Interstitial granulomatous dermatitis with arthritis
Department of Dermatology, New York University
A 54-year-old woman with a history of arthritis presented for a long-standing history of symmetric, indurated plaques on her thighs and lateral aspects of the trunk. Histopathologic examination of skin biopsy specimens was consistent with interstitial granulomatous dermatitis, and a diagnosis of interstitial granulomatous dermatitis with arthritis was made. Administration of topical potent glucocorticoids, intralesional glucocorticoids, and narrow-band ultraviolet B phototherapy, in addition to continuation of systemic glucocorticoids and methotrexate, resulted in improvement of her cutaneous and musculoskeletal disease.
A 54-year-old woman with a history of seronegative arthritis presented to Dermatologic Associates at the New York University Medical Center with an eight-year history of indurated plaques on her thighs and lateral aspects of the trunk. The skin lesions were noted to be largely symmetric in distribution, sharply demarcated, and occasionally pruritic. Her past medical history included the above-mentioned arthritis, mitral valve prolapse, and Barrett's esophagus. Additionally, she had previously been noted to have inguinal lymphadenopathy, and prior computed tomography scans had demonstrated adenopathy of her retroperitoneal and obturator nodes. Histopathologic evaluation of a right inguinal lymph node showed benign reactive changes. No family history of skin or rheumatologic diseases was reported. Her medications included methotrexate, prednisone, folic acid, risedronate, and esomeprazole. No drug allergies were reported.
Initiation of narrow-band ultraviolet B phototherapy as well as the use of potent topical and intralesional glucocorticoid administration resulted in improvement of the patient's disease.
Large, atrophic, erythematous, hyperpigmented, sharply-demarcated plaques with deep induration were present in a symmetric distribution on the lateral aspects of the trunk and thighs.
A complete blood count, comprehensive metabolic panel, erythrocyte sedimenation rate, serum protein electrophoresis, and serum immunofixation were normal. C-reactive protein was elevated at 11.1 mg/L and rheumatoid factor 15.1 IU/mL. Anti-nuclear antibody, anti-Ro antibody, anti-La antibody, anti-RNP antibody, anti-Smith antibody, cryoglobulin, cytoplasmic anti-neutrophilic cytoplasmic antibody, perinuclear anti-neutrophilic cytoplasmic antibody, and total Lyme antibody were negative.
There is a superficial and deep, perivascular and interstitial infiltrate of lymphocytes, eosinophils, and mononuclear histiocytes. Mononuclear histiocytes are scattered between collagen bundles and associated with mucin deposits, which are highlighted with a colloidal iron stain.
Interstitial granulomatous dermatitis with arthritis (IGDA) is an uncommon, idiopathic clinicopathologic designation first described in 1993 . It is likely that, given its relatively recent description as a distinct clinical entity and the variability of its clinical presentation, it is underrecognized. The initial clinical descriptions of IGDA recounted subcutaneous linear cords that were thought to be pathognomonic and that were labeled the rope sign . Since these initial cases were reported, other clinical presentations have been described, and the rope sign is no longer thought to be necessary for the diagnosis . Interstitial granulomatous dermatitis with arthritis can present as erythematous, hyperpigmented papules [3, 4], subcutaneous plaques [5, 6, 7], or annular lesions  that usually involve the lateral chest wall, abdomen, and/or the medial aspects of the thighs. The appearance of arthritis may occur prior to, concurrent with, or after the cutaneous presentation . The arthritis is typically thought to be non-erosive and not deforming although this is not universally the case.
Histopathologic features of IGDA include a dense, bottom-heavy or band-like , mixed infiltrate of mostly histiocytes in the mid-to-deep reticular dermis. The histiocytes can be observed in apposition to collagen and elastic fibers, with variable evidence of phagocytosis, and/or the histiocytes may form small rosettes that surround thick central collagen bundles . Neutrophils and eosinophils also are present in the infiltrate. No vasculitis is observed. Whether IGDA is an entity along the spectrum of palisaded neutrophilic and granulomatous dermatitis (PNGD) , which includes Churg-Strauss granuloma, cutaneous extravascular necrotizing granuloma, rheumatoid papules, and superficial ulcerating rheumatoid necrobiosis , or is a clinically distinct disease is controversial. The absence of vasculitis has been cited as supporting evidence that IGDA is a clinical entity distinct from PNGD [4, 25].
Interstitial granulomatous dermatitis with arthritis has been described in association with several autoimmune disorders that include rheumatoid arthritis [9, 10], systemic lupus erythematosus , primary antiphospholipid syndrome , autoimmune thyroiditis , and autoimmune hepatitis . These associations lend support to the concept that IGDA is a manifestation of an autoimmune etiology. In addition, IGDA has been described in association with pulmonary coccidioidomycosis , pulmonary silicosis , acute promyelocytic leukemia , chronic uveitis , and as a paraneoplastic process in association with bronchial squamous-cell carcinoma . Interstitial granulomatous dermatitis also has been reported in association with the consumption of soy  as well as with an herbal medication of unknown composition .
Drug-associated presentations have been described in conjunction with angiotensin-converting-enzyme inhibitors , calcium-channel blockers, beta-blockers, lipid-lowering agents , tumor necrosis factor-α blockers , and sennoside . Drug-associated interstitial granulomatous dermatitis is thought by some , but not all , to be distinguishable from IGDA histopathologically by the presence of vacuolar interface changes and/or epidermotropic lymphocytes. Other features thought to distinguish interstitial granulomatous drug reaction from IGDA include the presence of thick collagen bundles coated with the nuclear debris of neutrophils or eosinophilic granules, so-called flame figures , or the absence of neutrophils .
Treatments for IGDA are not well defined. Resolution of IGDA has been documented after treatment with systemic glucocorticoids [3, 13, 28], topical glucocorticoids , systemic and topical glucocorticoids together , nonsteroidal anti-inflammatory agents and topical glucocorticoids together , and infliximab . Of note, spontaneous resolution  as well as treatment resistant forms  have been described.
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