed Scopus (231) Google Scholar Similarly, the definition of IGD has evolved, with an initial description of an asymptomatic, firm, palpable, linear band on the upper portion of the trunk with histopathologic changes of variable interstitial histiocytes often surrounding areas of abnormal collagen producing the characteristic “clefting” and “floating sign” in patients with inflammatory arthritis.1Rosenbach M. English III, J.C. Reactive granulomatous dermatitis: a review of palisaded neutrophilic and granulomatous dermatitis, interstitial granulomatous dermatitis, interstitial granulomatous drug reaction, and a proposed reclassification.Dermatol Clin. 2015; 33: 373-387https://doi.org/10.1016/j.det.2015.03.005Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar,3Caplan A. Wanat K. English III, J.C. Rosenbach M. Reactive granulomatous dermatitis (interstitial granulomatous dermatitis, palisaded neutrophilic and granulomatous dermatitis, and variants).in: Rongioletti F. Smoller B. New and Emerging Entities in Dermatology and Dermatopathology. 1st ed. Springer Nature, 2021: 423-445Crossref Google Scholar However, these classic subcutaneous cords may be present in <10% of cases.1Rosenbach M. English III, J.C. Reactive granulomatous dermatitis: a review of palisaded neutrophilic and granulomatous dermatitis, interstitial granulomatous dermatitis, interstitial granulomatous drug reaction, and a proposed reclassification.Dermatol Clin. 2015; 33: 373-387https://doi.org/10.1016/j.det.2015.03.005Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar,3Caplan A. Wanat K. English III, J.C. Rosenbach M. Reactive granulomatous dermatitis (interstitial granulomatous dermatitis, palisaded neutrophilic and granulomatous dermatitis, and variants).in: Rongioletti F. Smoller B. New and Emerging Entities in Dermatology and Dermatopathology. 1st ed. Springer Nature, 2021: 423-445Crossref Google Scholar,4Rodríguez-Garijo N. Bielsa I. Mascaró Jr., J.M. et al.Reactive granulomatous dermatitis as a histological pattern including manifestations of interstitial granulomatous dermatitis and palisaded neutrophilic and granulomatous dermatitis: a study of 52 patients.J Eur Acad Dermatol Venereol. 2021; 35: 988-994https://doi.org/10.1111/jdv.17010Crossref PubMed Scopus (11) Google Scholar Other presentations include symmetric erythematous/violaceous patches or plaques on the proximal aspects of the trunk and limbs, skin-colored papules, annular plaques, subcutaneous nodules, and papules on the elbow (classically, a sign of PNGD).1Rosenbach M. English III, J.C. Reactive granulomatous dermatitis: a review of palisaded neutrophilic and granulomatous dermatitis, interstitial granulomatous dermatitis, interstitial granulomatous drug reaction, and a proposed reclassification.Dermatol Clin. 2015; 33: 373-387https://doi.org/10.1016/j.det.2015.03.005Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar,3Caplan A. Wanat K. English III, J.C. Rosenbach M. Reactive granulomatous dermatitis (interstitial granulomatous dermatitis, palisaded neutrophilic and granulomatous dermatitis, and variants).in: Rongioletti F. Smoller B. New and Emerging Entities in Dermatology and Dermatopathology. 1st ed. Springer Nature, 2021: 423-445Crossref Google Scholar Importantly, the underlying associations in PNGD and IGD are similar. PNGD is reported most often in the setting of lupus and connective tissue diseases but may occur in inflammatory arthritis, lymphoproliferative disease, and other inflammatory settings.1Rosenbach M. English III, J.C. Reactive granulomatous dermatitis: a review of palisaded neutrophilic and granulomatous dermatitis, interstitial granulomatous dermatitis, interstitial granulomatous drug reaction, and a proposed reclassification.Dermatol Clin. 2015; 33: 373-387https://doi.org/10.1016/j.det.2015.03.005Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar,3Caplan A. Wanat K. English III, J.C. Rosenbach M. Reactive granulomatous dermatitis (interstitial granulomatous dermatitis, palisaded neutrophilic and granulomatous dermatitis, and variants).in: Rongioletti F. Smoller B. New and Emerging Entities in Dermatology and Dermatopathology. 