Hyperpigmented, hypertrichotic, and sclerodermoid plaques: An unusual variant of Muckle–Wells syndrome
2009; Elsevier BV; Volume: 61; Issue: 4 Linguagem: Inglês
10.1016/j.jaad.2009.03.020
ISSN1097-6787
Autores Tópico(s)Histiocytic Disorders and Treatments
ResumoTo the Editor: We read with great interest the article by Molho-Pessach et al1Molho-Pessach V. Agha Z. Aamar S. Glaser B. Doviner V. Hiller N. et al.The H syndrome: a genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin with systemic manifestations.J Am Acad Dermatol. 2008; 59: 79-85Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar in the July 2008 issue of the Journal entitled “The H syndrome: A genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin with systemic manifestations,” in which the authors described 11 patients with unique features including progressive sclerodermatous thickening, mainly of the skin of the middle and lower parts of the body, with overlying hyperpigmentation and hypertrichosis. Short stature, sensorineural deafness, and hepatosplenomegally were important additional features. All of the patients had markedly elevated erythrocyte sedimentation rates (ESRs). All cutaneous histopathologic examinations showed a thickened hyperpigmented epidermis, dermal and subcutaneous fibrosis, and plasma cell and mast cell infiltration. The authors suggested the title “H syndrome” to highlight the characteristic features of the skin changes—namely, hyperpigmentation and hypertrichosis. They stated that such a constellation of clinical and histopathologic findings were not reported before except in three recently published reports.2Hamadah I.R. Banka N. Autosomal recessive plasma cell paniculitis with morphea-like clinical manifestation.J Am Acad Dermatol. 2006; 54: S189-S191Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 3Marina S. Broshtilova V. POEMS in childhood.Pediatr Dermatol. 2006; 23: 145-148Crossref PubMed Scopus (28) Google Scholar, 4Prendiville J. Rogers M. Kan A. de Castro F. Wong M. Junker A. et al.Pigmented hypertrichotic dermatosis and insulin dependent diabetes: manifestations of a unique genetic disorder?.Pediatr Dermatol. 2006; 24: 101-107Crossref Scopus (40) Google Scholar We have reported six strikingly similar cases (Table I) in the International Journal of Dermatology.5El-Darouti M.A. Marzouk S.A. Abdel-Halim M.R. Muckle–Wells syndrome: report of six cases with hyperpigmented sclerodermoid skin lesions.Int J Dermatol. 2006; 45: 239-244Crossref PubMed Scopus (20) Google Scholar One of our patients had a retracted penis (Fig 1), as did four of the male patients in the article by Molho-Pessach et al.1Molho-Pessach V. Agha Z. Aamar S. Glaser B. Doviner V. Hiller N. et al.The H syndrome: a genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin with systemic manifestations.J Am Acad Dermatol. 2008; 59: 79-85Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar However, most of our patients were females, and one of them had primary amenorrhea, indicating an underlying endocrinal disorder. An important finding in our patients was that the peculiar hyperpigmented and hypertrichotic sclerodermoid skin plaques were preceded by recurrent cellulitis-like lesions.Table IClinical, laboratory, and histopathologic findings in our six reported cases5El-Darouti M.A. Marzouk S.A. Abdel-Halim M.R. Muckle–Wells syndrome: report of six cases with hyperpigmented sclerodermoid skin lesions.Int J Dermatol. 2006; 45: 239-244Crossref PubMed Scopus (20) Google ScholarPatient no.Finding123456Hyperpigmented, sclerotic, and hypertrichotic plaques++++++Deafness+++–++Hepatosplenomegally+–+–––Attacks of recurrent urticaria++––––Lesions preceded by cellulitis-like lesions––++––Renal amyloidosis–––+–+Arthralgia+–++++ESRElevatedElevatedElevatedElevatedElevatedElevatedCRPElevatedElevatedElevatedElevated——SAPElevatedElevatedElevatedElevatedElevatedElevatedIL-6—ElevatedElevatedElevated—ElevatedHistopathologic findingsMarked thickening of the dermis, sclerosis of collagen, perivascular and interstitial mixed infiltrate, and focal degeneration of elastic fibersCRP, C-reactive protein; ESR, erythrocyte sedimentation rate; IL-6, interleukin-6; SAP, serum amyloid protein. Open table in a new tab CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; IL-6, interleukin-6; SAP, serum amyloid protein. It is obvious that our article,5El-Darouti M.A. Marzouk S.A. Abdel-Halim M.R. Muckle–Wells syndrome: report of six cases with hyperpigmented sclerodermoid skin lesions.Int J Dermatol. 