Abstract
Besides being an uncommon clinicopathological entity, interstitial granulomatous dermatitis, also described as interstitial granulomatous dermatitis with arthritis (IGDA), has shown a wide spectrum of clinical manifestations, such as linear and erythematous lesions, papules, plaques and nodules. Histological features include dense dermal histiocytic infiltrate, usually in a palisade configuration, and scattered neutrophils and eosinophils. We describe a middle aged woman with rheumatoid arthritis of difficult management and cutaneous lesions compatible with IGDA.
Keywords:
Rheumatoid arthritis; Dermatitis; Granuloma
INTRODUCTION
Interstitial granulomatous dermatitis was initially described by Ackerman et al in 1993.11 Ackerman A. Clues to Diagnosis in Dermatopathology. Chicago IL: ASCP Press;1993. p. 309-12. It is an infrequent dermatosis, more common in women with a previous diagnosis of rheumatoid arthritis (RA).22 Marmon S, Robinson M, Meehan SA, Franks AG Jr. Lupus-erythematous associated interstitial granulomatous dermatitis. Dermatol Online J. 2012;18:31.
Its clinical manifestations are variable. Classically it presents itself as linear
subcutaneous cords, known as rope sign.11 Ackerman A. Clues to Diagnosis in Dermatopathology. Chicago IL: ASCP
Press;1993. p. 309-12. Other
clinical forms were reported such as papules, subcutaneous plaques, annular lesions or
nodules, predominantly in lateral walls of thorax, abdomen and medial surface of
thighs.22 Marmon S, Robinson M, Meehan SA, Franks AG Jr. Lupus-erythematous
associated interstitial granulomatous dermatitis. Dermatol Online J.
2012;18:31.
3 Jabbari A, Cheung W, Kamino H, Soter NA. Interstitial granulomatous
dermatitis with arthritis. Dermatol Online J. 2009;15:22.-44 Sayah A, English JC. Rheumatoid arthritis: A review of the cutaneous
manifestations. J Am Acad Dermatol. 2005;53:191-209. Lesions are usually asymptomatic.55 Antunes J, Pacheco D, Travassos AR, Soares-Almeida LM, Filipe P,
Sacramento-Marques M. Autoimmune thyroiditis presenting as interstitial granulomatous
dermatitis. An Bras Dermatol. 2012;87:748-51.
At the histopathological examination, infiltration of reticular dermis was observed with predominance of interstitial and palisaded histiocytes and some areas of collagenous degeneration, associated with a lower number of neutrophils and eosinophils.66 Serra S, Monteiro P, Pires E, Vieira R, Telechea O, Inês L, et al. Relapsing polychondritis, interstitial granulomatous dermatitis and antiphospholipid syndrome: an unusual clinical association. Acta Reumatol Port. 2011;36:292-7.
The main associated disease is RA, which may be diagnosed before, concomitantly or after
the onset of lesions.55 Antunes J, Pacheco D, Travassos AR, Soares-Almeida LM, Filipe P,
Sacramento-Marques M. Autoimmune thyroiditis presenting as interstitial granulomatous
dermatitis. An Bras Dermatol. 2012;87:748-51. There are reports of
association with several diseases, besides medication, especially antihypertensive
drugs.22 Marmon S, Robinson M, Meehan SA, Franks AG Jr. Lupus-erythematous
associated interstitial granulomatous dermatitis. Dermatol Online J.
2012;18:31.
3 Jabbari A, Cheung W, Kamino H, Soter NA. Interstitial granulomatous
dermatitis with arthritis. Dermatol Online J. 2009;15:22.
4 Sayah A, English JC. Rheumatoid arthritis: A review of the cutaneous
manifestations. J Am Acad Dermatol. 2005;53:191-209.
5 Antunes J, Pacheco D, Travassos AR, Soares-Almeida LM, Filipe P,
Sacramento-Marques M. Autoimmune thyroiditis presenting as interstitial granulomatous
dermatitis. An Bras Dermatol. 2012;87:748-51.-66 Serra S, Monteiro P, Pires E, Vieira R, Telechea O, Inês L, et al.