1st ed. Springer Nature, 2021: 423-445Crossref Google Scholar IGD now includes associations with connective tissue diseases, including lupus, lymphoproliferative diseases, and other inflammatory disease states.1Rosenbach M. English III, J.C. Reactive granulomatous dermatitis: a review of palisaded neutrophilic and granulomatous dermatitis, interstitial granulomatous dermatitis, interstitial granulomatous drug reaction, and a proposed reclassification.Dermatol Clin. 2015; 33: 373-387https://doi.org/10.1016/j.det.2015.03.005Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar,3Caplan A. Wanat K. English III, J.C. Rosenbach M. Reactive granulomatous dermatitis (interstitial granulomatous dermatitis, palisaded neutrophilic and granulomatous dermatitis, and variants).in: Rongioletti F. Smoller B. New and Emerging Entities in Dermatology and Dermatopathology. 1st ed. Springer Nature, 2021: 423-445Crossref Google Scholar Interstitial granulomatous drug reaction (referred to separately as a distinct entity from “drug-induced forms of IGD”) was initially described as annular erythematous or violaceous plaques located on the inner portion of the arms, proximal aspect of the inner portion of the thighs, proximal aspect of the trunk, and intertriginous areas and associated with the medication use.5Magro C.M. Crowson A.N. Schapiro B.L. The interstitial granulomatous drug reaction: a distinctive clinical and pathological entity.J Cutan Pathol. 1998; 25: 72-78https://doi.org/10.1111/j.1600-0560.1998.tb01693.xCrossref PubMed Scopus (190) Google Scholar The main histologic findings include diffuse interstitial histiocytes with granulomas surrounding piecemeal fragmentation of collagen, scant mucin without vasculitis, and interface dermatitis with vacuolar degeneration and areas of dyskeratotic keratinocytes with prominent tissue eosinophilia.5Magro C.M. Crowson A.N. Schapiro B.L. The interstitial granulomatous drug reaction: a distinctive clinical and pathological entity.J Cutan Pathol. 1998; 25: 72-78https://doi.org/10.1111/j.1600-0560.1998.tb01693.xCrossref PubMed Scopus (190) Google Scholar However, PNGD and IGD may also be seen with similar medications without the histologic changes described in interstitial granulomatous drug reactions.1Rosenbach M. English III, J.C. Reactive granulomatous dermatitis: a review of palisaded neutrophilic and granulomatous dermatitis, interstitial granulomatous dermatitis, interstitial granulomatous drug reaction, and a proposed reclassification.Dermatol Clin. 2015; 33: 373-387https://doi.org/10.1016/j.det.2015.03.005Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar We encourage using “reactive granulomatous dermatitis” (RGD) as a unifying term to describe these overlapping entities, simplify the nomenclature, and provide a framework for dermatologists to use when evaluating these patients (Fig 1). This terminology has already been used in various circumstances by dermatologists and dermatopathologists.1Rosenbach M. English III, J.C. Reactive granulomatous dermatitis: a review of palisaded neutrophilic and granulomatous dermatitis, interstitial granulomatous dermatitis, interstitial granulomatous drug reaction, and a proposed reclassification.Dermatol Clin. 2015; 33: 373-387https://doi.org/10.1016/j.det.2015.03.005Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar,3Caplan A. Wanat K. English III, J.C. Rosenbach M. Reactive granulomatous dermatitis (interstitial granulomatous dermatitis, palisaded neutrophilic and granulomatous dermatitis, and variants).in: Rongioletti F. Smoller B. New and Emerging Entities in Dermatology and Dermatopathology. 