2006; 45: 239-244Crossref PubMed Scopus (20) Google Scholar the article by Molho-Pessach et al,1Molho-Pessach V. Agha Z. Aamar S. Glaser B. Doviner V. Hiller N. et al.The H syndrome: a genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin with systemic manifestations.J Am Acad Dermatol. 2008; 59: 79-85Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar and the authors of the other three recently reported cases2Hamadah I.R. Banka N. Autosomal recessive plasma cell paniculitis with morphea-like clinical manifestation.J Am Acad Dermatol. 2006; 54: S189-S191Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 3Marina S. Broshtilova V. POEMS in childhood.Pediatr Dermatol. 2006; 23: 145-148Crossref PubMed Scopus (28) Google Scholar, 4Prendiville J. Rogers M. Kan A. de Castro F. Wong M. Junker A. et al.Pigmented hypertrichotic dermatosis and insulin dependent diabetes: manifestations of a unique genetic disorder?.Pediatr Dermatol. 2006; 24: 101-107Crossref Scopus (40) Google Scholar are describing the same disorder because of the identical clinical and histopathologic findings, the elevated ESRs, and the sensorineural deafness. Moreover, most of the reported patients are of Arab descent.1Molho-Pessach V. Agha Z. Aamar S. Glaser B. Doviner V. Hiller N. et al.The H syndrome: a genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin with systemic manifestations.J Am Acad Dermatol. 2008; 59: 79-85Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, 2Hamadah I.R. Banka N. Autosomal recessive plasma cell paniculitis with morphea-like clinical manifestation.J Am Acad Dermatol. 2006; 54: S189-S191Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 5El-Darouti M.A. Marzouk S.A. Abdel-Halim M.R. Muckle–Wells syndrome: report of six cases with hyperpigmented sclerodermoid skin lesions.Int J Dermatol. 2006; 45: 239-244Crossref PubMed Scopus (20) Google Scholar However, we think that these unique features represent a variant of Muckle–Wells syndrome (MWS) for the following reasons:1.MWS is an inflammatory disorder characterized clinically by sensorineural deafness, recurrent inflammatory eruption, and arthritis, which in many cases could be associated with other features, such as hepatosplenomegally1Molho-Pessach V. Agha Z. Aamar S. Glaser B. Doviner V. Hiller N. et al.The H syndrome: a genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin with systemic manifestations.J Am Acad Dermatol. 2008; 59: 79-85Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, 5El-Darouti M.A. Marzouk S.A. Abdel-Halim M.R. Muckle–Wells syndrome: report of six cases with hyperpigmented sclerodermoid skin lesions.Int J Dermatol. 2006; 45: 239-244Crossref PubMed Scopus (20) Google Scholar and growth retardation.1Molho-Pessach V. Agha Z. Aamar S. Glaser B. Doviner V. Hiller N. et al.The H syndrome: a genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin with systemic manifestations.J Am Acad Dermatol. 2008; 59: 79-85Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, 3Marina S. Broshtilova V. POEMS in childhood.Pediatr Dermatol. 2006; 23: 145-148Crossref PubMed Scopus (28) Google Scholar, 5El-Darouti M.A. Marzouk S.A. Abdel-Halim M.R. Muckle–Wells syndrome: report of six cases with hyperpigmented sclerodermoid skin lesions.Int J Dermatol. 2006; 45: 239-244Crossref PubMed Scopus (20) Google Scholar All of our cases and most of the cases discussed by Molho-Pessach et al1Molho-Pessach V. Agha Z. Aamar S. Glaser B. Doviner V. Hiller N. et al.The H syndrome: a genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin with systemic manifestations.J Am Acad Dermatol. 2008; 59: 79-85Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar fulfill these clinical criteria.2.All MWS patients present with a very high ESR, as in our patients and in the other reported patients.1Molho-Pessach V. Agha Z. Aamar S. Glaser B. Doviner V. Hiller N. et al.The H syndrome: a genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin with systemic manifestations.J Am Acad Dermatol. 2008; 59: 79-85Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, 2Hamadah I.R. Banka N. Autosomal recessive plasma cell paniculitis with morphea-like clinical manifestation.J Am Acad Dermatol. 