Scleredema

Background

This dermal mucinosis is also known as scleredema adultorum of Buschke. It presents as indurated skin usually in women, occurring on the posterior neck, shoulders, upper trunk, and face. There are several clinical variants and associations. There also may be an associated paraprotein and involvement of the skeleton, eyes, and tounges.

Clinical Presentation Description

Acute Occurs after a few days or weeks following a febrile illness caused by streptococcus or a virus

Insidious No preceeding illness
Protracted course

Insidious and prolonged Associated with insulin dependent diabetes mellitus

OUTLINE

Epidemiology

Disease Associations

Pathogenesis

Laboratory/Radiologic/Other Diagnostic Testing

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Special Stains/
Immunohistochemistry/
Electron Microscopy

Differential Diagnosis

Prognosis and Treatment

Commonly Used Terms

EPIDEMIOLOGY CHARACTERIZATION

SYNONYMS Scleredema adultorum of Buschke

INCIDENCE Probably more common than reported

AGE RANGE-MEDIAN Usually adult

GEOGRAPHY

CHINESE

Scleredema in Chinese patients: a local retrospective study and general review.

Leung CS, Chong LY.

Social Hygiene Service (Dermatology), Department of Health, Yung Fung Shee Social Hygiene Clinic, Cha Kwo Ling Road, Kowloon, Hong Kong.

Hong Kong Med J 1998 Mar;4(1):31-35 Abstract quote

The records from 12 Chinese adult patients with scleredema, who had attended the Social Hygiene Service of the Hong Kong Department of Health between 22 January 1990 and 19 March 1996, were retrieved and analysed.

The neck was the commonest site of involvement (75%), followed by the back (42%), and the shoulder (17%). The vast majority (83%) of scleredema cases were associated with diabetes mellitus; half of these were insulin-dependent. Most of the patients (92%) had hypertension for which medical treatment was needed. No cases of skin disease were preceded by acute infection, and none had any associated paraproteinaemia. The degree of skin involvement did not affect the daily activities of most of the patients.

This study revealed differences between the disease in our locality and those described in the western literature.

DISEASE ASSOCIATIONS CHARACTERIZATION

CHICKEN POX

Scleredema adultorum.

Parmar RC, Bavdekar SB, Bansal S, Doraiswamy A, Khambadkone S.

Department of Paediatrics, Seth G. S. Medical College and K. E. M. Hospital, Parel, Mumbai - 400 012, India.
J Postgrad Med 2000 Apr-Jun;46(2):91-3 Abstract quote
Scleredema adultorum is a rare connective tissue disorder reported usually following streptococcal infection, influenza, measles, and mumps. It has been reported occasionally following trauma and tuberculous lymphadenitis.

This is a report of scleredema adultorum developing after chicken pox in an eight-year-old male child. The diagnosis was established by characteristic picture on skin biopsy using special stain. The patient had a benign course and a spontaneous recovery in two weeks.

The case has been reported as the first case of scleredema adultorum developing after chicken pox.

DIABETES MELLITUS

A clinical observation of scleredema adultorum and its relationship to diabetes.

Rho YW, Suhr KB, Lee JH, Park JK.

Department of Dermatology, School of Medicine, Chungnam National University, Taejon, Korea.
J Dermatol 1998 Feb;25(2):103-7 Abstract quote
Scleredema may occur secondarily to diabetes or independently. The course of scleredema is not known in either type. Twenty-one scleredema patients were included in this study (13 females, 8 males).

The patients were divided into two groups according to the presence or absence of diabetes. In the group (11 patients) of scleredema which was secondary to diabetes, lesions were partially improved in 5 patients who had controlled diabetes, although it was difficult to control diabetes with insulin or oral hypoglycemics in such patients. Scleredema appeared insidiously in nine of these eleven patients. The posterior neck was involved, but the face was not. In patients without diabetes, the scleredema lesions began acutely in eight of ten of them.

The course of the disease was usually stationary rather than showing acute improvement. Facial involvement was found in half of all the patients. In conclusion, scleredema patients with diabetes may improve if their diabetes is controlled, and facial involvement may be related to scleredema without diabetes.

INFECTION

Scleredema revisited. A poststreptococcal complication.

Cron RQ, Swetter SM.

Department of Pediatrics, Lucille Salter Packard Children's Hospital at Stanford, California.
Clin Pediatr (Phila) 1994 Oct;33(10):606-10 Abstract quote
Scleredema is a rare connective disease which must be differentiated from scleroderma in childhood. Scleredema is characterized by thickening of the dermis of the neck, head, and upper trunk.

We report a case of scleredema in an 8-year-old boy with coincident streptococcal colonization. The patient report demonstrates many of the common features of scleredema, including an associated streptococcal infection, a relatively benign presentation of illness, and the characteristic mucopolysaccharide intradermal staining on skin biopsy. The literature on scleredema is reviewed, focusing on the disease course, differential diagnosis, and an overview of the proposed three subgroups of scleredema.

The association of scleredema to a prior streptococcal infection is explored, and a proposed autoimmune pathophysiology of the disease, as it relates to streptococcal infection, is presented.

NUCHAL FIBROMA

Nuchal fibroma associated with scleredema, diabetes mellitus and organic solvent exposure.

Banney LA, Weedon D, Muir JB.

Mater Misericordiae Hospital, South Brisbane, Australia.
Australas J Dermatol 2000 Feb;41(1):39-41 Abstract quote
A case of scleredema diabeticorum of Buschke associated with nuchal fibroma and organic solvent exposure is reported. The patient presented with a neck mass causing discomfort and restriction of movement.

Histological examination showed this to be a nuchal fibroma. Additionally, there was widespread induration of the skin of his trunk which was asymptomatic. A biopsy showed features of scleredema. This is the first reported association of these two conditions, both of which show increased and thickened collagen bundles without significant fibroblast proliferation. They differ by the occurrence of mucin in scleredema, although this is not always demonstrable, particularly in late lesions.

The possibility that nuchal fibroma is an end stage, localized form of scleredema is canvassed. The patient's medical history included insulin-dependent diabetes mellitus with complications of retinal vessel thrombosis and peripheral neuropathy. The patient also had significant past exposure to a wide variety of chemicals, including organic solvents.

PARAPROTEINEMIA

Systemic involvement in scleredema of Buschke associated with IgG-kappa paraproteinaemia.

Basarab T, Burrows NP, Munn SE, Russell Jones R.

