Dermatology Online Journal

Interstitial granulomatous dermatitis
Hillary Johnson MD PhD, Stephanie Mengden MD, Ronald R Brancaccio MD
Dermatology Online Journal 14 (5): 18

Department of Dermatology, New York University

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Abstract

A 59-year-old woman with arthritis presented to the Skin Institute of New York with a 2-month history of asymptomatic, small, skin-colored papules that erupted symmetrically on the chest, back, and proximal extremities. Histopathologic examination of a biopsy specimen showed findings of interstitial granulomatous dermatitis. Clinical correlation suggested a diagnosis of interstitial granulomatous dermatitis with arthritis. No change in the lesions resulted from application of clobetasol 0.05 percent ointment to the affected areas.

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Clinical synopsis

A 59-year-old woman presented to the Skin Institute of New York in August 2006 with a 2-month history of numerous, skin-colored, small papules that were distributed symmetrically on the proximal aspects of the extremities and upper trunk. They were not pruritic or painful. The non-remitting lesions began suddenly and preceded a flare in joint pain. Medical history included rheumatoid-factor-negative arthritis that previously had been treated with non-steroidal anti-inflammatory medications and gold therapy, chronic obstructive pulmonary disease, and emphysema. Tobacco use had been discontinued for 5 years. No family history of skin disorders was reported. The patient denied recent travel or any new illness. Her medications included alprazolam and atorvastatin, which she has taken for 4 years. Metaxalone, which is a centrally acting skeletal muscle relaxant, had been started 5 months earlier. The patient also had been on vitamin B12, folate, and calcium carbonate supplements on a long-term basis. A punch biopsy was performed of a representative papule from the left axilla. The patient had received no previous treatment or topical medications. To date, treatment with topical clobetasol 0.05 percent ointment has not resulted in change in the lesion number or character.

Physical examination

Numerous, discrete, monomorphic, skin-colored papules were scattered in a symmetric pattern on the upper chest, posterior upper shoulders, posterior neck, and proximal extremities. On the extremities, the papules were arranged on the posterior upper arms, which included the axillary vaults, and superior medial thighs.

Figure 1	Figure 2

Laboratory data

A complete blood count, erythrocyte sedimentation rate, comprehensive metabolic panel, fasting lipid panel, and C-reactive protein were normal. Anti-nuclear and Sjogren single-stranded A and B antibodies and rheumatoid factor were negative

Histopathology

Throughout the dermis, there is an interstitial infiltrate of histiocytes, lymphocytes, and eosinophils. A colloidal iron stain shows increased deposition of mucin. A Periodic acid-Schiff and diastase stain fails to show a thick basement membrane or evidence of fungi.

Comment

Interstitial granulomatous dermatitis (IGD) is a histologic inflammatory reaction pattern with a large differential diagnosis that requires clinicopathologic correlation to identify the underlying cause. Interstitial granulomatous dermatitis is typically associated with autoimmune or connective-tissue disorders; such as rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, and lymphoproliferative disorders [1-7]. It may also be induced by systemic medication. First described in 1993, interstitial granulomatous dermatitis with arthritis (IGDA) is an uncommon form of interstitial granulomatous dermatitis that often occurs in women with rheumatoid factor positive or seronegative arthritis. Other autoantibodies or an elevated erythrocyte sedimentation rate may or may not develop [8, 9-16]. The clinical presentation in IGDA was initially described as nontender, erythematous plaques that affected the trunk and extremities. In some cases, the plaques form palpable cord-like lesions, which is termed the rope sign, which is no longer considered pathognomonic for IGDA and may not be observed in all cases. The cutaneous clinical presentation is variable in spectrum and features papules to annular or linear plaques. Lesions are asymptomatic and often symmetrically distributed. Arthralgias and myalgias may occur before, after, or during the onset of the skin lesions [9-16]. Histopathologic classification of IGDA is controversial. Interstitial granulomatous dermatitis is considered by some to be a unique diagnostic entity because it has never been reported to involve leukocytoclastic vasculitis, and histopathologic features have not been shown to vary greatly over time [9-16]. Others, however, propose that IGDA represents a subgroup variant of palisaded neutrophilic and granulomatous dermatitis (PNGD), which is a spectrum of disorders that involve degeneration of collagen postulated to be immune complex-mediated. Rheumatoid arthritis and other collagen vascular or autoimmune diseases have been reported to occur concurrently with PNGD. In PNGD, early lesions involve a neutrophilic infiltrate with leukocytoclastic vasculitis. Older lesions tend to show a palisaded granulomatous infiltrate that surrounds centralized or scattered neutrophils and less commonly eosinophils nearby degenerated collagen [1, 17, 18]. In IGDA, the dense dermal lymphohistiocytic infiltrate usually extends throughout the reticular dermis in contrast to granuloma annulare. Histiocytes can potentially form rosettes around degenerating collagen. In contrast to PNGD, the presence of neutrophils, mucin deposition, and signs of leukocytic vasculitis are not seen [9-16]. Differential diagnosis of interstitial granulomatous dermatitis with arthritis includes granuloma annulare, urticarial vasculitis, erythema chronicum migrans (Lyme borreliosis), rheumatoid neutrophilic dermatosis, mycosis fungoides (granulomatous slack skin), necrobiosis lipoidica, and granulomatous drug reactions. Implicated drugs include calcium channel blockers, angiotensin-converting enzyme inhibitors, beta-blockers, lipid lowering agents, antihistamines, anticonvulsants, antidepressants, sennosides, and tumor necrosis factor alpha inhibitors (lenalidomide, infliximab, etanercept, and adalimumab) [19-21]. Clinicopathologic correlation in this patient with arthritis is suggestive of IGDA. Interestingly, prior case reports of IGDA have not included a clinical description fully matching the patient's nonerythematous, skin-colored, papular, symmetric cutaneous eruption. However, the clinical presentation in IGDA is considered variable. An atypical granulomatous drug reaction was considered in the differential diagnosis, but the medication history did not support this diagnosis. Cutaneous manifestations of allergy to metaxalone have not been reported in the literature. Likewise, long-term medications alprazolam, atorvastatin, and dietary supplements have not been reported to invoke insterstitial granulomatous dermatitis [22, 23].

