—  SPECIALTY CONFERENCE  —

Dermatopathology

Case 8 - Interstitial Granulomatous Dermatitis (IGD) with Sero-Negative Arthritis

J. Andrew Carlson
Albany Medical College
Albany, NY


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Patient
40yo female. Asymptomatic truncal rash.

Clinical impression
granuloma annulare/rheumatoid nodule.

Diagnosis
Interstitial granulomatous dermatitis (IGD) with sero-negative arthritis

Clinicopathologic findings

Clinical History
40yo female with sero-negative arthritis presented with annular and cord-like configurations (rope sign) of asymptomatic papules and plaques affecting the trunk, mostly the flanks. Clinical diagnosis: granuloma annulare or rheumatoid nodule. She had no recent change in medications and her current therapeutic regime included methotrexate, prednisone, Vioxx™((rofecoxib), Arava™(leflunomide), and Remicade™(infliximab). Apart from the cutaneous eruption, she feels well and is without complaint. Serology is negative for rheumatoid factor, but positive for anti-nuclear antibodies (ANA).


Case 8 - Figure 1 - There are cord-like cutaneous lesions with plaques on the trunk.
Case 8 - Figure 2 - There is a mid- and deep-dermal perivascular and interstitial mononuclear cell infiltrate.
Case 8 - Figure 3 - There is a mid- and deep-dermal perivascular and interstitial mononuclear cell infiltrate.


Case 8 - Figure 4 - The infiltrate comprises interstitial histiocytes associated with necrosis of collagen bundles.
Case 8 - Figure 5 - The infiltrate comprises interstitial histiocytes associated with necrosis of collagen bundles.
Case 8 - Figure 6 - The infiltrate comprises interstitial histiocytes associated with necrosis of collagen bundles.


Case 8 - Figure 7 - CD68 - The infiltrate comprises CD68-expressing histiocytes.
Case 8 - Figure 8 - IgG - There is IgG deposition in the dermis around collagen fibres.

Histologic findings
The mid and deep dermis contains nodular aggregates of macrophages admixed with numerous eosinophils. In addition, there are palisaded granulomas surrounding foci of degenerated collagen bundles as well as flame figures . No evidence of vasculitis (vessel wall disruption, fibrin depostis or nuclear debris- leukocytoclasia), interface dermatitis, mucin deposits, nor lymphocytic perivasculitis were found.

Direct immunofluorescence findings
Deep dermal, interstitial IgG, C3 and IgM deposits coating collagen bundles and IgG antinuclear keratinocyte reactivity were evident. No vascular or basement membrane zone immunoreactants were identified.

Discussion
IGD with arthritis (a.k.a. Ackerman syndrome) is a distinctive, rare entity affecting mostly women that is characterized clinically by cords or plaques affecting the trunk and proximal extremities and is typically associated with seronegative arthritis-rheumatoid polyarthralgia. This was first described as a distinct entity by Ackerman et al [1, 2] . In addition to sero-negative and sero-positive rheumatoid arthritis [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12] , other disease associations have been identified in association with IGD that include drug reactions [13, 14, 15, 16] , other autoimmune diseases- systemic lupus erythematosus [3, 17, 18, 19] and thyroiditis [3, 14] , chronic infections [20, 21] , silicosis [22] , and paraneoplastic syndrome [23] .

Clinical findings
Clinical lesions are large erythematous, symmetrically distributed plaques affecting the upper trunk and flank, abdomen and inner thighs. Often these lesions have a cord-like morphology, "the rope sign", which radiate from the axillae down the patient's flank. These cords or plaques are typically asymptomatic or burn slightly. Most affected patients are females who invariably have rheumatoid symptoms and frequently have serologic findings (auto-antibodies) and other evidence of systemic autoimmune disorders. Most will have an elevated erythrocyte sedimentation rate (ESR) and over half will show one or more auto-antibodies. This patient had skin lesions corresponding to the rope sign and as noted in other reports where cords where present, was rheumatoid factor-, but ANA+ ,and had symmetric, non-erosive arthritis.

Pathologic findings
The histologic pattern found in IGD with sero-negative arthritis appears to be predictive of the clinical appearance that is characterized by large erythematous plaques or cords, symmetrically distributed, mostly in skin folds. Interstitial infiltrates of macrophages in mid and deep dermis that can show palisades around degenerated collagen (necrobiotic) bundles. Variable numbers of eosinophils and neutrophils are present, most often situated around zones of degenerated collagen bundles. Flame figures have been also reported in this setting.

Classification
Some authors include this disorder in the spectrum of palisaded neutrophilic granulomatous dermatitis of immune complex disease (i.e. Churg Strauss granulomas, rheumatoid papules, Winkelmann's granuloma, cutaneous extravascular necrotizing granuloma [5, 24, 25, 26] }; however, small vessel vasculitis has not been described in IGD with arthritis nor do these lesions contain significant infiltrates of neutrophils or eosinophils as typically found in palisading neutrophilic and granulomatous dermatitis [5, 27] .

Pathogenesis
Circulating immune complexes [6, 19] or altered apoptosis have been discussed as mechanisms, but no experimental evidence exists to support either hypothesis.

Differential diagnosis

Necrobiosis lipoidica
Interstital granulomatous drug eruption
Granulomatous mycosis fungoides
Leukemia cutis, myelogenous type
Methotrexate induced papular eruption in patients with rheumatic disease [28]

Conclusion
IGD presenting as plaques or cords is a distinct entity with highly reproducible clinical and pathologic features. Its recognition is important to signal to the treating clinicians of the possibility of an underlying systemic disorder such as an autoimmune disease.

References

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