Department of Dermatology, Ealing Hospital, Southall, Middlesex, UK.
Br J Dermatol 1997 Jun;136(6):939-42 Abstract quote
Scleredema is a rare primary cutaneous mucinosis. Systemic involvement is uncommon and histological confirmation is often lacking.

We report a case of a 60-year-old man with scleredema and evidence of mucin deposition on biopsies from multiple extracutaneous sites. The bone marrow, nerve, hepatic and salivary gland involvement seen on histology in our patient has not, to our knowledge, been previously reported in this condition.

RHEUMATOID ARTHRITIS

Scleredema of Buschke associated with rheumatoid arthritis and Sjogren's syndrome.

Miyagawa S, Dohi K, Tsuruta S, Shirai T.

Department of Dermatology, Nara Medical University, Japan.
Br J Dermatol 1989 Oct;121(4):517-20 Abstract quote
A case of scleredema of Buschke associated with rheumatoid arthritis and Sjogren's syndrome is described.

The onset of the skin changes and rheumatoid arthritis was almost simultaneous and the sicca syndrome developed 4 years later.

PATHOGENESIS CHARACTERIZATION

FIBROSIS

Scleredema and paraproteinemia. Enhanced collagen production and elevated type I procollagen messenger RNA level in fibroblasts grown from cultures from the fibrotic skin of a patient.

Oikarinen A, Ala-Kokko L, Palatsi R, Peltonen L, Uitto J.

Arch Dermatol 1987 Feb;123(2):226-9 Abstract quote
An edematous rash developed on the abdominal skin of a 76-year-old woman who had had diabetes mellitus for ten years. Some months later, the affected skin became thickened and indurated.

Histopathologic examination revealed marked dermal fibrosis with excessive deposition of collagen. The patient also had IgA (k-type) paraproteinemia. Fibroblast cultures from the affected and unaffected skin were studied for collagen metabolism. Procollagen synthesis was elevated about sixfold on fibroblasts derived from the affected skin. A similar increase was detected in messenger RNA (mRNA) levels using a complementary DNA clone specific for human pro alpha 1(l) collagen mRNA. The elevated mRNA level could be the result of increased transcriptional activity of collagen genes or decreased degradation of collagen mRNAs.

Our findings suggest that increased collagen deposition may account for the marked dermal fibrosis that we observed in this patient.

Scleredema adultorum: case report and demonstration of abnormal expression of extracellular matrix genes in skin fibroblasts in vivo and in vitro.

Varga J, Gotta S, Li L, Sollberg S, Di Leonardo M.

Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Br J Dermatol 1995 Jun;132(6):992-9 Abstract quote
To elucidate the mechanisms involved in the development of cutaneous fibrosis in scleredema adultorum, we studied a patient with long-standing scleredema who had no history of diabetes mellitus or preceding febrile illness.

Histological examination of a biopsy specimen from involved forearm skin demonstrated marked thickening of the dermis and accumulation of mucin between collagen bundles. Increased levels of type I collagen mRNA, as evidenced by positive in situ hybridization signals with an alpha 1(I) procollagen cDNA were found in numerous fibroblasts throughout the dermis. The expression of several genes coding for proteins involved in the maintenance of connective tissue was examined by determining in vitro protein production and mRNA levels in fibroblasts from the affected skin.

Total protein production, glucosamine incorporation and collagen synthesis, were elevated by 44-97% in scleredema fibroblasts, compared with fibroblasts from two healthy individuals. Levels of mRNAs for alpha 1(I) and alpha 1(III) procollagens and fibronectin were elevated in scleredema fibroblasts, whereas mRNA levels for the tissue inhibitor of metalloproteinase were unaltered compared with control cultures.

The results suggest that fibroblasts from the involved skin in non-diabetic patients with scleredema may exhibit a biosynthetically activated phenotype, which persists for several years. These alterations are likely to be involved in the development of the cutaneous induration and thickening which is characteristic of this disease.

Increased collagen propeptides in the skin of a scleredema patient but no change in re-epithelialisation rate.

Haapasaari KM, Kallioinen M, Tasanen K, Risteli J, Palatsi R, Oikarinen A.

Department of Dermatology, University of Oulu, Finland.
Acta Derm Venereol 1996 Jul;76(4):305-9 Abstract quote
Scleredema is a rare disease, affecting the skin connective tissue with increased amounts of collagen and glycosaminoglycans.

In the present study, the collagen synthesis and re-epithelialisation rate were measured from a 64-year-old male patient, who rapidly developed extensive tightening of the skin, without any underlying disease. The skin was thickened at several sites when measured with ultrasound, and the histology revealed accumulation of glycosaminoglycans and collagen bundles. The collagen synthesis rate was measured from suction blisters induced on two different sites of the skin before the treatment and three times later up to 6 months after the treatment with a systemic steroid was started.

The aminoterminal propeptide of type I collagen (PINP) was increased manifold in the affected skin when compared with the controls, indicating active collagen deposition in vivo. Systemic steroid medication with high doses (over 20 mg/d) decreased both the type I and the type III collagen propeptide levels. The time schedule of the decreases in the propeptides in the thickened, affected skin and in the clinically normal-looking skin varied, and especially in the thickened skin in the abdomen the decrease in PINP was noted only after 3 months of prednisolone therapy. When the prednisolone dose was only 10 mg daily, the propeptides were again up-regulated, perhaps reflecting the natural course of the disease. The re-epithelialisation rates at two different sites of the patient were similar to those in the controls, suggesting that even massive fibrosis with active deposition of collagen does not alter the basal rate of re-epithelialisation in the skin.

In conclusion, collagen synthesis is markedly elevated in scleredema, leading to fibrosis of the skin. A recently developed method utilizing assays of collagen propeptides from suction blister fluid allows monitoring of the collagen synthesis and detection of changes in the collagen synthesis during the treatment of fibrotic disorders.

GLYCOSAMINOGLYCANS

Diabetic scleredema: a case report and biochemical analysis for glycosaminoglycans.

Kobayashi T, Yamasaki Y, Watanabe T.

Division of Dermatology, Tokyo Daini National Hospital, Higashigaoka, Meguro, Japan.
J Dermatol 1997 Feb;24(2):100-3 Abstract quote
We report a patient with the typical lesions of diabetic scleredema. Histological findings of the involved skin were thickening of the dermis, depositions of mucins, and fibrosis. Biochemical analysis revealed an increase in glycosaminoglycans in the involved skin as well as in the cutaneous lupus mucinosis.