1st ed. Springer Nature, 2021: 423-445Crossref Google Scholar,4Rodríguez-Garijo N. Bielsa I. Mascaró Jr., J.M. et al.Reactive granulomatous dermatitis as a histological pattern including manifestations of interstitial granulomatous dermatitis and palisaded neutrophilic and granulomatous dermatitis: a study of 52 patients.J Eur Acad Dermatol Venereol. 2021; 35: 988-994https://doi.org/10.1111/jdv.17010Crossref PubMed Scopus (11) Google Scholar Although RGD may represent a spectrum, with patients with PNGD-like RGD, IGD-like RGD, or even polycyclic or granuloma annulare–like RGD (RGD differing from classic granuloma annulare by histology, specifically the lack of increased mucin levels),3Caplan A. Wanat K. English III, J.C. Rosenbach M. Reactive granulomatous dermatitis (interstitial granulomatous dermatitis, palisaded neutrophilic and granulomatous dermatitis, and variants).in: Rongioletti F. Smoller B. New and Emerging Entities in Dermatology and Dermatopathology. 1st ed. Springer Nature, 2021: 423-445Crossref Google Scholar the overarching term is a helpful concept for clinicians and pathologists to guide appropriate evaluation for systemic disease and search for potential triggers. Patients presenting with any of these 3 entities require similar systemic evaluation, medical history review, probing regarding medications, and evaluation for potential triggers (Table Ⅰ). Using the umbrella terminology “RGD” allows for a more efficient systematic workup and treatment initiation for patients with granulomatous inflammation.Table IReactive granulomatous dermatitis (palisaded neutrophilic and granulomatous dermatitis, interstitial granulomatous dermatitis, and interstitial granulomatous drug reaction)DermatitisClinical featuresHistopathologyAssociationsWorkupPNGDSymmetric, smooth, umbilicated, or crusted, skin-colored to erythematous papules found primarily on the elbows and extremities∗Denotes original descriptions. Evolving definitions and descriptions include many overlapping clinical morphologies between PNGD and IGD.Early: neutrophil predominant inflammation, karyhorrectic debris, leukocytoclastic vasculitis, minimal mucinLate: piecemeal collagen degeneration, small granulomas, histiocytic palisadesSystemic disease (SLE, inflammatory arthritis, ANCA associated vasculitis, limited systemic sclerosis, Sjögren syndrome, inflammatory arthritis)Hematologic disorders (acute myelogenous leukemia, multiple myeloma, lymphoma, IgA gammopathy, anemia, thrombocytopenia, leukemia, lymphoma, and myelodysplastic disorders)Solid organ malignancies: breast, endometrial, lung, esophagealInfections: cellulitis, hepatitis, streptococcal infection, AIDSMedications: in particular, biologics, antihypertensives, and antiseizures; however, many case reports exist for a range of medications3Caplan A. Wanat K. English III, J.C. Rosenbach M. Reactive granulomatous dermatitis (interstitial granulomatous dermatitis, palisaded neutrophilic and granulomatous dermatitis, and variants).in: Rongioletti F. Smoller B. New and Emerging Entities in Dermatology and Dermatopathology. 1st ed. Springer Nature, 2021: 423-445Crossref Google ScholarANA, ANCA, double stranded DNA, anti-La(SS-B) and anti-Ro(SS-A) antibodies, anti-Scl70, anticentromere, RF, antiCCP†Evaluation based on patients’ signs and symptoms can be expanded to less frequently associated systemic diseases, including mixed cryoglobulinemia, undifferentiated connective tissue disease, erythema elevatum diutinum, ankylosing spondylitis, Takayasu arteritis, type 1 diabetes mellitus, sarcoidosis, ulcerative colitis, celiac disease, pernicious anemia, primary biliary cirrhosis, antiphospholipid antibody syndrome, polymyositis, uveitis, vitiligo, chronic inflammatory demyelinating polyneuropathy, Behçet disease, and multiple sclerosis.3Age-appropriate cancer screeningsCBC with differential serum protein electrophoresis/immunofixation electrophoresis and serum free light chains, chest radiographyReview supplements, diet, medications, including less frequently associated medicationsIGDFirm, asymptomatic, linear truncal bands in patients with