Palisaded Neutrophilic And Granulomatous Dermatitis Research Articles

Palisaded Neutrophilic and Granulomatous Dermatitis-Like Reaction Associated with Wilms Tumor 1 Protein-Derived Peptide Vaccine: A Case and Review of the Literature

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is an inflammatory cutaneous reaction that is associated with underlying autoimmune diseases. In rare cases, PNGD has been attributed to systemic medications. Here we report one case of a cutaneous injection-site reaction that occurred after intradermal administration of an experimental Wilms Tumor 1 (WT1) protein-derived peptide vaccine in a woman being treated for recurrent ovarian cancer. This is the first reported case of a PNGD-like reaction associated with immunotherapy injections. In this article, we discuss this case and summarize the literature related to the diagnosis and management of PNGD, as well as other injection site reactions related to immunotherapies and experimental vaccines.

33714 Palisaded neutrophilic and granulomatous dermatitis in the setting of SRSF2-mutated chronic myelomonocytic leukemia: Case report and review of the literature

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a rare cutaneous histopathologic reaction pattern associated with several underlying disorders. Few cases of PNGD have been associated with hematologic malignancies, in particular with chronic myelomonocytic leukemia (CMML), a malignant hematopoietic disorder with features of myeloproliferative neoplasm and myelodysplastic syndrome. CMML is characterized by peripheral blood monocytosis and bone marrow dysplasia, and can be supported by an acquired clonal cytogenetic abnormality most commonly in TET2, SRSF2, ASXL1, RUNX1, NRAS, and CBL. We present a patient with a papulosquamous rash on the neck, chest, and shoulders with histomorphological features on the spectrum of PNGD. Subsequent lab workup demonstrated a persistent mild monocytosis, raising concern for CMML. The patient was referred to hematology-oncology for a bone marrow biopsy, which ultimately led to her diagnosis. Cytogenic studies of the bone marrow biopsy demonstrated mutations in SRSF2, IDH2, and ASXL1, which were strongly supportive of this diagnosis. After discussion at a multidisciplinary tumor board, treatment directed at the skin eruption alone was recommended. She was started on prednisone taper and demonstrated marked clinical improvement. PNGD in the context of CMML has been scarcely reported, with only 4 prior reports in the literature. Our patient is the fifth reported case, and the fourth case with confirmed underlying SRSF2 mutation. This is likely a novel and reproducible clinical-histopathologic-molecular subtype of reactive granulomatous disease. The findings in this case strengthen the previously made association between PNGD and SRSF2-mutated CMML, and may help better define a unique recognizable subtype for dermatopathologists.

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.

Palisaded neutrophilic and granulomatous dermatitis, A critical diagnosis in a severe lupus flare

Palisaded Neutrophilic And Granulomatous Dermatitis (PNGD) is a rare inflammatory cutaneous eruption associated with underlying systemic disease, commonly Systemic Lupus Erythematosus (SLE), rheumatoid arthritis, or Anti-Neutrophilic Cytoplasmic Autoantibody (ANCA)-associated vasculitis. Appropriate diagnosis is challenging, requiring coordination of care between medicine, dermatology, pathology, and rheumatology. We describe a 29-year-old female with SLE who developed eroded papules and erythematous, edematous plaques on the ear anti-helices, hands, and elbows during hospitalization for workup of acute on chronic abdominal pain. Biopsies showed an interstitial infiltrate of zonal collagen necrobiosis, consistent with typical PNGD histopathology, involving collagen inflammation surrounded by palisading neutrophils, histiocytes, karyorrhexis, and leukocytoclastic vasculitis. The association of ANCA-vasculitis makes differentiation between underlying autoinflammatory disease in PNGD from new vasculitis difficult; however, histopathology is key to distinguishing them. Treatment should focus on improvement of the underlying autoimmune condition. Adjuvant treatments are intralesional or systemic corticosteroids, hydroxychloroquine, or dapsone. Given the complexities of associated conditions, it is important to bring awareness of PNGD to the medical community for improved diagnostic accuracy and subsequent care.

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.