Mucinous materials were composed of hyaluronic acid.

SKIN MECHANICAL PROPERTIES

In vivo study of skin mechanical properties in scleredema of Buschke.

Dobrev H.

Department of Dermatology, Medical University, Plovdiv, Bulgaria.
Acta Derm Venereol 1998 Mar;78(2):103-6 Abstract quote
A non-invasive, in vivo suction device was used to investigate the mechanical properties of the skin in a patient with scleredema of Buschke.

Clinical scoring of skin induration and measurements of skin elasticity were performed over 9 anatomic regions on admission and after 3 (on discharge), 17 and 28 months. Immediate distension, final distension and immediate retraction were significantly decreased, while the viscoelastic to elastic ratio was significantly increased in the patient as compared to the healthy controls. Delayed distension and biological elasticity were preserved. Low values of skin distensibility correlated with a severe skin induration (p < 0.001). The changes were more expressive with the 8 mm-diameter measuring probe than the 2 mm-diameter probe.

The method applied can be used for objective and quantitative assessment of skin involvement in scleredema of Buschke.

LABORATORY/RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

RADIOLOGIC

The ultrasonic evaluation of skin thickness in scleredema.

Cole GW, Handler SJ, Burnett K.
J Clin Ultrasound 1981 Nov-Dec;9(9):501-3 Abstract quote
The skin thickness in a group of patients with scleredema was measured using ultrasonic techniques and then compared with a group of normal individuals.

The mean dermal thickness in scleredema was 7.7 mm, compared to 3.3 mm in the normal control group. Ultrasonic evaluation of skin thickness may be of value in following the natural history or response to therapy of certain diseases that affect dermal thickness.

Buschke's scleredema with right-sided heart failure. Echocardiographic and clinical observations.

Erlichman M, Glaser J.
Cardiology 1983;70(6):344-8 Abstract quote
Heart failure as a complication of Buschke's scleredema was not reported in the literature on this rare disease. A young girl with a severe form of Buschke's disease is described.

She developed severe right-sided heart failure--proven by the typical clinical, auscultatory, electrocardiographic and echocardiographic findings; was treated successfully with penicillin, anticongestive measures and steroids, and showed a remarkable complete recovery.

LABORATORY MARKERS

PARAPROTEINEMIA

Paraproteinemia in patients with scleredema. Clinical findings and serum effects on skin fibroblasts in vitro.

Ohta A, Uitto J, Oikarinen AI, Palatsi R, Mitrane M, Bancila EA, Seibold JR, Kim HC.

J Am Acad Dermatol 1987 Jan;16(1 Pt 1):96-107 Abstract quote
Four patients with paraproteinemia and scleredema were studied.

Histologic features included marked thickening and fibrosis of the dermis and subcutis. Variable amounts of mucin deposits were detected in the interfibrillar spaces. Serum from one patient significantly stimulated collagen production in normal skin fibroblast cultures, whereas serum from another patient stimulated collagen production in autologous cell cultures.

Moreover, serum from one patient stimulated the [35S]sulfate incorporation into the fibroblasts. Circulating serum factors, possibly related to the paraprotein, may enhance the synthesis of extracellular macromolecules by dermal fibroblasts in these patients, thus providing a mechanism for dermal fibrosis.

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

VARIANTS

CHILDHOOD

Scleroedema in a child.

Mitsuhashi Y, Kondo S, Shimizu Y.

Department of Dermatology, Yamagata University School of Medicine, Japan.
J Dermatol 1996 Jul;23(7):495-8 Abstract quote
A 3-year-old Japanese girl with scleroedema was reported. She had had no signs of diabetes but did have a preceding bacterial infection in the tonsils three weeks before the skin lesion appeared. The skin on the face, shoulders, extensor aspect of the upper arms, and proximal half of the forearms was indurated. The skin lesions expanded from the middle part of the forearms to the wrists during the observation period. Thereafter, the induration gradually disappeared.

A literature review revealed there were only six reports of scleroedema in children under 15 years old before 1996 in Japan; a total of 166 cases of the disease was reported in the same period. Five out of these six cases were not diabetes-associated. All but one of these six patients were female.

Juvenile scleroedema seems to be rare in Japan.

ESOPHAGUS

Scleredema adultorum of Buschke with upper esophageal involvement.

Wright RA, Bernie H.
Am J Gastroenterol 1982 Jan;77(1):9-11 Abstract quote
A 55-yr-old white female with biopsy proven scleredema adultorum was evaluated for progressive dysphagia.

Esophageal motility studies revealed persistently high upper esophageal pressures without response to deglutition, and minimal peristalsis in the upper body of the esophagus. A cine-esophagram revealed massive aspiration of barium into the nasopharynx and lungs, concommitant with stenosis in the upper esophagus.

The patient died presumptively from aspiration. This patient exemplifies a potentially lethal complication of scleredema adultorum i.e., upper esophageal infiltration with resultant aspiration.

HEART

Cardiomyopathy and multiple myeloma. Complications of scleredema adultorum.

Rimon D, Lurie M, Storch S, Halon D, Eisenkraft S, Laor A, Cohen L.

Department of Medicine B, Carmel Hospital, Haifa, Israel.
Arch Intern Med 1988 Mar;148(3):551-3 Abstract quote
Multiple myeloma and congestive heart failure developed in a patient with long-standing scleredema adultorum. Staining of the myocardium, performed after her death, was positive for acid mucopolysaccharide and negative for amyloid.

To the best of our knowledge, this is the first case in which acid mucopolysaccharide has been demonstrated in the myocardium, thus explaining the cardiomyopathy of scleredema adultorum. Review of the world literature enabled us to identify a statistically significant increased prevalence of plasma cell dyscrasia among patients with protracted scleredema.

In all patients, plasma cell dyscrasia appeared years after the onset of scleredema. Immunofluorescent studies were negative for immunoglobulin deposition. We assume, therefore, that the plasma cell dyscrasia was secondary to scleredema.

LOCALIZED

Scleredema diabeticorum of Buschke confined to the thighs.

Farrell AM, Branfoot AC, Moss J, Papadaki L, Woodrow DF, Bunker CB.

Department of Dermatology, Charing Cross and Westminster Medical School, London, U.K.
Br J Dermatol 1996 Jun;134(6):1113-5 Abstract quote
We describe a patient with insulin-dependent diabetes without vascular complications in whom scleredema was confined to the thighs.