inflammatory arthritis∗Denotes original descriptions. Evolving definitions and descriptions include many overlapping clinical morphologies between PNGD and IGD.Interstitial inflammation characterized by histiocytes frequently surrounding the foci of abnormal collagen and “clefting away”; absence of vasculitis and mucinIGDRErythematous-to-violaceous, often annular, plaques on the inner portion of the arms, proximal medial aspect of the thighs, trunk, and intertriginous locations in the setting of medicationsDiffuse interstitial histiocytes with granulomas surrounding degenerating collagen, scant mucin with absent vasculitis, interface dermatitis with basal vacuolar degeneration along with areas of dyskeratotic keratinocytes and prominent eosinophiliaMedications: antihypertensives (in particular, calcium channel blockers, β blockers, ACE inhibitors) and lipid-lowering drugs; however, many case reports exist for a range of medications3Caplan A. Wanat K. English III, J.C. Rosenbach M. Reactive granulomatous dermatitis (interstitial granulomatous dermatitis, palisaded neutrophilic and granulomatous dermatitis, and variants).in: Rongioletti F. Smoller B. New and Emerging Entities in Dermatology and Dermatopathology. 1st ed. Springer Nature, 2021: 423-445Crossref Google ScholarAdapted from Rosenbach and English,1Rosenbach M. English III, J.C. Reactive granulomatous dermatitis: a review of palisaded neutrophilic and granulomatous dermatitis, interstitial granulomatous dermatitis, interstitial granulomatous drug reaction, and a proposed reclassification.Dermatol Clin. 2015; 33: 373-387https://doi.org/10.1016/j.det.2015.03.005Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar Dermatol Clin (2015).ACE, Angiotensin-converting enzyme; ANA, antinuclear antibody; ANCA, antineutrophil cytoplasmic antibody; CBC, complete blood cell count; CCP, cyclic citrullinated peptide; IGD, interstitial granulomatous dermatitis; IGDR, interstitial granulomatous drug reaction; PNGD, palisaded neutrophilic and granulomatous dermatitis; RF, rheumatoid factor; SLE, systemic lupus erythematosus.∗ Denotes original descriptions. Evolving definitions and descriptions include many overlapping clinical morphologies between PNGD and IGD.† Evaluation based on patients’ signs and symptoms can be expanded to less frequently associated systemic diseases, including mixed cryoglobulinemia, undifferentiated connective tissue disease, erythema elevatum diutinum, ankylosing spondylitis, Takayasu arteritis, type 1 diabetes mellitus, sarcoidosis, ulcerative colitis, celiac disease, pernicious anemia, primary biliary cirrhosis, antiphospholipid antibody syndrome, polymyositis, uveitis, vitiligo, chronic inflammatory demyelinating polyneuropathy, Behçet disease, and multiple sclerosis.3Caplan A. Wanat K. English III, J.C. Rosenbach M. Reactive granulomatous dermatitis (interstitial granulomatous dermatitis, palisaded neutrophilic and granulomatous dermatitis, and variants).in: Rongioletti F. Smoller B. New and Emerging Entities in Dermatology and Dermatopathology. 1st ed. Springer Nature, 2021: 423-445Crossref Google Scholar Open table in a new tab Adapted from Rosenbach and English,1Rosenbach M. English III, J.C. Reactive granulomatous dermatitis: a review of palisaded neutrophilic and granulomatous dermatitis, interstitial granulomatous dermatitis, interstitial granulomatous drug reaction, and a proposed reclassification.Dermatol Clin. 2015; 33: 373-387https://doi.org/10.1016/j.det.2015.03.005Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar Dermatol Clin (2015). ACE, Angiotensin-converting enzyme; ANA, antinuclear antibody; ANCA, antineutrophil cytoplasmic antibody; CBC, complete blood cell count; CCP, cyclic citrullinated peptide; IGD, interstitial granulomatous dermatitis; IGDR, interstitial granulomatous drug reaction; PNGD, palisaded neutrophilic and granulomatous dermatitis; RF, rheumatoid factor; SLE, systemic lupus erythematosus. None disclosed.

