Case 8 -
Interstitial Granulomatous Dermatitis (IGD) with Sero-Negative
J. Andrew Carlson
Albany Medical College
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40yo female. Asymptomatic truncal rash.
Interstitial granulomatous dermatitis (IGD) with sero-negative
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.
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.
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
. In addition to sero-negative and sero-positive rheumatoid
, other disease associations have been identified in association with IGD that include
, other autoimmune diseases- systemic lupus erythematosus
, chronic infections
, silicosis  , and paraneoplastic syndrome  .
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,
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.
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
}; 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
Circulating immune complexes
or altered apoptosis have been discussed as mechanisms, but no experimental evidence exists to support
|Interstital granulomatous drug eruption|
|Granulomatous mycosis fungoides|
|Leukemia cutis, myelogenous type|
|Methotrexate induced papular eruption in patients with rheumatic disease |
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.
- Ackerman A, White WL, Guo Y, Umbert I. Granuloma annulare, interstitial type vs. interstitial granulomaous dermatitis with arthritis. In: Differential diagnosis in dermatopathology IV. Philadelphia: Lea & Febiger; 1994. p. 34-7.
- Gottlieb G, Duve R, Ackerman A. Interstitial granulomatous dermatitis with cutaneous cords and arthritis: linear subcutaneous bands in rheumatoid arthritis revisited. Dermatopathol: Pract and Conc 1995;1:3-6.
- Tomasini C, Pippione M. Interstitial granulomatous dermatitis with plaques. J Am Acad Dermatol 2002;46(6):892-9.
- Banuls J, Betlloch I, Botella R, Jimenez MJ, Blanes M, Pascual JC, et al. Interstitial granulomatous dermatitis with plaques and arthritis. Eur J Dermatol 2003;13(3):308-10.
- Sangueza OP, Caudell MD, Mengesha YM, Davis LS, Barnes CJ, Griffin JE, et al. Palisaded neutrophilic granulomatous dermatitis in rheumatoid arthritis. J Am Acad Dermatol 2002;47(2):251-7.
- Ebschner U, Hartschuh W, Petzoldt D. [Interstitial granulomatous dermatitis with arthritis]. Hautarzt 2000;51(2):90-4.
- Long D, Thiboutot DM, Majeski JT, Vasily DB, Helm KF. Interstitial granulomatous dermatitis with arthritis. J Am Acad Dermatol 1996;34(6):957-61.
- Dykman CJ, Galens GJ, Good AE. Linear Subcutaneous Bands in Rheumatoid Arthritis. An Unusual Form of Rheumatoid Granuloma. Ann Intern Med 1965;63:134-40.
- McDow RA, Fields JP. Linear granuloma annulare of the finger. Cutis 1987;39(1):43-4.
- Betlloch I, Moragon M, Jorda E, Jimenez A, Ramon D, Verdeguer JM. Linear rheumatoid nodule. Int J Dermatol 1988;27(9):645-6.
- Harpster EF, Mauro T, Barr RJ. Linear granuloma annulare. J Am Acad Dermatol 1989;21(5 Pt 2):1138-41.
- Tomasini C, Aloi F. Correction: interstitial granulomaotus dermatitis with cutaneous cords and arthritis: "railway track dermatitis" revisited. Dermatopathol: Pract and Conc 1998;4(4):316-19.
- Magro CM, Crowson AN, Schapiro BL. The interstitial granulomatous drug reaction: a distinctive clinical and pathological entity. J Cutan Pathol 1998;25(2):72-8.
- Aloi F, Tomasini C, Pippione M. Interstitial granulomatous dermatitis with plaques. Am J Dermatopathol 1999;21(4):320-3.
- Lee MW, Choi JH, Sung KJ, Moon KC, Koh JK. Interstitial and granulomatous drug reaction presenting as erythema nodosum-like lesions. Acta Derm Venereol 2002;82(6):473-4.
- Perrin C, Lacour JP, Castanet J, Michiels JF. Interstitial granulomatous drug reaction with a histological pattern of interstitial granulomatous dermatitis. Am J Dermatopathol 2001;23(4):295-8.
- Chu P, Connolly MK, LeBoit PE. The histopathologic spectrum of palisaded neutrophilic and granulomatous dermatitis in patients with collagen vascular disease. Arch Dermatol 1994;130(10):1278-83.
- Obermoser G, Zelger B, Zangerle R, Sepp N. Extravascular necrotizing palisaded granulomas as the presenting skin sign of systemic lupus erythematosus. Br J Dermatol 2002;147(2):371-4.
- Verneuil L, Dompmartin A, Comoz F, Pasquier CJ, Leroy D. Interstitial granulomatous dermatitis with cutaneous cords and arthritis: a disorder associated with autoantibodies. J Am Acad Dermatol 2001;45(2):286-91.
- Moreno C, Kutzner H, Palmedo G, Goerttler E, Carrasco L, Requena L. Interstitial granulomatous dermatitis with histiocytic pseudorosettes: a new histopathologic pattern in cutaneous borreliosis. Detection of Borrelia burgdorferi DNA sequences by a highly sensitive PCR-ELISA. J Am Acad Dermatol 2003;48(3):376-84.
- DiCaudo DJ, Connolly SM. Interstitial granulomatous dermatitis associated with pulmonary coccidioidomycosis. J Am Acad Dermatol 2001;45(6):840-5.
- Kroesen S, Itin PH, Hasler P. Arthritis and interstitial granulomatous dermatitis (Ackerman syndrome) with pulmonary silicosis. Semin Arthritis Rheum 2003;32(5):334-40.
- Schreckenberg C, Asch PH, Sibilia J, Walter S, Lipsker D, Heid E, et al. [Interstitial granulomatous dermatitis and paraneoplastic rheumatoid polyarthritis disclosing cancer of the lung]. Ann Dermatol Venereol 1998;125(9):585-8.
- Finan MC, Winkelmann RK. The cutaneous extravascular necrotizing granuloma (Churg-Strauss granuloma) and systemic disease: a review of 27 cases. Medicine (Baltimore) 1983;62(3):142-58.
- Dicken CH, Winkelmann RK. The Churg-Strauss granuloma: cutaneous, necrotizing, palisading granuloma in vasculitis syndromes. Arch Pathol Lab Med 1978;102(11):576-80.
- Wilmoth GJ, Perniciaro C. Cutaneous extravascular necrotizing granuloma (Winkelmann granuloma): confirmation of the association with systemic disease. J Am Acad Dermatol 1996;34(5 Pt 1):753-9.
- Drage LA, Davis MD, De Castro F, Van Keulen V, Weiss EA, Gleich GJ, et al. Evidence for pathogenic involvementof eosinophils and neutrophilsin Churg-Strauss syndrome. J Am Acad Dermatol 2002;47(2):209-16.
- Goerttler E, Kutzner H, Peter HH, Requena L. Methotrexate-induced papular eruption in patients with rheumatic diseases: a distinctive adverse cutaneous reaction produced by methotrexate in patients with collagen vascular diseases. J Am Acad Dermatol 1999;40(5 Pt 1):702-7.