References

1. Chu P, et al. The histopathologic spectrum of palisaded neutrophilic and granulomatous dermatitis in rheumatoid arthritis. Arch Dermatol 1994; 130:1278

2. Kroesen S, et al. Arthritis and interstitial granulomatous dermatitis (Ackerman syndrome) with pulmonary silicosis. Semin Arthritis Rheum 2003; 32:334

3. Lee M, et al. Interstitial granulomatous dermatitis with plaques associated with antiphospholipid syndrome. Br J Dermatol 2005; 152:803

4. DiCauido D, et al. Interstitial granulomatous dermatitis associated with pulmonary coccidiomycosis. J Am Acad Dermatol 2001; 45:840

5. Deng A, et al. Interstitial granulomatous dermatitis associated with the use of tumor necrosis factor alpha inhibitors. Arch Dermatol 2006; 142:198

6. Chen D, et al. A novel case of polyfibromatosis and interstitial granulomatous dermatitis with arthritis. J Am Acad Dermatol 2006; 55:S32

7. Dubey S., Merry P. Interstitial granulomatous dermatitis (Ackerman's syndrome) in SLE presenting with the "rope sign." Rheumatology Advance Access, published August 25, 2006. doi:10.1093/rheumatology/kel 264

8. Ackerman A, et al. Clues to diagnosis in dermatopathology. Chicago. ASCB Press, 1993:309

9. Tomasini C, Pippione M. Interstitial granulomatous dermatitis with plaques. J Am Acad Dermatol 2002; 46:892

10. Banuls J, et al. Interstitial granulomatous dermatitis with arthritis. Eur J Dermatol 2003; 13:308

11. Aloi F, et al. Interstitial granulomatous dermatitis with plaques. Am J Dermatopath 1999; 21:320

12. Long D, et al. Interstitial granulomatous dermatitis with arthritis. J Am Acad Dermatol 1996; 34:957

13. Wollina, U, et al. Interstitial granulomatous dermatitis with plaques and arthritis. Clin Rheumatol 2003; 22:347

14. Verneuil L, et al. Interstitial granulomatous dermatitis with cutaneous cords and arthritis. J Am Acad Dermatol 2001; 45:286

15. Crowson A, Magro C. Interstitial granulomatous dermatitis with arthritis. Human Pathol 2004; 35:79

16. Altaykan A, et al. Interstitial granulomatous dermatitis with arthritis. Human Pathol 2004; 35:892

17. Sangueza O, et al. Palisaded neutrophilic granulomatous dermatitis in rheumatoid arthritis. J Am Acad Dermatol 2002; 47:251

18. Mashek H, et al. Rheumatologic neutrophilic dermatitis. Arch Dermatol 1997; 113:757

19. Perrin C, et al. Interstitial granulomatous dermatitis drug reaction with a histological pattern of interstitial granulomatous dermatitis. Am J Dermatopathol 2001; 23:295

20. Magro C, et al. The interstitial granulomatous drug reactions: a distinctive clinical and pathological entity. J Cutan Pathol 1998; 25:72

21. Lee M, et al. Interstitial and granulomatous drug reaction presenting as erythema nodosum-like lesions. Acta Derm Venereol 2002; 82:473

22. Thomsom Micromedex; www.micromedex.com.

23. FDA Index to Drug Specific Information; www.fda.gov/cder/drug/DrugSafety/DrugIndex.htm

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