Generalized palisaded neutrophilic and granulomatous dermatitis—a cutaneous manifestation of chronic myelomonocytic leukemia? A clinical, histopathological, and molecular study of 3 cases

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is characterized by erythematous papules or plaques on trunk or limbs and is frequently associated with rheumatologic, autoimmune, or hematologic malignancies. Histopathology shows interstitial granulomas composed of epitheloid histiocytes in the reticular dermis with surrounding foci of collagen degeneration and variable neutrophilic inflammation. We report 3 cases of generalized PNGD associated with chronic myelomonocytic leukemia (CMML), a myelodysplastic/myeloproliferative neoplasm, which may show a variety of cutaneous manifestations. SRSF2 P95 hotspot mutations, found in 40%-50% of CMML cases, were retrospectively detected in skin and bone marrow biopsies of all 3 patients, in 1 of them already 5 years before CMML diagnosis. Generalized PNGD may represent a type of cutaneous manifestation of CMML. Because diagnosis of CMML is frequently difficult in cases with isolated persistent monocytosis and minimal dysplasia in the bone marrow, patients with a generalized PNGD should be evaluated for the presence of hematologic disorders including CMML, ideally supported by mutational analyses.

Interstitial Granulomatous Dermatitis Associated with Rheumatoid Arthritis.

Dear Editor: Interstitial granulomatous dermatitis (IGD) is a rare and peculiar disorder with cutaneous and joint manifestations1. IGD may be associated with rheumatologic and hematologic disorders of underlying malignancies2,3. Herein, we report a case of IGD associated with rheumatoid arthritis (RA). A 59-year-old Korean woman presented with multiple erythematous plaques on both extremities for 10 days (Fig. 1A). Upon physical examination, the plaques were linear shaped, non-tender, and palpable. She had been diagnosed with RA 17 years earlier. She had taken prednisolone, nonsteroidal anti-inflammatory drugs, and methotrexate to treat RA for 7 years. One month earlier, her arthritis symptoms had stabilized and the rheumatologist withdrew methotrexate. Laboratory test findings were non-specific except for an elevated C-reactive protein (CRP) level (7.12 mg/dl; normal range, 0.01~0.47 mg/dl) and erythrocyte sedimentation rate (ESR) (81 mm/h; normal range, 0~15 mm/h). Histopathologic findings indicated perivascular and interstitial lymphohistiocytic infiltration through the dermis and chronic granulomatous inflammation with collagen degeneration in the upper dermis. Immunohistochemically, most of the infiltrating inflammatory cells were CD 68-positive. Alcian blue staining revealed no mucin deposition in the areas of granulomatous inflammation (Fig. 2). Based on clinical and histological findings, she was diagnosed with IGD. A 7.5-mg methotrexate dose was given weekly and the daily prednisolone dose was increased from 5 mg to 15 mg. A topical 0.1% tacrolimus ointment and methylprednisolone cream were also applied daily for 2 months. The lesions were nearly cleared and ESR and CRP were found to be within normal limits after 2-month follow-up (Fig. 1B). Fig. 1 (A) Multiple, erythematous, palpable, and linear shaped plaques on both extremities. (B) Nearly clearing of lesions after a 2-month follow-up. Fig. 2 (A) A perivascular and interstitial lymphohistiocyte infiltration in the entire dermis (HE B: ×100, C: ×400). ... The most common clinical findings of IGD are asymptomatic multiple papules and plaques (70%~90% of cases)2. The rope sign was named for the linear prominent cutaneous cord-like lesions, considered pathognomic for IGD1. However, these lesions are not an essential feature, and are reported in only 9% of cases3. The histopathologic findings show interstitial CD 68-positive histiocyte infiltration around focally degenerated collagen2,4. Epidermal changes, mucin deposition, neutrophil and/or eosinophil infiltration, and vasculitis are usually absent 2. Differential diagnoses include interstitial granuloma annulare (IGA), interstitial granulomatous drug reaction (IGDR), and palisaded neutrophilic and granulomatous dermatitis (PNGD)1,2,4. In IGA, prominent mucin deposition and only focal interstitial infiltration could be found. Recent change of medication is present in IGDR, and IGDR presents with basal cell vacuolization and lichenoid changes with eosinophils2. Leukocytoclastic vasculitis and pandermal infiltration of neutrophil frequently present in early lesion of PNGD, and palisading granulomatous inflammation is the typical feature of fully developed one1. The pathogenesis of IGD may be associated with immune complex deposition caused by immune reactants of systemic inflammatory diseases5. Interestingly, IGD lesions in our case began to occur in association with the flare-up of RA after methotrexate withdrawal, although the causal relationship remains unknown. From our case we suggest that IGD should be considered among the differential diagnoses for patients with rheumatologic disease and cord-like skin lesions.