Electron microscopy demonstrated heterogeneity in both the size and density of the collagen fibrils and the presence of filamentous material between them.

HISTOLOGICAL TYPES CHARACTERIZATION

GENERAL
Biopsy of the skin shows thickening of the reticular dermis with no fibroblast proliferation. There is minimal inflammation.

VARIANTS

SCLERODERMA-LIKE CHANGES

Diabetic scleredema and scleroderma-like changes in a patient with maturity onset type diabetes of young people.

Iwasaki T, Kohama T, Houjou S, Iriuchijima T, Ohtsuka T, Ishikawa T, Yamakage A, Mori M.

Department of Internal Medicine, University School of Medicine, Maebashi, Japan.
Dermatology 1994;188(3):228-31 Abstract quote
A 21-year-old housewife with maturity onset type diabetes of young people developed scleredema diabeticorum, scleroderma-like skin thickness on forearms and dorsum of hands, digital sclerosis and cheiroarthropathy. She had diabetes mellitus since the age of 11 years. Her grandfather on the mother's side, her mother and 3 of 5 her mother's brothers and sisters have diabetes mellitus. Blood glucose was 295 mg/dl. Urinary glucose was 5.3 g/day. Nail fold capillary microscopy revealed a progressive systemic sclerosis pattern.

Histologically, hematoxylin and eosin sections from back and forearm skin demonstrated broad collagen bundles separated by widened clear spaces throughout the thickened dermis.

SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHER CHARACTERIZATION

SPECIAL STAINS

Acid mucopolysaccharide staining in scleredema.

Cole HG, Winkelmann RK.

Department of Dermatology, Mayo Clinic, Rochester, MN 55905.
J Cutan Pathol 1990 Aug;17(4):211-3 Abstract quote
We studied 26 formalin-fixed biopsy specimens taken from 22 patients with scleredema and found positive staining in 67% of the tissues when both colloidal iron and alcian blue methods were used. Single stains were positive in only half the tissues.

Positive findings were noted in both patients with diabetes (11 patients) and in those without it (11 patients).

Our experience indicates that multiple biopsies may be necessary to demonstrate mucin in the dermis. Specimens obtained by incisional biopsy are preferred.

IMMUNOFLUORESCENCE

Scleredema adultorum of Buschke: a clinical, pathologic, and cell culture study of two patients.

Christy WC, Buckingham RB, Barnes EL, Prince RK.
J Rheumatol 1983 Aug;10(4):595-601 Abstract quote
Two patients with scleredema of Buschke are presented. The second patient developed scleredema after a febrile drug reaction. Biopsies of both involved and uninvolved skin were obtained for histologic examination and cell culture studies.

Immunofluorescent studies of the biopsy specimens revealed staining with IgG, IgM and C3 at the dermal-epidermal junction in the involved skin of the first patient. This has not been previously reported.

Cell culture studies revealed that fibroblasts from the involved skin produced more glycosaminoglycans (GAG) than uninvolved skin and most of the GAG produced was hyaluronic acid. Possible pathogenic mechanisms for this unusual condition are discussed.

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

PROGERIA

A case of Hutchinson-Gilford progeria syndrome mimicking scleredema in early infancy.

Erdem N, Gunes AT, Avci O, Osma E.

Department of Pediatrics, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey.
Dermatology 1994;188(4):318-21 Abstract quote
We report a case of Hutchinson-Gilford progeria syndrome (HGPS). The patient showed the characteristics of scleredema at the age of 2.5 months but developed all the manifestations of HGPS gradually until 10 months old.

The possibility of development of HGPS should by considered in any case of scleredema at birth or in early infancy.

PROGNOSIS AND TREATMENT CHARACTERIZATION

PROGNOSTIC FACTORS

GENERAL

Scleredema: a review of thirty-three cases.

Venencie PY, Powell FC, Su WP, Perry HO.
J Am Acad Dermatol 1984 Jul;11(1):128-34 Abstract quote
A review of thirty-three cases of scleredema, with particular reference to clinical and histologic findings, revealed that the disease was often of insidious onset and the course was usually prolonged. A preceding respiratory tract infection was uncommon and usually did not indicate a short course.

The patients were divided into two groups according to the presence or absence of diabetes. Diabetes, when present, was typically the late-onset, insulin-dependent type and difficult to control.

In many of these patients, the onset of scleredema was so subtle that it went unnoticed by the patient until pointed out by an examining physician.

A fatal case of scleredema of Buschke.

Sansom JE, Sheehan AL, Kennedy CT, Delaney TJ.

Department of Dermatology, Bristol Royal Infirmary, U.K.
Br J Dermatol 1994 May;130(5):669-70 Abstract quote
Scleredema of Buschke is a rare disorder characterized by the development of areas of skin induration which usually resolve spontaneously. It is occasionally associated with a benign gammopathy, and rarely with myelomatosis.

We describe a 60-year-old woman with extensive skin changes, who developed IgA myeloma. Unusually, her skin disease did not respond to conventional myeloma therapy. Death occurred as a consequence of the progressive skin disease.

Scleredema of Buschke: a report of seven cases.

Tate BJ, Kelly JW, Rotstein H.

Dermatology Unit, Alfred Hospital, Prahran, Vic, Australia.
Australas J Dermatol 1996 Aug;37(3):139-42 Abstract quote
Scleredema of Buschke is an uncommon dermatosis characterized by thickened, indurated skin, sometimes with erythema. Histopathology shows thickened dermal collagen with a mild infiltrate of mucin in the deeper dermis.

Seven adults with scleredema are presented, four females and three males, and their mean age at diagnosis was 54 years. All had diabetes mellitus for an average of 13 years prior to the onset of scleredema. Complications of diabetes, especially retinopathy (n = 5), neuropathy (n = 4) and peripheral vascular disease (n = 3), were present in five patients. One patient died (cause not established), and another has life-threatening cardiomyopathy.

We have no evidence that the scleredema was a significant aetiologic factor in either case, despite published reports of fatalities related to scleredema. Three patients were followed up for more than 1 year and, irrespective of therapy, the scleredema did not resolve in any patient.

TREATMENT

APHERESIS

Beneficial effect of aggressive low-density lipoprotein apheresis in a familial hypercholesterolemic patient with severe diabetic scleredema.

Koga N.

Division of Blood Purification, Department of Internal Medicine, Shin-Koga Hospital, Kurume, Japan.
Ther Apher 2001 Dec;5(6):506-12 Abstract quote
We present a 59-year-old woman with severe diabetic scleredema (DS) associated with heterozygous familial hypercholesterolemia (FH).