Drug interstitial granulomatous dermatitis caused by warfarin

Drug interstitial granulomatous dermatitis caused by warfarin

Cutaneous paraneoplastic presentation of colon cancer in a patient with history of ureterosigmoidostomy

Ureterosigmoidostomy was commonly utilized as a procedure for continent urinary diversion. However, ureterosigmoidostomy is associated with complications such as infection, electrolyte disturbances, and neoplasia development. A 40-year-old Caucasian male presented with acute left flank pain. Past medical history was significant for bladder exstrophy for which ureterosigmoidostomy urinary diversion was performed during childhood. On physical exam, multiple circular erythematous patches were scattered across the forearms that had been presented for 2 years. Cross-sectional imaging demonnttated an ill-defined mass at the site of ureteral implantation with associated severe left hydroureteronephrosis. Endoscopy revealed a mass at the site of ureteral implantation and biopsy demonstrated invasive, poorly differentiated adenocarcinoma. The dermatosis was diagnosed as interstitial granulomatous dermatitis, a rare inflammatory skin condition associated with underlying autoimmune disease or malignancy. Patient elected operative management with left nephrectomy, sigmoidectomy, and ileal conduit diversion. Ihis case demonnttates a rare presentation of cutaneous paraneoplastic syndrome after development of colon cancer after ureterosigmoidostomy. Ureterooolonic urinary diversion has a demonnttaaie risk of neoplasia development at the anastomotic site, requiring routine endoscopic surveillance.

Interstitial granulomatous dermatitis associated with myelofibrosis.

Interstitial granulomatous dermatitis associated with myelofibrosis.

A prospective cohort study comparing the performance of interferon gamma release assays in autoimmune skin diseases