Palisaded neutrophilic and granulomatous dermatitis in a rheumatoid arthritis patient after treatment with adalimumab

ejd.2013.2197 Auteur(s) : Yoshinori Umezawa yoshinori.umezawa@jikei.ac.jp, Keigo Ito, Hidemi Nakagawa Department of Dermatology, The Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minatoku, Tokyo, 105-8461, Japan Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a rare disease occurring in patients with autoimmune diseases [1]. The clinical features are characterised by symmetrically distributed, skin coloured to erythematous, macropapular lesions with a smooth, ulcerated [...]

Combination therapy with intralesional triamcinolone and oral dapsone for management of palisaded neutrophilic and granulomatous dermatitis

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a rare granulomatous disease with limited therapeutic options. Herein we present a patient whose skin lesions recurred after surgery and oral steroids, but responded well to a combination of intralesional triamcinolone and oral dapsone.

Palisaded neutrophilic and granulomatous dermatitis associated with the initiation of etanercept in rheumatoid arthritis: a case report

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is an unusual entity with variable clinical manifestations and histopathological features. It is associated with a variety of immune-mediated systemic diseases, most commonly in rheumatoid arthritis. We report a 42-year-old female with a long-standing history of rheumatoid arthritis, presenting with multiple pruritic erythematous papules and nodules on the lower legs 1 month after beginning treatment with etanercept. Microscopic examination of a fully developed lesion showed a diffuse dense interstitial lymphohistiocytic infiltrate interspersed with palisaded granulomas consisting of epithelioid histiocytes and multinucleated giant cells surrounding central zones of degenerated collagen, neutrophils and leukocytoclastic debris. A diagnosis of PNGD was made on the basis of typical histopathologic features. Withdrawal of etanercept led to gradual resolution of the skin lesions, with no new skin lesions appearing afterwards. Although the correlation between the use of tumor necrosis factor-α (TNF-α) antagonists and the development of PNGD remains controversial and warrants further investigation, PNGD should be considered in the differential diagnosis of skin eruptions within a setting of anti-TNF-α therapy.

Palisaded neutrophilic and granulomatous dermatitis presenting in a patient with rheumatoid arthritis on adalimumab

Rheumatoid arthritis (RA) is a chronic inflammatory arthritis that can present with many unique cutaneous manifestations including palisaded neutrophilic and granulomatous dermatitis (PNGD). The authors present a case of PNGD in a RA patient on adalimumab therapy. The potential association of PNGD and adalimumab therapy is discussed as well as a review of the literature of granulomatous eruptions involving patients with RA who are receiving tumor necrosis factor-alpha inhibitor therapy.

Palisaded neutrophilic and granulomatous dermatitis associated with limited systemic sclerosis

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a condition that is characterized histopathologically by a characteristic pattern of granulomatous inflammation in the presence or absence of leukocytoclastic vasculitis. It has been associated with systemic diseases, especially autoimmune conditions such as rheumatoid arthritis and Behçet's disease. A 44-year-old woman with underlying limited systemic sclerosis presented with painful erythematous nodules located on her face and scalp. Histopathologic analysis confirmed a diagnosis of PNGD, which self-resolved within weeks of the biopsy. To our knowledge, this is the first report of a case of PNGD associated with systemic sclerosis. A review of the literature revealed that PNGD is a female-predominant disease that is most commonly associated with rheumatoid arthritis, followed closely by lupus erythematosus. Most patients with PNGD respond to treatment of the underlying systemic disease, although spontaneous resolution is not uncommonly observed.

Palisaded neutrophilic and granulomatous dermatitis: An unusual cutaneous manifestation of immune-mediated disorders

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is an uncommon skin eruption most often associated with rheumatoid arthritis and other immune-mediated diseases. We present 4 cases to familiarize rheumatologists with the clinical presentation and histopathology of PNGD. We report 4 cases to illustrate the clinical and histologic spectrum of this rare skin disease found in rheumatologic patients. The disease pathogenesis and treatment options are discussed. All 4 patients presented with symmetric erythematous-to-violaceous papules and plaques that, upon biopsy, revealed a dermatitis composed of variable numbers of histiocytes and neutrophils. Some cases responded to topical corticosteroid treatment or to dapsone, whereas others resolved spontaneously. PNGD is a rare cutaneous finding in patients with a variety of immune-mediated systemic diseases, most often rheumatoid arthritis. It is a benign condition that may spontaneously remit or may respond favorably to topical corticosteroids or dapsone.