Scleredema

Etiology

The scleredema of Buschke was classified into three types by Graff in 1968.

• Scleredema type 1 is the largest group and affects about 55% of the cases. It presents mostly in the pediatric population and young adults. Typically, the onset of scleredema is abrupt and starts after 2 to 3 weeks following a febrile infectious episode, usually streptococcal throat infection and less commonly a viral illness.[3]
• Scleredema type 2 encompasses about 25% of all cases. It demonstrates an insidious onset and progresses slowly, and correlates to hematological abnormalities. Paraproteinaemia is the most associated condition and always develops many years after the onset of scleredema. It occurs at a younger age when compared to the general population. Other abnormalities include monoclonal gammopathy of undetermined significance involving IgG and IgA, multiple myeloma and amyloidosis. The link between scleredema and paraprotein remains unclear.[2]
• Scleredema type 3 is referred to as scleredema diabeticorum since it involves diabetic patients.  It constitutes around 20% of cases. It is a known complication of long-lasting and poorly-controlled insulin-dependent diabetes mellitus. Severe diabetic vascular complications are usually associated. It affects 2.5% to 14% of all diabetic patients. There is a hypothesis that high glucose levels induce nonenzymatic glycosylation of collagen in the dermis.[4]

Other diseases have descriptions associated with the presentation scleredema of Buschke. They include primary hyperparathyroidism, rheumatoid arthritis, ankylosing spondylitis, Sjogren syndrome, dermatomyositis, Waldenstrom macroglobulinemia, anaphylactoid purpura, primary biliary cirrhosis, and IgA deficiency.[2] Cases of concomitant lichen sclerosus and atrophicus and scleredema adultorum of Buschke had been reported, endorsing the theory that scleroderma-like disorders share common underlying pathogenesis.[5] Rare cases of scleredema of Buschke have carry associations with concomitant neoplasms.[6]

Epidemiology

The exact incidence of scleredema of Buschke is unknown. The disease can occur at any age. There is no racial predilection. The first group mostly involves children and young adults — the second and third types of scleredema concern elderly patients (over forty years old). Male predominance is noted in type 1 and type 2 sclerema (sex-ratio around 2). In contrast, the male to female ratio approaches 10 to 1 in type 3.

Pathophysiology

Scleredema of Buschke is a skin connective tissue disease of unknown pathogenesis. Increased production of collagen type 1 and glycosaminoglycans by fibroblasts of the reticular dermis presented, as well as deposition of mucopolysaccharides in the interfibrillar spaces in the dermis. This phenomenon may become triggered by diverse stimuli, including infections, drugs, immunoglobulins, genetic factors, hyperinsulinism, and inflammatory processes.[7]

Histopathology

The skin biopsy is not required to confirm the diagnosis, but it is useful to exclude other scleroderma-like disorders. Histologic examination of the mid and the reticular dermis shows marked thickening of the collagen bundles, separated from one another by prominent, clear mucin-filled spaces. A mild mononuclear inflammatory infiltrates surrounding capillaries are observable. The subcutaneous fat shows invasions with enlarged collagen fibers. No abnormalities of the epidermis, the sweat glands or the pilosebaceous glands are present. Mucin deposits are observed in most cases, using Alcian blue or toluidine blue stains.[8]

History and Physical

The scleredema of Buschke Type 1 has an abrupt onset. The occurrence of febrile illness in the past 2 to 3 weeks should guide the diagnosis. In contrast, type 2 and 3 have a progressive course and diagnosis delays in most cases for several years. Transient erythema or annular rash may precede skin induration. The scleredema may cause pruritus and less commonly, pain. Patients usually complain about the limited motion of the shoulders and the temporomandibular joint with difficulty of mastication.

Physical examination shows a poorly-defined woody and non-pitting induration of the skin, with inconstant overlying erythema or hyperpigmentation. It first involves the neck and then spreads to the shoulders, the upper trunk, and the arms symmetrically. It can reach the face, and rarely the buttocks and thighs. Interestingly, the swelling spares the hands and feet. The affected skin has a ‘peau d’orange’ appearance when pinched.[2] There are reports of diffuse forms involving the whole dermis.[3] Unusual presentations include asymptomatic bilateral eyelid edema of sudden onset, presenting as periorbital edematous swelling.[1][9]

Extra-cutaneous involvement is exceptional, especially in types 2 and 3 scleredema. It affects mostly the tongue and the heart, but also the lungs, skeletal muscles, esophagus, parotid glands, liver, spleen, pleurae, and eyes. Complications include restricted motility, dysphagia, sicca syndrome, pleural or pericardial or peritoneal effusions. Symptoms of malignancies or complicated diabetes require careful vigilance.[2]

Evaluation

The diagnosis of scleredema has its basis in clinical and histological characteristics. No laboratory tests or immunological examinations are needed. It is recommended to perform a screening for paraproteins to identify a lymphoproliferative disorder.[10] The skin thickness may be measured using ultrasonography. It helps to evaluate the activity and severity of the disease.[11]

Treatment / Management

There is no specific therapy for scleredema of Buschke. Various therapeutic alternatives are proposed to alleviate the symptoms. Phototherapy represents first-line treatment. In unresponsive or severe cases, intravenous immunoglobulin is a recommended option.[12][13][14](B3)

Treatment of the underlying cause is required. In scleredema type 1, antibiotics are indicated in the case of streptococcic infection. Patients of type 2 require management by a hematologist. Tight control of diabetes in urged for patients of type 3, although there is no clear improvement of scleredema. Other therapies include steroids, cyclosporine, penicillamine, cyclophosphamide, electron beam therapy, high doses of intravenous penicillin.[2] However, no approach had shown consistent results, and most patients describe partial remission. Physical therapy is a recommendation for patients with limited mobility caused by scleredema.

Differential Diagnosis

All diseases sharing with edema and mucin deposition must merit consideration among the differential diagnosis of scleredema of Buschke. It is commonly confused with scleromyxedema and scleroderma disorders.

Scleroderma is usually observed in systemic sclerosis and typically presents as asymmetrical thickening of the skin with pigmentation and centripetal progression. Typically, there system involvement and presence of scleroderma-specific autoantibodies, Raynaud phenomenon, and nail fold capillary abnormalities. Histopathology shows excessive collagen resulting in the thickened dermis. The distinction between scleredema and scleroderma usually has a basis on clinical features, rather than histological findings.

Scleromyxedema is also a scleroderma-like disorder. They both share the mucin dermal deposition and development of paraproteinemia. Scleromyxedema presents as cutaneous lichenoid papules that extend and form hardened plaques involving the face, the neck, and the arms and can be generalized. Unlike scleredema, it affects the hands and the fingers. Histologically it is characterized by dermal fibrosis with dermal fibers separated by excessive mucin deposits composed mainly of hyaluronic acid. Systemic involvement is common, secondary to mucin deposits. It may also be associated with monoclonal gammopathy, multiple myeloma, and thyroid dysregulation.[8]

Prognosis

The prognosis of the scleredema of Buschke highly depends on the subtype. In type 1 patients, the scleredema is self-limiting and usually resolves spontaneously within 6 to 24 months. Reports exist of longer course up to ten years. In type 2 and 3, the disease progresses slowly with possible systemic involvement and life-threatening complications.