To the Editor: Autoimmune disease patients are more likely to reactivate latent tuberculosis (TB) than the general population, and the risk increases in immunosuppressed patients.1Arenas Miras Mdel M. Hidalgo-Tenorio C. Jiménez-Gamiz P. et al.Diagnosis of latent tuberculosis in patients with systemic lupus erythematosus: T.SPOT.TB versus tuberculin skin test.Biomed Res Int. 2014; 2014: 291031PubMed Google Scholar TB screening is recommended prior to immunosuppressive therapy or clinical trial enrollment.2Jick S.S. Lieberman E.S. Rahman M.U. et al.Glucocorticoid use, other associated factors, and the risk of tuberculosis.Arthritis Rheum. 2006; 55: 9-26Crossref PubMed Scopus (308) Google Scholar,3Hamilton C.D. Tuberculosis in the cytokine era: what rheumatologists need to know.Arthritis Rheum. 2003; 48: 2085-2091Crossref PubMed Scopus (55) Google Scholar Two interferon gamma release assays (IGRAs), QuantiFERON-TB Gold Plus (QFT-Plus; Qiagen) and T-SPOT.TB test (Oxford Immunotec), demonstrate similar sensitivity and specificity in healthy populations.4QuantiFERON-TB Gold Frequently Asked Questions. Qiagen.https://www.quantiferon.com/wp-content/uploads/2017/05/PROM-10157_FAQs-Health-Professionals-Rev001v02.pdfDate accessed: January 3, 2020Google Scholar However, immunosuppressed patients are more likely to have an indeterminate or invalid IGRA due to an inadequate immune response.5Aabye M.G. Ravn P. PrayGod G. et al.The impact of HIV infection and CD4 cell count on the performance of an interferon gamma release assay in patients with pulmonary tuberculosis.PLoS One. 2009; 4: e4220Crossref PubMed Scopus (79) Google Scholar This study compares the performance of the QFT-Plus and T-SPOT.TB tests in autoimmune skin disease patients. Clinical and laboratory information were collected from the medical records at the University of Pennsylvania. IGRAs were performed according to the manufacturers' recommendations. The QFT-Plus test results were reported as positive, negative, or indeterminate. The T-Spot.TB test results were reported as positive, negative, borderline, or invalid. The QFT-Plus test indeterminate and the T-Spot.TB test invalid results were not clinically interpretable. A borderline result was designed to increase the reliability of results close to the cut-off value to reduce the incidence of false negatives or positives. Invalid T-Spot.TB test results were considered equivalent to QFT-Plus test indeterminate results. Statistical analysis was performed using the McNemar and Fisher tests. Clinical characteristics of the patients (n = 101) are described in Table I. Lymphopenia was defined as <1000 lymphocytes/μL, and 16 (15.8%) patients were diagnosed with lymphopenia. A total of 26.7% of patients did not undergo lymphocyte count testing within the 6 months. Sixteen cases (15.6%) showed indeterminate QFT-Plus test results, and 1 case (1.0%) showed an invalid T-SPOT.TB test result. One case tested positive for both IGRAs. There was a significantly higher frequency of indeterminate QFT-Plus test results compared with invalid T-SPOT.TB test results (P < .05, odds ratio 16 [2.49-670.96]). No associations between age (P = .68), immunosuppressive medication (P = .44), hydroxychloroquine (P = .77), combined antimalarial use (P = .23), lupus erythematosus (P = .49) or dermatomyositis (P = .90) diagnoses, lymphopenia (P = .72), and indeterminate/invalid results were found. Eleven patients had a previous indeterminate QuantiFERON Gold result, of whom 6 (55%) had a subsequent indeterminate QFT-Plus result upon retesting.Table IClinical characteristics and results of tuberculosis screening of 101 autoimmune skin disease patientsCharacteristicsIndeterminate/invalid (n = 17)Determinate (n = 84)P valueMedian age, y (IQR)55 (41.0-62.5)57 (44.0-62.8).68Sex, n (%)N/A Male1 (5.9)15 (17.9) Female16 (94.1)69 (82.1)Race, n (%)N/A Black2 (11.8)18 (21.4) White14 (82.3)64 (76.2) Asian1 (5.9)2 (2.4)Ethnicity, n (%)N/A Hispanic0 (0.0)4 (4.8) Non-Hispanic17 (100.0)80 (95.2)Diagnosis, n (%) Lupus7 (41.2)29 (34.5).49 Dermatomyositis9 (52.9)35 (41.7).90 Other∗Other autoimmune skin disorder diagnoses include morphea, mixed connective tissue disease, undifferentiated connective tissue disease, sarcoidosis, scleroderma, Sjogren syndrome, Sweet syndrome, eosinophilic fasciitis, erythema multiforme, interstitial granulomatous dermatitis, lichen planus pilaris, and mucous membrane pemphigoid.1 (5.9)20 (23.8)N/AHCQ use, n (%) No4 (23.5)16 (19.0).77 Yes13 (76.5)68 (81.0)Immunosuppressive medication use,†Immunosuppressive medications include methotrexate, mycophenolate, azathioprine, intravenous immunoglobulin, dapsone, and cyclosporine. n (%) No4 (23.5)37 (44.0).44 Yes13 (76.5)47 (56.0)Lymphopenia, n (%) No9 (53.0)49 (58.3).72 Yes4 (23.5)12 (14.3) N/A4 (23.5)23 (27.4)HCQ, Hydroxychloroquine; IQR, interquartile range, N/A, not available.∗ Other autoimmune skin disorder diagnoses include morphea, mixed connective tissue disease, undifferentiated connective tissue disease, sarcoidosis, scleroderma, Sjogren syndrome, Sweet syndrome, eosinophilic fasciitis, erythema multiforme, interstitial granulomatous dermatitis, lichen planus pilaris, and mucous membrane pemphigoid.† Immunosuppressive medications include methotrexate, mycophenolate, azathioprine, intravenous immunoglobulin, dapsone, and cyclosporine. Open table in a new tab HCQ, Hydroxychloroquine; IQR, interquartile range, N/A, not available. In this single-center autoimmune disease population, we demonstrated that the T-SPOT.TB test provided a definitive result significantly more often than the QFT-Plus test. One reason may be due to the differing immunological technique. The QFT-Plus test uses enzyme-linked immunosorbent assay to measure interferon gamma at the whole-blood level, whereas the TSPOT.TB test uses enzyme-linked immune absorbent spot to detect interferon gamma production at a single cell level. Additionally, the T-SPOT.TB test utilizes a cell counting technique to use fixed lymphocyte numbers prior to running the assay, which is beneficial for patients with lymphopenia. However, these findings may not be translatable to TB testing of psoriasis patients receiving biologics. Based on our findings, approximately half of patients with an indeterminate QFT-Plus will have to retest, which can be financially burdensome and delay clinical trial enrollment. Establishing the best TB screening for these patients is clinically important as inconclusive IGRA results can delay critical therapies. This study suggests that in the case of a QFT-Plus test indeterminate result, the T-SPOT.TB test should be the first-line TB-screening test in the autoimmune skin disease population. None disclosed.

