Background
Scleredema is an uncommon, but likely underrecognized, fibromucinous connective-tissue disease. It is characterized clinically by woody induration and hardening of the skin that results from excessive mucin deposition between thickened collagen bundles in the skin's dermis. The term scleredema is a misnomer because neither sclerosis nor edema is found on microscopic examination.
There are three clinical forms of scleredema, which are classified by their associated condition. Scleredema may be associated with a history of an antecedent infection (type 1), a blood dyscrasia (type 2), or diabetes mellitus (type 3). Each of these clinical forms has a different history, course, and prognosis. There are also rare reports of scleredema associated with other disorders, as well as occurring independent of an associated disorder. Additional reported associations include the following:
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Hyperparathyroidism [1]
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Rheumatoid arthritis and Sjögren syndrome [2]
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HIV disease and AIDS–related lipodystrophy syndrome [3]
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Malignant insulinoma [4]
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Carcinoid of the gall bladder [5]
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Carcinoid tumor [6]
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Lichen sclerosus [7]
Scleredema can be a self-resolving or a persistent skin condition. It is typically considered benign, but it can involve internal organs and rarely may result in death. There is no standard therapeutic protocol, as therapeutic success in the literature is limited to case reports.
Pathophysiology
Increased deposition of collagen and mucin (hyaluronic acid, an acid mucopolysaccharide) is seen in this condition; however, the causative mechanism is unknown.
Theories for diabetes-associated scleredema include accumulation of collagen as the result of irreversible collagen glycosylation and resistance to degradation by collagenase; alternatively, increased collagen synthesis due to excess insulin stimulation, microvascular damage, and hypoxia has been suggested.
Theories for nondiabetic scleredema include molecular mimicry, in which streptococcal antigens cross-react with components of the dermis resulting in an antigen-antibody reaction.
Etiology
The cause of scleredema is unknown; however, it is associated with a number of conditions. Many patients have no history of an acute antecedent illness. Note the following:
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Febrile illness with streptococcal infections [8, 9] : An upper respiratory tract infection (typically pharyngitis) is the most common cause of scleredema in patients with type 1 scleredema. Scleredema following scabies infestation, as a result of superinfection with Streptococcus, has been reported. [10]
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Other infections: The onset of scleredema has also been associated with cytomegalovirus infection, influenza, measles, pertussis, mumps, diphtheria, typhus fever, encephalitis, and dental abscesses.
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Myelomatous disorders [11, 12] : A subset of patients with type 2 scleredema has shown a well-established relationship between scleredema with paraproteins and multiple myeloma. One analysis of 52 patients with group 2 scleredema revealed 25% had plasma cell dyscrasia, including 3 patients with multiple myeloma and 10 with monoclonal gammopathy of unknown significance. [13]
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Trauma: Rare reports exist of scleredema occurring after trauma to the affected area. One report has described geometric scleredema due to mechanical stress. [16]
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Drug reaction: In 2005, scleredema was reported in association with the use of infliximab; although rare, treating physicians should consider the possibility of an adverse drug reaction as the underlying etiology. [17]
Epidemiology
Frequency
Worldwide, scleredema is rare, although diabetes-related scleredema is likely underreported. [18, 19]
Race
No racial predilection is reported for scleredema.
Sex
A female preponderance is reported for scleredema, with a female-to-male ratio of 2:1 for non–diabetes-related scleredema. Adult-onset diabetes associated scleredema is much more common in men, with a male-to-female ratio of 10:1.
Age
Scleredema occurs in individuals of all ages, ranging from infancy to adulthood. [20] Although scleredema is sometimes referred to as scleredema adultorum, 50% of scleredema cases occur in individuals younger than 20 years. The majority of childhood cases are postinfectious and self-resolving. [21, 22]
Prognosis
The course of scleredema is unpredictable. Patients with type 1 scleredema, particularly pediatric patients, typically have a self-limited course, with the disease resolving in 6 months to 2 years. However, a number of reports exist in which these patients had a protracted course or, rarely, long-term cardiac or skeletal muscle involvement. Patients with types 2 and 3 typically have a slowly progressive or unremitting course over many years. Reports of relapses following apparent improvement also exist.
Typically, scleredema is a benign process limited to the skin. The skin changes of scleredema can cause limitations of movement. Rarely, this can include reductions in joint mobility, difficulty opening eyes or mouth, or restrictive lung disease in extensive trunk involvement.
Although the disorder is usually restricted to the skin, the tongue, pharynx, esophagus, skeletal muscle, and cardiac muscle may rarely be affected. Rare case reports of morbidity due to extracutaneous collagen and mucin deposition include the following:
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Tongue involvement: Unlike scleroderma, the tongue has been reported in scleredema, resulting in dysarthria and difficulty with mastication and tongue protrusion.
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Other organs involvement: Skeletal muscles, ocular muscles, the pharynx, the liver, parotid glands, pleurae, the peritoneum, and the spleen reportedly may be involved.
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Esophageal involvement: In one report, a patient with scleredema developed dysphagia, presumably from scleredema of the upper part of the esophagus. Esophageal biopsy was not performed on this patient. [23]
Death from scleredema is rare. However, reports have described patients dying from the complications of cardiac or respiratory involvement. [13, 24]
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Middle-aged man who has diabetes with scleredema on the upper part of the back.
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Middle-aged man who has diabetes with scleredema on the upper part of the back.