Relapsing polychondritis, interstitial granulomatous dermatitis and antiphospholipid
syndrome: an unusual clinical association. Acta Reumatol Port.
2011;36:292-7. In these cases, a more peculiar histopathological picture was
observed, with vacuolar interface dermatitis.33 Jabbari A, Cheung W, Kamino H, Soter NA. Interstitial granulomatous
dermatitis with arthritis. Dermatol Online J. 2009;15:22.
CASE REPORT
Female patient, 52 years old, came to the dermatological ambulatory with a two-month history of plaques and grouped nodules, erythematous-purplish, some infi ltrates with annular confi guration and symmetric distribution on medial surface of thighs, associated with erythematous papules on the left elbow with local pruritus (Figures 1 and 2).
Right thigh. Papules, annular plaques and erythematous-purplish infiltrated nodules on medial surface of right thigh
Left thigh. Papules, annular plaques and erythematous-purplish infiltrated nodules on medial surface of left thigh
Pathological history: RA, diagnosed 10 years ago with symmetrical deforming polyarthritis of the small-joints of hands and being monitored by the Rheumatology Service of HSPE-SP; systemic arterial hypertension and obesity. She was using: prednisone 5mg/day, methotrexate 7.5 mg/week, losartan 50 mg/day, fluoxetine 20 mg/day, acetaminophen and naproxen sporadically, in case of joint pain.
Laboratory tests: rheumatoid factor present at high titers on the occasion of rheumatoid arthritis diagnosis, anti-cyclic citrullinated peptide antibodies present, increased inflammatory markers, without alterations in other tests.
The patient was submitted to incisional biopsy of skin and the histopathological study revealed interstitial granulomatous dermatitis, without evidence of vacuolar interface dermatitis on both thighs and elbow lesions (Figures 3 to 6).
Elbow lesion. Detail of interstitial granulomatous infiltrate amid thickened collagen. HEAO 200x
Thigh lesion. Detail of infiltrate with histiocytes, lymphocytes, eosinophils and neutrophils amid thickened collagen. HEAO 400x
Elbow lesion. Normal epidermis for this site, without basal cell vacuolar degeneration. Dermis with moderate infiltrate predominantly histiocytic amid deteriorated and thickened collagen. HEAO 100x
DISCUSSION
IGDA is a rare dermatosis, initially described by Ackerman et al as Ackerman syndrome, in 1993.11 Ackerman A. Clues to Diagnosis in Dermatopathology. Chicago IL: ASCP Press;1993. p. 309-12.
Although the original manifestation had been described as subcutaneous linear nodules,
also known as rope sign11 Ackerman A. Clues to Diagnosis in Dermatopathology. Chicago IL: ASCP
Press;1993. p. 309-12., later reports showed a
clinical spectrum quite heterogeneous which vary from hyperpigmented, erythematous
papules, subcutaneous plaques, annular lesions to firm red-purplish nodules as observed
in our patient.22 Marmon S, Robinson M, Meehan SA, Franks AG Jr. Lupus-erythematous
associated interstitial granulomatous dermatitis. Dermatol Online J.
2012;18:31.
3 Jabbari A, Cheung W, Kamino H, Soter NA. Interstitial granulomatous
dermatitis with arthritis. Dermatol Online J. 2009;15:22.-44 Sayah A, English JC. Rheumatoid arthritis: A review of the cutaneous
manifestations. J Am Acad Dermatol. 2005;53:191-209. The lesions are usually asymptomatic, but can be slightly pruritic
or painful.55 Antunes J, Pacheco D, Travassos AR, Soares-Almeida LM, Filipe P,
Sacramento-Marques M. Autoimmune thyroiditis presenting as interstitial granulomatous
dermatitis. An Bras Dermatol. 2012;87:748-51.