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.

Abstract 13129: Chest Pain and Inflammation: A Story Where Hickam’s Dictum Prevailed

A 39-year-old male presented with a chief complaint of chest pain that worsened with deep breathing for one day. He was found to be tachycardic, with distant heart sounds and a skin nodule over his right upper extremity. ECG revealed diffuse ST elevations and PR segment depressions with TTE showing a small pericardial effusion. Troponin I was 8.98 ng/mL and NT-proBNP was 981 pg/mL. One day after admission, he developed respiratory distress, and repeat TTE showed a large pericardial effusion with collapse of the RV free wall during diastole with variation of mitral and tricuspid valve inflows consistent with tamponade. Pulsus paradoxus was 24 mmHg and he was taken for pericardiocentesis. Skin nodule biopsy revealed nodular and interstitial granulomatous dermatitis. Anti-nuclear antibody and double stranded DNA antibody were positive with pericardial fluid cytology showing acute inflammation with lupus erythematosus cells. Based upon this constellation of findings, he was diagnosed with systemic lupus erythematosus (SLE) myopericarditis, and started on colchicine and immunosuppression, with resolution of symptoms. One week into hospitalization, the chest pain recurred but was sharp and substernal, with a rising troponin from 1.23 ng/mL to 8.23 ng/mL. TTE showed depressed LVEF of 45% and RCA territory hypokinesis without effusion. CTA PE showed no evidence of thromboembolism and CT coronary demonstrated mural thickening of the mid LAD and aneurysmal dilation of the left main to the LAD and left circumflex bifurcation concerning for vasculitis. The mid RCA was occluded, and patient was taken to the cardiac catherization laboratory revealing thrombotic occlusion of the proximal-to-mid RCA. Despite serial balloon dilation, thrombotic occlusion persisted, Aspiration thrombectomy evacuated organized thrombus prior to deployment of two overlapping drug-eluting stents in the proximal-to-mid RCA, restoring flow. TTE prior to discharge showed normal LVEF and no effusion. This case illustrates various cardiac manifestations of SLE and the unusual dynamic nature of this patient’s multiple presentations of chest pain. Avoiding “diagnostic anchoring” is important to diagnosing and treating conditions such as SLE, that can affect the heart in multiple ways.

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.

Interstitial granulomatous dermatitis following tocilizumab, a paradoxical reaction?

