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Stiff skin syndrome: Hard in many ways

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By Warren R. Heymann, MD
July 4, 2016

Stiff skin syndrome (SSS) is a noninflammatory, fibrosing condition of the skin and fascia, often affecting the limb girdle region, notably the buttock and thighs, resulting in a lordotic posture. It may be accompanied by subtle hypertrichosis and hyperpigmentation. The course tends to be chronic and progressive. The visceral or immunologic features of systemic sclerosis do not accompany it, and the clinical and histologic features differentiate SSS from other sclerodermoid conditions (sclerema neonatorum, scleredema, scleromyxedema, and sclerodermatomyositis) (1).

Familial and consanguineous reports account for 30% of cases of SSS. There is evidence that a heterozygous mutation of the fibrillin-1 gene (FBN1), regulating the profibrotic cytokine transforming growth factor b2 may be pathogenic (2). Although mutations in FBN1 have been noted in Marfan syndrome, Jensen et al have demonstrated that “substitutions in fibrillin-1 domains TB4 and TB5 that cause SSS and the acromelic dysplasias do not prevent fibrillin-1 from being secreted or assembled into microfibrils, whereas MFS-associated substitutions in these domains result in a loss of recombinant protein in the culture medium and no association with microfibrils. These results suggest fundamental differences in the dominant pathogenic mechanisms underlying MFS, SSS and the acromelic dysplasias, which give rise to TGFβ dysregulation associated with these diseases” (3).

Myers et al detail 4 patients with SSS with a predominantly unilateral, segmental distribution. In their review of the literature, they found of the 52 cases (48 in the literature in addition to their 4 patients), 18 (35%) were segmentally distributed and 35 (65%) were widespread. The segmental cases had a later age of onset (4.1 years) compared to patients with diffuse disease (1.6 years). Joint mobility was limited in less than half (44%) of the patients with segmental disease compared to virtually all (97%) of those with widespread involvement. Histologically, both types were identical, with thickened collagen bundles around mature adiopocytes, and increased mucin deposition. The authors propose that the limited form of SSS may be due to mosaic mutation of the FBN1 gene (4).

Other than physical therapy, to date there is no satisfactory treatment of SSS. Methotrexate, peniclliamine, topical steroids, PUVA, and calcipotriene have not been valuable (5).

I have only seen one patient with SSS presented at a conference. I know how hard this is literally but can only imagine how hard it is figuratively — on the patient, their families, and physicians. The importance of this article is recognizing that there is a subset of patients where the prospects may not be as dire. Perhaps novel techniques at modulating the FBN1 gene or targeted therapy directed to TGFβ can be developed.

1. Amormin AG, et al. Stiff skin syndrome-case report. An Bras Dermatol 2011; 86 (4 Suppl 1) S178-81.
2. OMIM 184900
3. Jensen SA, et al. A microfibril assembly assay identifies different mechanisms of dominance underlying Marfan syndrome, stiff skin syndrome and acromelic dysplasias. Hum Mol Genet 2015; 24: 4454-63.
4.Myers KL, et al. Segmental stiff skin syndrome (SSS): A distinct clinical entity. J Am Acad Dermatol 2016; 75; 163-8.
5. Ogunmakin K, et al. A 7-year old with indurated skin and unilateral progressive joint mobility: A case of stiff skin syndrome. Dermatol Online J 2015 Sept 17: 21(9)

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