The histopathological examination defines the diagnosis characterized as dense and diffuse interstitial infiltrate in the reticular dermis, composed of histiocytes in a palisade arrangement, sometimes with necrobiosis of collagen and involved by some neutrophils and eosinophils.66 Serra S, Monteiro P, Pires E, Vieira R, Telechea O, Inês L, et al. Relapsing polychondritis, interstitial granulomatous dermatitis and antiphospholipid syndrome: an unusual clinical association. Acta Reumatol Port. 2011;36:292-7. Usually there are deposits of mucin and absence of vasculitis.22 Marmon S, Robinson M, Meehan SA, Franks AG Jr. Lupus-erythematous associated interstitial granulomatous dermatitis. Dermatol Online J. 2012;18:31.,77 Felcht M, Faulhaber J, Göttmann U, Koenen W, Goerdt S, Goebeler M. Interstitial granulomatous dermatitis (Ackerman's Syndrome). Eur J Dermatol. 2010;20:661-2. This last characteristic is useful in distinguishing it from another uncommon disease and has been reported several times in patients with RA, the palisaded neutrophilic granulomatous dermatitis. It is histopathologically characterized for affecting all the dermis, differently from IGDA, which is located in the middle and deep dermis and demonstrates an infiltrate rich in neutrophils, with vascular alterations and leukocytoclasia.
Its physiopathology is uncertain, however the association with autoimmune diseases and
vasculitides suggests a mechanism mediated by immunocomplexes.55 Antunes J, Pacheco D, Travassos AR, Soares-Almeida LM, Filipe P,
Sacramento-Marques M. Autoimmune thyroiditis presenting as interstitial granulomatous
dermatitis. An Bras Dermatol. 2012;87:748-51.,66 Serra S, Monteiro P, Pires E, Vieira R, Telechea O, Inês L, et al.
Relapsing polychondritis, interstitial granulomatous dermatitis and antiphospholipid
syndrome: an unusual clinical association. Acta Reumatol Port.
2011;36:292-7. Interstitial
granulomatous dermatitis is more commonly described in women with a previous diagnosis
of RA, such as the present case.22 Marmon S, Robinson M, Meehan SA, Franks AG Jr. Lupus-erythematous
associated interstitial granulomatous dermatitis. Dermatol Online J.
2012;18:31.,55 Antunes J, Pacheco D, Travassos AR, Soares-Almeida LM, Filipe P,
Sacramento-Marques M. Autoimmune thyroiditis presenting as interstitial granulomatous
dermatitis. An Bras Dermatol. 2012;87:748-51. Other associated
diseases already reported in the literature include systemic lupus erythematosus,
antiphospholipid syndrome, autoimmune thyroiditis and autoimmune hepatitis,
Churg-Strauss syndrome, Behcet's disease, pulmonary paracoccidioidomycosis, pulmonary
silicosis, chronic uveitis, promyelocytic leukemia and even bronchial and esophageal
squamous cell carcinomas such as paraneoplastic syndrome.22 Marmon S, Robinson M, Meehan SA, Franks AG Jr. Lupus-erythematous
associated interstitial granulomatous dermatitis. Dermatol Online J.
2012;18:31.
3 Jabbari A, Cheung W, Kamino H, Soter NA. Interstitial granulomatous
dermatitis with arthritis. Dermatol Online J. 2009;15:22.
4 Sayah A, English JC. Rheumatoid arthritis: A review of the cutaneous
manifestations. J Am Acad Dermatol. 2005;53:191-209.
5 Antunes J, Pacheco D, Travassos AR, Soares-Almeida LM, Filipe P,
Sacramento-Marques M. Autoimmune thyroiditis presenting as interstitial granulomatous
dermatitis. An Bras Dermatol. 2012;87:748-51.-66 Serra S, Monteiro P, Pires E, Vieira R, Telechea O, Inês L, et al.
Relapsing polychondritis, interstitial granulomatous dermatitis and antiphospholipid
syndrome: an unusual clinical association. Acta Reumatol Port.
2011;36:292-7.