She had been treated with drugs to lower blood glucose, with insulin for diabetes mellitus (DM), and with low-density lipoprotein (LDL) apheresis therapy monthly or every 2 weeks in addition to drugs to lower serum lipids for FH. However, her scleredema had not improved. After we had tried weekly LDL apheresis therapy for a period of 3 years to treat her hyperlipidemia, the levels of her serum lipids were reduced to normal ranges, and scleredema in her nape improved.

We also demonstrated the histopathological improvement in dermis of her cervical skin. We conclude that weekly LDL apheresis therapy is effective for diabetic scleredema that is resistant to conventional treatments.

CHEMOTHERAPY

Improvement of scleredema associated with IgA multiple myeloma after chemotherapy.

Pujol JA, Bueno M, Fuertes MA, Gimenez H, Carapeto FJ.

Department of Dermatology, Hospital Clinico Universitario, Faculty of Medicine, Zaragoza, Spain.
Clin Exp Dermatol 1995 Mar;20(2):149-52 Abstract quote
The presence of a monoclonal gammopathy in patients with chronic scleredema is a recently described, unusual association of unknown significance. There have been very occasional reports of multiple myeloma in such patients.

We now report a patient with long-standing scleredema who developed an IgA-kappa multiple myeloma. Once chemotherapy for the myeloproliferative disorder was instituted, scleredema improved significantly, suggesting a pathogenetic link between the two conditions.

PHOTOPHERESIS

Scleredema associated with paraproteinaemia treated by extracorporeal photopheresis.
Stables GI, Taylor PC, Highet AS.

Department of Dermatology, The General Infirmary at Leeds, Leeds LS1 3EX, UK.
Br J Dermatol 2000 Apr;142(4):781-3 Abstract quote
Scleredema is a rare disease characterized by extensive cutaneous woody, non-pitting induration that spreads throughout the body.

We describe a patient with scleredema associated with paraproteinaemia who was successfully treated by extracorporeal photopheresis.

PROSTAGLANDINS

Severe diabetic scleredema with extension to the extremities and effective treatment using prostaglandin E1.

Ikeda Y, Suehiro T, Abe T, Yoshida T, Shinoki T, Tahara K, Nishiyama M, Okabayashi T, Nakamura T, Itoh H, Hashimoto K.

Second Department of Internal Medicine, Kochi Medical School, Nankoku.
Intern Med 1998 Oct;37(10):861-4 Abstract quote
We report a 49-year-old woman with severe diabetic scleredema (DS). The patient had non-insulin-dependent diabetes mellitus (NIDDM) for 9 years and noticed thickened skin on her back 3 years previously.

Her DS rapidly extended to her back and extremities with pain and immobility. Her symptoms of DS improved dramatically after establishing strict glycemic control and intravenous administration of prostaglandin E1 (PGE1). However, the histological findings of her skin biopsy did not change even after the treatment for 12 weeks, and her symptoms worsened again after discontinuation of glycemic control and PGE1 treatment. The causes of DS have been considered to be metabolic abnormalities associated with hyperglycemia and hypoxia in the skin due to diabetic microangiopathy. PGE1 was an effective treatment for DS in our patient.

Strict control of hyperglycemia and PGE1 treatment may be sufficient to manage DS, although a very long treatment period is necessary.

PUVA

Bath-PUVA therapy in three patients with scleredema adultorum.

Hager CM, Sobhi HA, Hunzelmann N, Wickenhauser C, Scharenberg R, Krieg T, Scharffetter-Kochanek K.

Department of Dermatology, University of Cologne, Germany.
J Am Acad Dermatol 1998 Feb;38(2 Pt 1):240-2 Abstract quote
BACKGROUND: Scleredema adultorum (SA) is a rare connective tissue disorder for which no treatment has proven to be effective.

OBJECTIVE: Our purpose was to determine the effect of bath-PUVA therapy on SA.

METHODS: Three patients were treated. Clinical evaluation of skin induration and thickness as well as ultrasonography were performed at baseline and after treatment.

RESULTS: All three patients showed substantial clinical improvement with bath-PUVA therapy (median of 59 treatments and a cumulative UVA dose of 245.7 J/cm2). Ultrasonography showed significant reduction in both skin thickness and density.

CONCLUSION: Bath-PUVA therapy appears to be effective in the treatment of SA.

RADIATION

Scleredema adultorum of buschke treated with radiation.

Bowen AR, Smith L, Zone JJ.

Departments of Dermatology and Radiation Oncology, University of Utah School of Medicine, Salt Lake City.
Arch Dermatol. 2003 Jun;139(6):780-4. Abstract quote
BACKGROUND: Scleredema adultorum of Buschke is an uncommon skin condition that may accompany diabetes mellitus. Current therapeutic options are poor, with only case reports and small series supporting their use.

Observation We describe 3 patients with severe restrictive scleredema associated with type 2 diabetes mellitus who responded to radiation therapy after other treatments had failed. Angle of shoulder abduction was used as an objective measurement of improvement, while the patients rated several subjective areas, including arm range of motion, ease of performing daily tasks, ease of breathing, and neck thickening. Objective improvement tended to plateau over time but remained well above baseline. The duration of subjective improvement was variable, lasting from a few months to the end of the observation time of 2(1/2) years.

Conclusion Though not consistently durable in its effect, radiation therapy appears to be a viable therapeutic option in extreme cases of this difficult-to-treat disease.

Dosimetric evaluation of a specialized radiotherapy treatment technique for scleredema.

Tobler M, Leavitt DD, Gibbs FA Jr.

University of Utah Health Science Center, Department of Radiation Oncology, Salt Lake City 84132, USA.
Med Dosim 2000 Winter;25(4):215-8 Abstract quote
Scleredema adultorum of Buschke is an unusual manifestation of diabetes mellitus that can result in painful indurations and thickening of the skin with associated limitation of motion, and has been previously reported to be responsive to radiotherapy.

We report on the method employed to treat a severely affected patient by means of opposed photon fields and multiple electron fields encompassing his entire neck, arms, and thorax.

Electron-beam therapy in scleredema adultorum with associated monoclonal hypergammaglobulinaemia.

Angeli-Besson C, Koeppel MC, Jacquet P, Andrac L, Sayag J.