2006; 54: S189-S191Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 3Marina S. Broshtilova V. POEMS in childhood.Pediatr Dermatol. 2006; 23: 145-148Crossref PubMed Scopus (28) Google Scholar, 4Prendiville J. Rogers M. Kan A. de Castro F. Wong M. Junker A. et al.Pigmented hypertrichotic dermatosis and insulin dependent diabetes: manifestations of a unique genetic disorder?.Pediatr Dermatol. 2006; 24: 101-107Crossref Scopus (40) Google Scholar3.Important laboratory diagnostic findings of MWS, including elevated interleukin 6 (IL-6) and serum amyloid protein levels, were found in most of our published cases (Table I) and in three additional unpublished cases that we diagnosed after the publication of our first report.4.The elevation of IL-6 in MWS can account for the deafness, because IL-6 can act as an osteoclast-activating factor, which may eventually cause destruction of the costi organ, leading to sensorineural deafness and by a similar mechanism cause the persistent arthritis.6Jilka R.L. Hangoc G. Girasole G. Passeri G. Williams D.C. Abrams J.S. et al.Increased osteoclast development after estrogen loss: mediation by interleukin-6.Science. 1992; 257: 88-91Crossref PubMed Scopus (1303) Google Scholar5.The elevated SAP in all of our patients was associated with renal amyloidosis in two of them. Renal amyloidosis was reported to occur in about 30% of MWS patients. The possible deficiency of inflammatory cascade inhibitors or the cytokine receptor abnormalities7Berthelot J.M. Maugars Y. Robillard N. Pascal O. Stalder J.F. David A. et al.Autosomal dominant Muckle–Wells syndrome associated with cystinuria, ichthyosis, and aphthosis in a four-generation family.Am J Med Genet. 1994; 53: 72-74Crossref PubMed Scopus (16) Google Scholar may explain both the marked elevation of IL-6 and proinflammatory mediators and can cause recurrent inflammation of the skin that may eventually lead to increased growth factors production and subsequent thickening of the epidermis, dermis, and subcutaneous tissue. The constant finding of perivascular and interstitial mixed inflammatory infiltrate of plasma cells, histiocytes, eosinophils, and mast cells (Fig 2) is an important indicator of the inflammatory nature (probably mediated by IL-6) of the skin lesions. In our patients, we have attempted treatment of the skin lesions and arthritis with colchicine and ultraviolet A light phototherapy (3 times/week), with two cases showing 50% improvement of the indurations after 8 weeks. We would be delighted to cooperate with Molho-Pessach et al1Molho-Pessach V. Agha Z. Aamar S. Glaser B. Doviner V. Hiller N. et al.The H syndrome: a genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin with systemic manifestations.J Am Acad Dermatol. 2008; 59: 79-85Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar to verify the relation of this unique disorder to MWS. ∗Please see the August issue (Molho-Pessach V, Zlotogorski A. H syndrome and Muckle–Wells syndrome. J Am Acad Dermatol 61:365) for a response to this letter. The H syndrome: A genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin with systemic manifestationsJournal of the American Academy of DermatologyVol. 59Issue 1PreviewThe association of cutaneous hyperpigmented, hypertrichotic, and indurated patches associated with hearing loss, short stature, cardiac anomalies, hepatosplenomegaly, scrotal masses, and hypogonadism has not, to our knowledge, been previously recognized as a disease entity. Full-Text PDF H syndrome and Muckle–Wells syndromeJournal of the American Academy of DermatologyVol. 61Issue 2PreviewTo the Editor: We thank Dr El-Darouti for his interest in our paper.1 We completely agree that the patients described by El-Darouti et al2 are clinically and histologically similar to our patients. We believe that his patients indeed suffer from H syndrome and not from a variant of Muckle–Wells syndrome with “peculiar hyperpigmented and hypertrichotic sclerodermoid skin plaques.” This type of cutaneous involvement is typical for H syndrome. Furthermore, Muckle–Wells is an autosomal dominant syndrome, and the responsible gene is CIAS1,3 while H syndrome is an autosomal recessive syndrome caused by mutations in the SLC29A3 gene. Full-Text PDF
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