Pharmacological etiology has also been reported and the most frequently drugs involved are the antihypertensives, such as the angiotensin-converting-enzyme inhibitors, calcium channel blockers, beta blockers, diuretics, in addition to hypolipidemic agents, anticonvulsants, antihistamines and TNF-alpha blockers.33 Jabbari A, Cheung W, Kamino H, Soter NA. Interstitial granulomatous dermatitis with arthritis. Dermatol Online J. 2009;15:22.,44 Sayah A, English JC. Rheumatoid arthritis: A review of the cutaneous manifestations. J Am Acad Dermatol. 2005;53:191-209.,66 Serra S, Monteiro P, Pires E, Vieira R, Telechea O, Inês L, et al. Relapsing polychondritis, interstitial granulomatous dermatitis and antiphospholipid syndrome: an unusual clinical association. Acta Reumatol Port. 2011;36:292-7.,77 Felcht M, Faulhaber J, Göttmann U, Koenen W, Goerdt S, Goebeler M. Interstitial granulomatous dermatitis (Ackerman's Syndrome). Eur J Dermatol. 2010;20:661-2. In these cases, the histopathological examination is commonly differentiated with vacuolar degenerative changes, exocytosis of lymphocytes and absence of neutrophils.33 Jabbari A, Cheung W, Kamino H, Soter NA. Interstitial granulomatous dermatitis with arthritis. Dermatol Online J. 2009;15:22. The absence of vacuolar interface dermatitis and the fact that the patient had suspended all medication for six months based on her own decision, with persistent IGDA lesions, speak against this cause.
Differential diagnosis includes other entities related to rheumatoid arthritis, such as rheumatoid nodules, rheumatoid vasculitis, palisaded neutrophilic and granulomatous dermatitis, in addition to rheumatoid neutrophilic dermatosis, which, unlike the latter, presents neutrophilic dermal infiltrate and leukocytoclasia without vasculitis under histopathology.88 Mashek HA, Pham CT, Helm TN, Klaus M. Rheumatoid Neutrophilic Dermatitis. Arch Dermatol. 1997;133:757-60. Lichen planus, erythema multiforme, erythema elevatum diutinum44 Sayah A, English JC. Rheumatoid arthritis: A review of the cutaneous manifestations. J Am Acad Dermatol. 2005;53:191-209. and granuloma annulare must also be considered, for it is considered a variant of the latter.99 Romiti R, Sakai N. Dermatite intersticial granulomatosa com artrite. Variante do granuloma anular? An Bras Dermatol. 1999;74:149-52.
The therapy of choice is still not well-defined.22 Marmon S, Robinson M, Meehan SA, Franks AG Jr. Lupus-erythematous
associated interstitial granulomatous dermatitis. Dermatol Online J.
2012;18:31.-33 Jabbari A, Cheung W, Kamino H, Soter NA. Interstitial granulomatous
dermatitis with arthritis. Dermatol Online J. 2009;15:22.,55 Antunes J, Pacheco D, Travassos AR, Soares-Almeida LM, Filipe P,
Sacramento-Marques M. Autoimmune thyroiditis presenting as interstitial granulomatous
dermatitis. An Bras Dermatol. 2012;87:748-51.
6 Serra S, Monteiro P, Pires E, Vieira R, Telechea O, Inês L, et al.
Relapsing polychondritis, interstitial granulomatous dermatitis and antiphospholipid
syndrome: an unusual clinical association. Acta Reumatol Port.
2011;36:292-7.-77 Felcht M, Faulhaber J, Göttmann U, Koenen W, Goerdt S, Goebeler M.
Interstitial granulomatous dermatitis (Ackerman's Syndrome). Eur J Dermatol.
2010;20:661-2. Different treatments have been reported in literature with different
degrees of success, ranging from topical or systemic corticosteroids,
anti-inflammatories, methotrexate, hydroxychloroquine, amid others.33 Jabbari A, Cheung W, Kamino H, Soter NA. Interstitial granulomatous
dermatitis with arthritis. Dermatol Online J. 2009;15:22.
4 Sayah A, English JC. Rheumatoid arthritis: A review of the cutaneous
manifestations. J Am Acad Dermatol. 2005;53:191-209.
5 Antunes J, Pacheco D, Travassos AR, Soares-Almeida LM, Filipe P,
Sacramento-Marques M. Autoimmune thyroiditis presenting as interstitial granulomatous
dermatitis. An Bras Dermatol. 2012;87:748-51.