Interstitial granulomatous dermatitis (IGD) is a rare dermatosis generally seen in the setting of rheumatic diseases, but also hematological disorders, internal malignances, infections, or drug induced. Herein, we report an exceptional case of an IGD with a clear chronological association with tocilizumab onset and cessation in a patient with adult-onset Still's disease. We review the granulomatous cutaneous reactions so far reported with this novel therapy: sarcoidosis, granuloma annulare, and IGD. Tocilizumab is a humanized anti-interleukin 6 receptor monoclonal antibody useful for the treatment of various systemic inflammatory disorders. Lately, it has found useful also for granulomatous diseases such as giant cell arteritis and even a promising response in IGD. Therefore, we believe our case adds the possibility of an IGD presenting as a paradoxical reaction.

Dermatitis granulomatosa intersticial asociada a artritis (DGIaA). Caso clínico y revisión narrativa

Interstitial granulomatous dermatitis with arthritis is an unusual condition that occurs with skin and joint manifestations. Its cutaneous form, it is characterized by the formation of cords or “bands” in a linear arrangement (pathognomonic of this disease) or arciform or eruptions of papular type or in plates, being associated polyarthritis. We present a case of a DGIaA, with special attention to its clinical-pathological relevance to estabish diagnosis and subsequent treatment, making a bibliographic review.

Treatment of granuloma annulare and related granulomatous diseases with sulphasalazine: a series of 16 cases.

Granuloma annulare (GA) and the related annular elastolytic giant cell granuloma (AEGCG) and interstitial granulomatous dermatitis (IGD) are idiopathic histiocytic inflammatory disorders, which are frequently recalcitrant to treatment. Evaluate the efficacy of sulphasalazine in treating GA, AEGCG and IGD. Sixteen patients were identified with granulomatous disease who were treated with sulphasalazine between September 2015 and September 2019. Outcomes were based on patients' and providers' subjective evaluations. Sixteen patients were included in the study (ages 56-89, four male and twelve female). Previous treatments were attempted in fifteen patients. Clinical improvement was seen in fourteen patients (87.5%). Initial improvement was noted within a mean (SD) of 66.4 (35.1) days after starting therapy, with increasing benefits over time. Ten patients (62.5%) reported complete or near-complete clearance, three patients (18.8%) reported significant improvement, and one (6.3%) reported partial improvement. Twelve patients elected to stop or reduce therapy, resulting in relapse or worsening in five patients. Sulphasalazine may be considered as treatment for GA and GA-related conditions.

Histopathological Spectrum and Immunophenotypic Characterization of Symmetrical Drug-Related Intertriginous and Flexural Exanthema.

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a clinically very well-defined drug eruption, but the histopathological findings are still considered to be nonspecific. To characterize the histopathological and immunophenotypical features of SDRIFE. We performed a retrospective study that identified 11 biopsies from 9 patients with SDRIFE. The histopathological features were analyzed in conjunction with the immunohistochemical findings. The most common histopathological feature was basal cell vacuolization, which was often associated with necrotic keratinocytes and focal spongiosis. TIA1+ T cells and neutrophils were frequently detected in the epidermis and at the dermoepidermal junction. The dermal inflammatory infiltrate was mixed, consisting of CD3+ T cells, macrophages, granulocytes, low numbers of CD20+ B cells, and plasma cells. A combination of histopathological patterns was observed in 5 cases. The most frequent combined histopathological patterns were interface dermatitis, spongiotic dermatitis, and psoriasiform dermatitis. Other histopathological patterns found in different combinations were pustular dermatitis, perivascular and interstitial neutrophilic dermatitis, and interstitial granulomatous dermatitis. In the other 4 cases, a single histopathological pattern predominated, such as psoriasiform dermatitis, vacuolar interface dermatitis of erythema multiforme-like type, or superficial and deep perivascular and interstitial dermatitis with eosinophils and neutrophils. SDRIFE is characterized histologically by a vacuolar interface dermatitis induced by cytotoxic T lymphocytes and neutrophilic granulocytes. This pattern may be obscured by accompanying spongiotic, psoriasiform, or pustular features combined with a mixed superficial and sometimes deep dermal infiltrate.