Stiff skin syndrome is a rare genetic connective tissue disorder that manifests at birth or in early childhood. ¹ Patients suffer from rock-hard or rock-hard skin all over their body, with enormous fascia in places like the thighs and buttocks. It causes reduced joint mobility in the affected area and in some cases hypertrichosis. ² In our clinic we present the case of a girl with stiff skin syndrome associated with bone involvement at the femoral head, using the CAse REport (CARE) guidelines as a guiding principle. ³

Esterly and McKusic ¹ were the first to describe stiff skin syndrome, also known as congenital fascial dystrophy and mucopolysaccharidosis. It is a rare, genetically inherited connective tissue disease similar to scleroderma. Manifestations of the syndrome typically begin at birth, in infancy or early childhood. ² It is caused by mutations in the ArgGlyAsp (RGD) sequence-encoding domain of the fibrillin-1 (FBN1) encoding gene. As a result of altered transforming growth factor (TGF) ^{4 – 6} activation and signaling, this promotes profibrotic activation. As a result, the elastic fibers responsible for skin rebound are replaced with fibrotic deposits. Despite cutaneous involvement, the visceral and adjacent muscles are usually unaffected and there are no immunological or vascular changes. ⁷

The exact cause of stiff skin syndrome is unknown. Postulations include abnormal mucopolysaccharide metabolism occurring exclusively in the skin and later thought to be localized in the fascia, ^{8 – 11} primary fascial dystrophy with consequent collagen overabsorption ⁷ and an inflammatory process. ^{11 , 12} The two hypotheses that have gained wider acceptance are increased collagen VI production secondary to a primary fascial abnormality and a congenital fibroblastic abnormality leading to non-inflammatory dermal fibrosis due to defective mucopolysaccharide synthesis. In addition, some investigators have found high levels of pro-inflammatory markers such as interleukin-6, transforming growth factor-2 and tumor necrosis factor-alpha, suggesting an inflammatory pathogenesis. ^{7 , 11 , 13 , 14}

Symptoms of stiff skin syndrome include a rock-hard deep skin hardening that is inherently connected to the underlying tissue, reduced joint mobility, and hypertrichosis. The buttocks, thigh and shoulder are the most affected body regions, but ocular involvement has been reported in rare cases. ¹² Diagnosis is clinical and confirmed by histological findings; therefore, a high index of suspicion is required, and the diagnosis is made by exclusion. The disease is divided into two types depending on the manifestation: widespread and segmental. The widespread stiff skin syndrome has an earlier onset, a more severe form, is more common than segmental stiff skin syndrome, and affects the joint with a more restricted range of motion and prominent bilateral involvement. Segmental stiff-skin syndrome is segmentally distributed with unilateral body affectation, has female predominance in contrast to the widespread stiff-skin syndrome, which has no gender predominance and less clinical consequences. ^{13 , 14}

The clinical findings in our patient were consistent with segmental stiff skin syndrome. This is evidenced by the unilateral involvement of the lower extremities, gluteal and trunk muscles, and limited mobility of the left hip joint. Hypertrichosis and a limping gait occurred as follow-up investigations, both of which were clinical findings. Histological findings of orthokeratotic epidermis, pandemic fibrosis, and increased collagen bundles within the deep reticular dermis confirmed the diagnosis. However, our patient has incidental bony involvement, which is rare.

Due to overlapping histopathological features with stiff skin syndrome but with classic features not seen in this patient, the two differential diagnoses of generalized morphea and systemic sclerosis were close. Scleroderma typically affects the head, face, neck, and back, with the shoulder and belt being the exceptions, but when affected, the usual sites are not exempt. Joint restriction is uncommon in scleroderma, and when skin stiffness occurs, it is due to the mass effect and typically affects an entire anatomical unit. Generalized morphea also occurs suddenly, in contrast to stiff skin syndrome, which can begin at birth. ^{15 , 16} Systemic sclerosis, on the other hand, is a pansystemic chronic autoimmune rheumatic disease characterized by degenerative changes and scarring of the skin and internal organs such as the lungs, heart, and gastrointestinal tract, as well as blood vessel abnormalities. ¹⁷

This patient was managed by a multidisciplinary team including orthopedists, physiotherapists and a dermatologist. She began receiving regular massages with emulsifying ointments, two to three sessions of physiotherapy per week, the best therapeutic option, and orthopedic check-ups every six months. Though, corticosteroids and immunosuppressive drugs have been used previously, they have not been proven effective. ^{18 , 19}

Finally, stiff skin syndrome is a non-inflammatory, fibrosing condition characterized by rock-hard, hardened skin, mild hypertrichosis, and limited joint mobility. To date, there have been no reports of skeletal abnormalities in the literature, and our case showed bone involvement affecting the femoral head.

Written informed consent for publication of their clinical details and clinical images was obtained from the parent of the patient.