6 Serra S, Monteiro P, Pires E, Vieira R, Telechea O, Inês L, et al.
Relapsing polychondritis, interstitial granulomatous dermatitis and antiphospholipid
syndrome: an unusual clinical association. Acta Reumatol Port.
2011;36:292-7.-77 Felcht M, Faulhaber J, Göttmann U, Koenen W, Goerdt S, Goebeler M.
Interstitial granulomatous dermatitis (Ackerman's Syndrome). Eur J Dermatol.
2010;20:661-2. A spontaneous
resolution my also occur in weeks to months, with surges and relapses.33 Jabbari A, Cheung W, Kamino H, Soter NA. Interstitial granulomatous
dermatitis with arthritis. Dermatol Online J. 2009;15:22.,55 Antunes J, Pacheco D, Travassos AR, Soares-Almeida LM, Filipe P,
Sacramento-Marques M. Autoimmune thyroiditis presenting as interstitial granulomatous
dermatitis. An Bras Dermatol. 2012;87:748-51.-66 Serra S, Monteiro P, Pires E, Vieira R, Telechea O, Inês L, et al.
Relapsing polychondritis, interstitial granulomatous dermatitis and antiphospholipid
syndrome: an unusual clinical association. Acta Reumatol Port.
2011;36:292-7.
Considering IGDA as a rare entity, the knowledge of its manifestations and its essential association with rheumatoid arthritis contributes to clinical suspicion, since its wide spectrum presentation makes its diagnosis difficult. Dermatologists should be alert to this diagnostic possibility, for they are already in a privileged position when monitoring these patients.
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Financial Support: None.
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How to cite this article: Veronez IS, Dantas FL, Valente NY, Kakizaki P, Yasuda TH, Cunha TA. Interstitial granulomatous dermatitis: rare cutaneous manifestation of rheumatoid arthritis. An Bras Dermatol. 2015; 90(3):391-3.
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*
Work performed at Serviço de Dermatologia do Hospital do Servidor Público Estadual de São Paulo – São Paulo (SP), Brazil.
Reference
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1Ackerman A. Clues to Diagnosis in Dermatopathology. Chicago IL: ASCP Press;1993. p. 309-12.
-
2Marmon S, Robinson M, Meehan SA, Franks AG Jr. Lupus-erythematous associated interstitial granulomatous dermatitis. Dermatol Online J. 2012;18:31.
-
3Jabbari A, Cheung W, Kamino H, Soter NA. Interstitial granulomatous dermatitis with arthritis. Dermatol Online J. 2009;15:22.
-
4Sayah A, English JC. Rheumatoid arthritis: A review of the cutaneous manifestations. J Am Acad Dermatol. 2005;53:191-209.
-
5Antunes J, Pacheco D, Travassos AR, Soares-Almeida LM, Filipe P, Sacramento-Marques M. Autoimmune thyroiditis presenting as interstitial granulomatous dermatitis. An Bras Dermatol. 2012;87:748-51.
-
6Serra S, Monteiro P, Pires E, Vieira R, Telechea O, Inês L, et al. Relapsing polychondritis, interstitial granulomatous dermatitis and antiphospholipid syndrome: an unusual clinical association. Acta Reumatol Port. 2011;36:292-7.
-
7Felcht M, Faulhaber J, Göttmann U, Koenen W, Goerdt S, Goebeler M. Interstitial granulomatous dermatitis (Ackerman's Syndrome). Eur J Dermatol. 2010;20:661-2.
-
8Mashek HA, Pham CT, Helm TN, Klaus M. Rheumatoid Neutrophilic Dermatitis. Arch Dermatol. 1997;133:757-60.
-
9Romiti R, Sakai N. Dermatite intersticial granulomatosa com artrite. Variante do granuloma anular? An Bras Dermatol. 1999;74:149-52.
Publication Dates
-
Publication in this collection
June 2015
History
-
Received
12 Nov 2013 -
Accepted
27 Nov 2013