Table of Contents
Introduction:
Stiff skin syndrome is a rare dermatological condition affecting the entire body. It is a non-inflammatory and progressive disease with onset in infancy or childhood. Generally, it is a group of genetic muscle diseases that can occur at birth or during early infancy. The condition affects the skin and muscles and is characterized by stony, hard, tight skin with skin thickening. It allows the person difficulty in moving their joints freely. The main cause of the occurrence of stiff skin syndrome is genetic mutations. Genetic testing and physical examination help in diagnosing the condition. However, there is no cure for the condition, but the treatment, such as medications and physical therapy, focuses on managing symptoms. The article discusses stiff skin syndrome, its causes, symptoms, diagnosis, treatment, and prevention.
What Is Stiff Skin Syndrome?
Stiff skin syndrome is a rare autoimmune and slowly progressive disease that causes muscle stiffness and muscle spasms. The symptoms may come and go and worsen with time. Stiff skin syndrome was first described in 1971 and named after the appearance of symptoms, which were described as episodes of muscles becoming stiff as hard as some. It is also called congenital fascial dystrophy. Although the condition affects the entire body, the shoulders, lower back, thighs, and buttocks are mainly affected. The condition is similar to scleroderma or systemic sclerosis.
What Are the Causes of Stiff Skin Syndrome?
It is a genetic condition that affects children from birth and people in adulthood. Stiff skin syndrome is caused by genetic mutations in the gene FBN1 (fibrillin-1). The gene is responsible for making or producing a protein called fibrillin-1. Fibrillin-1 protein is essential for the strength and elasticity of connective tissue within the body, such as skin, muscles, and other body structures. FBN1 protein is the major component of the extracellular matrix microfibrils. These microfibrils provide structural support for elastin deposition.
When there is a mutation in the gene FBN1, the function and production of the fibrillin-1 protein get disrupted. Several variants affecting the FBN1 protein cause impaired latent transforming growth factor (TGF)-beta signaling, elevated TGF-beta concentration in the skin, and excessive microfibrillar deposition. This affects the connective tissue and leads to symptoms, such as limitation of joint motion. Mutations in the FBN1 gene are typically inherited in an autosomal dominant manner. This means the person needs only one copy of an inherited gene from a single parent to develop the condition. In some cases, it occurs without any family history of the condition.
What Are the Signs and Symptoms of Stiff Skin Syndrome?
There are two clinical subtypes of stiff skin syndrome: widespread stiff skin syndrome and segmental stiff skin syndrome. The distribution of the skin lesions, the time of onset, and the severity of musculoskeletal involvement distinguish these two types.
Widespread Stiff Skin Syndrome: This is the most common type of stiff skin syndrome. It affects people during infancy or early childhood. Congenital fascial dystrophy is a subset of stiff skin syndrome with predominant fascial involvement and less severe skin tightening.
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Dermatological Features: The condition is progressive, affecting bilateral skin overlying areas with abundant fascia, such as thighs and buttocks. It makes the stony hard skin, thick skin, and stiff skin that is firmly bound to the underlying tissues. The affected skin feels like wood, stone, or board. It can be difficult to pinch or move over the affected area. The skin can be visible normally or with mild hyperpigmentation. In one-third of cases, mild hypertrichosis (hair growth over the affected area) is noted over the affected areas. Some people may experience muscle weakness. There can be differences in the color and texture of the skin with a lack of sweating. In some cases, the facial skin may become tight, leading to limited mobility of facial expression.
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Extracutaneous Features: Tight skin can limit the range of motion in the joints, mainly in the shoulders, elbows, hips, and knees. The situation may require help performing daily activities. The person makes it harder to perform activities that require bending or stretching. If the condition is left untreated, the symptoms may worsen, causing contracture of the large joints over months to years. This may result in lipodystrophy (loss of body fat), a narrow thorax, scoliosis (curve in the spine), and tiptoe gait (a person walking on their toe). In severe cases, there will be chest wall deformities and growth retardation resulting in short stature.
Segmental Stiff Skin Syndrome: It is a less common form of stiff skin syndrome that may affect a person in childhood or early adulthood. The cutaneous and extracutaneous clinical features are the same as widespread stiff skin syndrome, but the symptoms are less severe. The lesions are unilateral, and the result is joint contractures and mobility limitations.
How Is Stiff Skin Syndrome Diagnosed?
The condition can be diagnosed with patient history, physical examination, and skin biopsy. The detailed description of the diagnosis of stiff skin syndrome is as follows:
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Patient History: The healthcare provider may ask the patient about the onset of the symptoms, associated pain, onset of the condition in infancy or childhood, bilateral skin induration, and involvement of the affected areas, such as shoulders or pelvic girdles. In addition, the doctor may ask the patient about the family history of the condition.
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Physical Examination: The healthcare provider may physically examine the patient to assess the location and extent of indurated areas bound to the underlying tissues and the presence of skin inflammation with sclerosis.
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Skin Biopsy: The healthcare provider may perform a skin biopsy, in which they take a sample of deep skin, including the dermis, epidermis, and subcutis (the deepest layer of the skin), and send it to the laboratory for histopathological examination with routine stains or fibroblast markers.
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Laboratory Tests: The doctor may also check the complete blood count, sedimentation rate, electrolytes, C-reactive proteins, rheumatoid factor, and thyroid-stimulating hormone to rule out inflammatory and immune-mediated diseases.
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Imaging Studies: The doctor may perform magnetic resonance imaging (MRI) and X-ray to assess joint contractures, bone involvement, and skeletal deformities.
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Genetic Testing: DNA (deoxyribonucleic acid) sequencing is performed to find the variants in the FBN1 gene. This can confirm the diagnosis.
How Is Stiff Skin Syndrome Treated?
There is no cure for stiff skin syndrome. Management strategies include physical therapy, psychological support, and social support.
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Physical Therapy: Careful physiotherapy or massage can be given to the patient to improve muscle strength and joint movement. The use of corrective splints may also be helpful.
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Pharmacological Therapy: The healthcare provider may prescribe medications, such as glucocorticoids, drugs with anti-fibrotic growth factors, and immunosuppressants. Losartan is an angiotensin receptor antagonist that can be prescribed to children and adults. Immunosuppressive agents, such as Mycophenolate mofetil, are prescribed with physical therapy to improve joint mobility.
What Is the Differential Diagnosis of Stiff Skin Syndrome?
The differential diagnosis of stiff skin syndrome is as follows:
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Systemic sclerosis.
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Scleroderma (autoimmune disease causing skin thickening).
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Eosinophilic fasciitis (tissue under the skin and over the muscles are swollen and inflamed).
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Mucopolysaccharidoses (a genetic condition that causes sugar excretion in urine).
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Sclerema neonatorum (a condition affecting the subcutaneous fat of newborn babies).
Conclusion:
Stiff skin syndrome is a rare progressive disease affecting the skin and muscles. The affected person may have difficulty performing daily activities due to limited joint mobility. Physical examination and imaging studies aid in diagnosing the condition. Physical and pharmacological therapy helps manage stiff skin syndrome. However, further advancement is needed to manage the condition.