Department of Dermatology, CHU la Timone, Marseille, France.
Br J Dermatol 1994 Mar;130(3):394-7 Abstract quote
We report a case of scleredema adultorum (Buschke's disease) associated with an IgA kappa monoclonal hypergammaglobulinaemia. A significant improvement in the skin was obtained with electron-beam therapy.

Scleredema would appear to be linked to monoclonal hypergammaglobulinaemia, but the relationship between the skin disorder and the immunoglobulin abnormality remains to be elucidated.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Commonly Used Terms

Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation

Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscope

Surgical Pathology Report
Examine an actual biopsy report to understand what each section means

Special Stains
Understand the tools the pathologist utilizes to aid in the diagnosis

How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate

Got Path?
Recent teaching cases and lectures presented in conferences

Internet Links

Last Updated 6/25/2003

DISEASE ASSOCIATIONS	CHARACTERIZATION
CHICKEN POX
Scleredema adultorum. Parmar RC, Bavdekar SB, Bansal S, Doraiswamy A, Khambadkone S. Department of Paediatrics, Seth G. S. Medical College and K. E. M. Hospital, Parel, Mumbai - 400 012, India.	J Postgrad Med 2000 Apr-Jun;46(2):91-3 Abstract quote Scleredema adultorum is a rare connective tissue disorder reported usually following streptococcal infection, influenza, measles, and mumps. It has been reported occasionally following trauma and tuberculous lymphadenitis. This is a report of scleredema adultorum developing after chicken pox in an eight-year-old male child. The diagnosis was established by characteristic picture on skin biopsy using special stain. The patient had a benign course and a spontaneous recovery in two weeks. The case has been reported as the first case of scleredema adultorum developing after chicken pox.
DIABETES MELLITUS
A clinical observation of scleredema adultorum and its relationship to diabetes. Rho YW, Suhr KB, Lee JH, Park JK. Department of Dermatology, School of Medicine, Chungnam National University, Taejon, Korea.	J Dermatol 1998 Feb;25(2):103-7 Abstract quote Scleredema may occur secondarily to diabetes or independently. The course of scleredema is not known in either type. Twenty-one scleredema patients were included in this study (13 females, 8 males). The patients were divided into two groups according to the presence or absence of diabetes. In the group (11 patients) of scleredema which was secondary to diabetes, lesions were partially improved in 5 patients who had controlled diabetes, although it was difficult to control diabetes with insulin or oral hypoglycemics in such patients. Scleredema appeared insidiously in nine of these eleven patients. The posterior neck was involved, but the face was not. In patients without diabetes, the scleredema lesions began acutely in eight of ten of them. The course of the disease was usually stationary rather than showing acute improvement. Facial involvement was found in half of all the patients. In conclusion, scleredema patients with diabetes may improve if their diabetes is controlled, and facial involvement may be related to scleredema without diabetes.
INFECTION
Scleredema revisited. A poststreptococcal complication. Cron RQ, Swetter SM. Department of Pediatrics, Lucille Salter Packard Children's Hospital at Stanford, California.	Clin Pediatr (Phila) 1994 Oct;33(10):606-10 Abstract quote Scleredema is a rare connective disease which must be differentiated from scleroderma in childhood. Scleredema is characterized by thickening of the dermis of the neck, head, and upper trunk. We report a case of scleredema in an 8-year-old boy with coincident streptococcal colonization. The patient report demonstrates many of the common features of scleredema, including an associated streptococcal infection, a relatively benign presentation of illness, and the characteristic mucopolysaccharide intradermal staining on skin biopsy. The literature on scleredema is reviewed, focusing on the disease course, differential diagnosis, and an overview of the proposed three subgroups of scleredema. The association of scleredema to a prior streptococcal infection is explored, and a proposed autoimmune pathophysiology of the disease, as it relates to streptococcal infection, is presented.
NUCHAL FIBROMA
Nuchal fibroma associated with scleredema, diabetes mellitus and organic solvent exposure. Banney LA, Weedon D, Muir JB. Mater Misericordiae Hospital, South Brisbane, Australia.	Australas J Dermatol 2000 Feb;41(1):39-41 Abstract quote A case of scleredema diabeticorum of Buschke associated with nuchal fibroma and organic solvent exposure is reported. The patient presented with a neck mass causing discomfort and restriction of movement. Histological examination showed this to be a nuchal fibroma. Additionally, there was widespread induration of the skin of his trunk which was asymptomatic. A biopsy showed features of scleredema. This is the first reported association of these two conditions, both of which show increased and thickened collagen bundles without significant fibroblast proliferation. They differ by the occurrence of mucin in scleredema, although this is not always demonstrable, particularly in late lesions. The possibility that nuchal fibroma is an end stage, localized form of scleredema is canvassed. The patient's medical history included insulin-dependent diabetes mellitus with complications of retinal vessel thrombosis and peripheral neuropathy. The patient also had significant past exposure to a wide variety of chemicals, including organic solvents.
PARAPROTEINEMIA
Systemic involvement in scleredema of Buschke associated with IgG-kappa paraproteinaemia. Basarab T, Burrows NP, Munn SE, Russell Jones R. Department of Dermatology, Ealing Hospital, Southall, Middlesex, UK.	Br J Dermatol 1997 Jun;136(6):939-42 Abstract quote Scleredema is a rare primary cutaneous mucinosis. Systemic involvement is uncommon and histological confirmation is often lacking. We report a case of a 60-year-old man with scleredema and evidence of mucin deposition on biopsies from multiple extracutaneous sites. The bone marrow, nerve, hepatic and salivary gland involvement seen on histology in our patient has not, to our knowledge, been previously reported in this condition.
RHEUMATOID ARTHRITIS
Scleredema of Buschke associated with rheumatoid arthritis and Sjogren's syndrome. Miyagawa S, Dohi K, Tsuruta S, Shirai T. Department of Dermatology, Nara Medical University, Japan.	Br J Dermatol 1989 Oct;121(4):517-20 Abstract quote A case of scleredema of Buschke associated with rheumatoid arthritis and Sjogren's syndrome is described. The onset of the skin changes and rheumatoid arthritis was almost simultaneous and the sicca syndrome developed 4 years later.

LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
The ultrasonic evaluation of skin thickness in scleredema. Cole GW, Handler SJ, Burnett K.	J Clin Ultrasound 1981 Nov-Dec;9(9):501-3 Abstract quote The skin thickness in a group of patients with scleredema was measured using ultrasonic techniques and then compared with a group of normal individuals. The mean dermal thickness in scleredema was 7.7 mm, compared to 3.3 mm in the normal control group. Ultrasonic evaluation of skin thickness may be of value in following the natural history or response to therapy of certain diseases that affect dermal thickness.
Buschke's scleredema with right-sided heart failure. Echocardiographic and clinical observations. Erlichman M, Glaser J.	Cardiology 1983;70(6):344-8 Abstract quote Heart failure as a complication of Buschke's scleredema was not reported in the literature on this rare disease. A young girl with a severe form of Buschke's disease is described. She developed severe right-sided heart failure--proven by the typical clinical, auscultatory, electrocardiographic and echocardiographic findings; was treated successfully with penicillin, anticongestive measures and steroids, and showed a remarkable complete recovery.
LABORATORY MARKERS
PARAPROTEINEMIA
Paraproteinemia in patients with scleredema. Clinical findings and serum effects on skin fibroblasts in vitro. Ohta A, Uitto J, Oikarinen AI, Palatsi R, Mitrane M, Bancila EA, Seibold JR, Kim HC.	J Am Acad Dermatol 1987 Jan;16(1 Pt 1):96-107 Abstract quote Four patients with paraproteinemia and scleredema were studied. Histologic features included marked thickening and fibrosis of the dermis and subcutis. Variable amounts of mucin deposits were detected in the interfibrillar spaces. Serum from one patient significantly stimulated collagen production in normal skin fibroblast cultures, whereas serum from another patient stimulated collagen production in autologous cell cultures. Moreover, serum from one patient stimulated the [35S]sulfate incorporation into the fibroblasts. Circulating serum factors, possibly related to the paraprotein, may enhance the synthesis of extracellular macromolecules by dermal fibroblasts in these patients, thus providing a mechanism for dermal fibrosis.

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
VARIANTS
CHILDHOOD
Scleroedema in a child. Mitsuhashi Y, Kondo S, Shimizu Y. Department of Dermatology, Yamagata University School of Medicine, Japan.	J Dermatol 1996 Jul;23(7):495-8 Abstract quote A 3-year-old Japanese girl with scleroedema was reported. She had had no signs of diabetes but did have a preceding bacterial infection in the tonsils three weeks before the skin lesion appeared. The skin on the face, shoulders, extensor aspect of the upper arms, and proximal half of the forearms was indurated. The skin lesions expanded from the middle part of the forearms to the wrists during the observation period. Thereafter, the induration gradually disappeared. A literature review revealed there were only six reports of scleroedema in children under 15 years old before 1996 in Japan; a total of 166 cases of the disease was reported in the same period. Five out of these six cases were not diabetes-associated. All but one of these six patients were female. Juvenile scleroedema seems to be rare in Japan.
ESOPHAGUS
Scleredema adultorum of Buschke with upper esophageal involvement. Wright RA, Bernie H.	Am J Gastroenterol 1982 Jan;77(1):9-11 Abstract quote A 55-yr-old white female with biopsy proven scleredema adultorum was evaluated for progressive dysphagia. Esophageal motility studies revealed persistently high upper esophageal pressures without response to deglutition, and minimal peristalsis in the upper body of the esophagus. A cine-esophagram revealed massive aspiration of barium into the nasopharynx and lungs, concommitant with stenosis in the upper esophagus. The patient died presumptively from aspiration. This patient exemplifies a potentially lethal complication of scleredema adultorum i.e., upper esophageal infiltration with resultant aspiration.
HEART
Cardiomyopathy and multiple myeloma. Complications of scleredema adultorum. Rimon D, Lurie M, Storch S, Halon D, Eisenkraft S, Laor A, Cohen L. Department of Medicine B, Carmel Hospital, Haifa, Israel.	Arch Intern Med 1988 Mar;148(3):551-3 Abstract quote Multiple myeloma and congestive heart failure developed in a patient with long-standing scleredema adultorum. Staining of the myocardium, performed after her death, was positive for acid mucopolysaccharide and negative for amyloid. To the best of our knowledge, this is the first case in which acid mucopolysaccharide has been demonstrated in the myocardium, thus explaining the cardiomyopathy of scleredema adultorum. Review of the world literature enabled us to identify a statistically significant increased prevalence of plasma cell dyscrasia among patients with protracted scleredema. In all patients, plasma cell dyscrasia appeared years after the onset of scleredema. Immunofluorescent studies were negative for immunoglobulin deposition. We assume, therefore, that the plasma cell dyscrasia was secondary to scleredema.
LOCALIZED
Scleredema diabeticorum of Buschke confined to the thighs. Farrell AM, Branfoot AC, Moss J, Papadaki L, Woodrow DF, Bunker CB. Department of Dermatology, Charing Cross and Westminster Medical School, London, U.K.	Br J Dermatol 1996 Jun;134(6):1113-5 Abstract quote We describe a patient with insulin-dependent diabetes without vascular complications in whom scleredema was confined to the thighs. Electron microscopy demonstrated heterogeneity in both the size and density of the collagen fibrils and the presence of filamentous material between them.

SPECIAL STAINS/IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
SPECIAL STAINS
Acid mucopolysaccharide staining in scleredema. Cole HG, Winkelmann RK. Department of Dermatology, Mayo Clinic, Rochester, MN 55905.	J Cutan Pathol 1990 Aug;17(4):211-3 Abstract quote We studied 26 formalin-fixed biopsy specimens taken from 22 patients with scleredema and found positive staining in 67% of the tissues when both colloidal iron and alcian blue methods were used. Single stains were positive in only half the tissues. Positive findings were noted in both patients with diabetes (11 patients) and in those without it (11 patients). Our experience indicates that multiple biopsies may be necessary to demonstrate mucin in the dermis. Specimens obtained by incisional biopsy are preferred.
IMMUNOFLUORESCENCE
Scleredema adultorum of Buschke: a clinical, pathologic, and cell culture study of two patients. Christy WC, Buckingham RB, Barnes EL, Prince RK.	J Rheumatol 1983 Aug;10(4):595-601 Abstract quote Two patients with scleredema of Buschke are presented. The second patient developed scleredema after a febrile drug reaction. Biopsies of both involved and uninvolved skin were obtained for histologic examination and cell culture studies. Immunofluorescent studies of the biopsy specimens revealed staining with IgG, IgM and C3 at the dermal-epidermal junction in the involved skin of the first patient. This has not been previously reported. Cell culture studies revealed that fibroblasts from the involved skin produced more glycosaminoglycans (GAG) than uninvolved skin and most of the GAG produced was hyaluronic acid. Possible pathogenic mechanisms for this unusual condition are discussed.

