Dermatology

Stiff Skin Syndrome (Mucopolysaccharidosis)

Stiff Skin Syndrome

Are You Confident of the Diagnosis?

Stiff skin syndrome is a peculiar condition with sclerodermoid changes, which was described in 1971 by Esterly and McKusic. Skin changes have an early onset in infancy, even from the time of birth, and are characterized by stony-hard skin induration, which is strongly bound, adherent to the deeper underlying tissues. Cases could be localized or may have large areas affected, they may be sporadic, but around 40% are familial.

A condition described as familial progressive scleroderma could be a clinical variant. Another possible variant was described and named congenital fascial dystrophy. In this case, fascial thickening is observed with important limb contraction and mobility limitation. Hypertrichosis may be associated in the half of cases and helps to establish the diagnosis.

The most common localizations are the thighs and buttocks, although cases in the shoulders were also reported (Figure 1, Figure 2). The condition could be considered as an localized mucopolysaccharidosis without urinary excretion of mucopolysaccharides. The only extracutaneous manifestation is joint mobility restriction, which is secondary to the skin changes. It could be strong enough to impair normal ambulation. Ventilatory limitation was described in cases with thoracic involvement.

Figure 1.

Normochromic sclerotic changes in the tigh with light hypertrichosis.

Figure 2.

Sclerotic plaque on the back.

There is no visceral involvement nor any serologic abnormalities. Patients do not show dysmorphic traits and have a normal face. Acrosclerosis is not found, which may help to exclude scleroderma, a difficult differential diagnosis.

Who is at Risk for Developing this Disease?

Risk factors are not known. Genetic predisposition is possible in affected families. In some families an autosomal dominant inheritance was reported.

What is the Cause of the Disease?

Etiology

Mutations in the FBN1 gene, which encodes fibrillin-1, a protein involved in elastic fiber assembly, were reported. These mutations could lead to altered cell-matrix interactions and to fibrotic changes.

Pathophysiology

Light microscopy shows dermal thickening with abundant collagen with increased cellularity (Figure 3, Figure 4). Important inflammation or vessel changes are not seen. Deposition of mucopolysaccharides could be demonstrated with proper staining. Transmission electron microscopy of congenital fascial dystrophy revealed giant fibrils in the affected fascia. Myofibroblasts were demonstrated in the lesions. Complications are due to skin induration, such as limited mobility, ambulation restriction, and respiratory impairment.

Figure 3.

Dense dermal collagen with increased cellularity.

Figure 4.

Increased collagen with preserved dermal adnexes.

Systemic Implications and Complications

Complications are due to skin induration, such as limited mobility and ambulation restriction and respiratory impairment.

Treatment Options

Physiotherapeutic exercises to improve skin induration and joint mobility limitation. Systemic steroids were used but there is no consensus about their efficacy.

Optimal Therapeutic Approach for this Disease

Physiotherapy to improve joint restriction.

Patient Management

The condition has a good prognosis, since there is no visceral involvement. Working with physical therapy is essential for this disrorder.

Unusual Clinical Scenarios to Consider in Patient Management

Respiratory complications such as pneumonia and respiratory insufficiency in cases with thoracic involvement.

What is the Evidence?

Esterly, NB, McKusic, VA. "Stiff skin syndrome". Pediatrics. vol. 47. 1971. pp. 360-9.

(First four patients were reported with localized areas of stony-hard skin, hirsutism, and limitation of joint mobility. Three cases were congenital and one was first noticed in early childhood. Light microscopy showed abnormal deposition of hyaluronidase-digestible acid mucopolysaccharide in the dermis. Increased urinary excretion of mucopolysaccharide was not found. Autosomal dominant inheritance was suggested.)

Jablonska, S, Blaszczyk, M. "Stiff skin syndrome is highly heterogeneous, and congenital fascial dystrophy is its distinct subset". Pediatr Dermatol. vol. 21. 2004. pp. 508-10.

(The authors describe a condition with deeper fibrosis and suggest the term “congenital fascial dystrophy” for this variant.)

Mat, C, Kalayciyan, A, Arzuhal, N. "Stiff skin syndrome: a case report". Pediatr Dermatol. vol. 20. 2003. pp. 339-41.

(The authors report the first Turkish case, a 15-year-old girl with skin hardening and joint movement limitation.)

Liu, T, McCalmont, TH, Frieden, IJ. "The stiff skin syndrome: case series, differential diagnosis of the stiff skin phenotype, and review of the literature". Arch Dermatol. vol. 144. 2008. pp. 1351-9.

(The authors describe six children with stony-hard skin changes on the thighs, buttocks, and lower back, two cases showed shoulder and arm involvement that fit criteria for stiff skin syndrome. Hypertrichosis was seen in half of them. Joint restriction with postural impairment was found. Light microscopy showed fascial sclerosis or showed increased fibroblast cellularity without associated inflammation.)

Geng, S, Lei, X, Toyohara, JP. "Stiff skin syndrome". J Eur Acad Dermatol Venereol. vol. 20. 2006. pp. 729-32.

(A case from Chine with skin induration, mild hypertrichosis and limited joint mobility with localization on the buttocks and thighs was described.)

Caspary, P, Costa, F, Souza, PRM, Duquia, RP, Almeida, HL. "Familial localized stiff skin syndrome". Int J Dermatol. vol. 49. 2010. pp. 843-5.

(A Brazilian family with localized shoulder involvement is reported. Light microscopy showed deposition of dermal mucopolysaccharids with increased cellularity. Autosomal dominant inheritance was suuggested.)

Loeys, BL, Gerber, EE, Riegert-Johnson, D. "Mutations in fibrillin-1 cause congenital scleroderma: stiff skin syndrome". Sci Transl Med. vol. 23. 2010. pp. 23ra20.

(Mutations in the gene of fibrillin-1 were described. These mutations could lead to altered cell-matrix interactions and to fibrotic changes.)
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