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
GENERAL
Scleredema: a review of thirty-three cases. Venencie PY, Powell FC, Su WP, Perry HO.	J Am Acad Dermatol 1984 Jul;11(1):128-34 Abstract quote A review of thirty-three cases of scleredema, with particular reference to clinical and histologic findings, revealed that the disease was often of insidious onset and the course was usually prolonged. A preceding respiratory tract infection was uncommon and usually did not indicate a short course. The patients were divided into two groups according to the presence or absence of diabetes. Diabetes, when present, was typically the late-onset, insulin-dependent type and difficult to control. In many of these patients, the onset of scleredema was so subtle that it went unnoticed by the patient until pointed out by an examining physician.
A fatal case of scleredema of Buschke. Sansom JE, Sheehan AL, Kennedy CT, Delaney TJ. Department of Dermatology, Bristol Royal Infirmary, U.K.	Br J Dermatol 1994 May;130(5):669-70 Abstract quote Scleredema of Buschke is a rare disorder characterized by the development of areas of skin induration which usually resolve spontaneously. It is occasionally associated with a benign gammopathy, and rarely with myelomatosis. We describe a 60-year-old woman with extensive skin changes, who developed IgA myeloma. Unusually, her skin disease did not respond to conventional myeloma therapy. Death occurred as a consequence of the progressive skin disease.
Scleredema of Buschke: a report of seven cases. Tate BJ, Kelly JW, Rotstein H. Dermatology Unit, Alfred Hospital, Prahran, Vic, Australia.	Australas J Dermatol 1996 Aug;37(3):139-42 Abstract quote Scleredema of Buschke is an uncommon dermatosis characterized by thickened, indurated skin, sometimes with erythema. Histopathology shows thickened dermal collagen with a mild infiltrate of mucin in the deeper dermis. Seven adults with scleredema are presented, four females and three males, and their mean age at diagnosis was 54 years. All had diabetes mellitus for an average of 13 years prior to the onset of scleredema. Complications of diabetes, especially retinopathy (n = 5), neuropathy (n = 4) and peripheral vascular disease (n = 3), were present in five patients. One patient died (cause not established), and another has life-threatening cardiomyopathy. We have no evidence that the scleredema was a significant aetiologic factor in either case, despite published reports of fatalities related to scleredema. Three patients were followed up for more than 1 year and, irrespective of therapy, the scleredema did not resolve in any patient.
TREATMENT
APHERESIS
Beneficial effect of aggressive low-density lipoprotein apheresis in a familial hypercholesterolemic patient with severe diabetic scleredema. Koga N. Division of Blood Purification, Department of Internal Medicine, Shin-Koga Hospital, Kurume, Japan.	Ther Apher 2001 Dec;5(6):506-12 Abstract quote We present a 59-year-old woman with severe diabetic scleredema (DS) associated with heterozygous familial hypercholesterolemia (FH). She had been treated with drugs to lower blood glucose, with insulin for diabetes mellitus (DM), and with low-density lipoprotein (LDL) apheresis therapy monthly or every 2 weeks in addition to drugs to lower serum lipids for FH. However, her scleredema had not improved. After we had tried weekly LDL apheresis therapy for a period of 3 years to treat her hyperlipidemia, the levels of her serum lipids were reduced to normal ranges, and scleredema in her nape improved. We also demonstrated the histopathological improvement in dermis of her cervical skin. We conclude that weekly LDL apheresis therapy is effective for diabetic scleredema that is resistant to conventional treatments.
CHEMOTHERAPY
Improvement of scleredema associated with IgA multiple myeloma after chemotherapy. Pujol JA, Bueno M, Fuertes MA, Gimenez H, Carapeto FJ. Department of Dermatology, Hospital Clinico Universitario, Faculty of Medicine, Zaragoza, Spain.	Clin Exp Dermatol 1995 Mar;20(2):149-52 Abstract quote The presence of a monoclonal gammopathy in patients with chronic scleredema is a recently described, unusual association of unknown significance. There have been very occasional reports of multiple myeloma in such patients. We now report a patient with long-standing scleredema who developed an IgA-kappa multiple myeloma. Once chemotherapy for the myeloproliferative disorder was instituted, scleredema improved significantly, suggesting a pathogenetic link between the two conditions.
PHOTOPHERESIS
Scleredema associated with paraproteinaemia treated by extracorporeal photopheresis. Stables GI, Taylor PC, Highet AS. Department of Dermatology, The General Infirmary at Leeds, Leeds LS1 3EX, UK.	Br J Dermatol 2000 Apr;142(4):781-3 Abstract quote Scleredema is a rare disease characterized by extensive cutaneous woody, non-pitting induration that spreads throughout the body. We describe a patient with scleredema associated with paraproteinaemia who was successfully treated by extracorporeal photopheresis.
PROSTAGLANDINS
Severe diabetic scleredema with extension to the extremities and effective treatment using prostaglandin E1. Ikeda Y, Suehiro T, Abe T, Yoshida T, Shinoki T, Tahara K, Nishiyama M, Okabayashi T, Nakamura T, Itoh H, Hashimoto K. Second Department of Internal Medicine, Kochi Medical School, Nankoku.	Intern Med 1998 Oct;37(10):861-4 Abstract quote We report a 49-year-old woman with severe diabetic scleredema (DS). The patient had non-insulin-dependent diabetes mellitus (NIDDM) for 9 years and noticed thickened skin on her back 3 years previously. Her DS rapidly extended to her back and extremities with pain and immobility. Her symptoms of DS improved dramatically after establishing strict glycemic control and intravenous administration of prostaglandin E1 (PGE1). However, the histological findings of her skin biopsy did not change even after the treatment for 12 weeks, and her symptoms worsened again after discontinuation of glycemic control and PGE1 treatment. The causes of DS have been considered to be metabolic abnormalities associated with hyperglycemia and hypoxia in the skin due to diabetic microangiopathy. PGE1 was an effective treatment for DS in our patient. Strict control of hyperglycemia and PGE1 treatment may be sufficient to manage DS, although a very long treatment period is necessary.
PUVA
Bath-PUVA therapy in three patients with scleredema adultorum. Hager CM, Sobhi HA, Hunzelmann N, Wickenhauser C, Scharenberg R, Krieg T, Scharffetter-Kochanek K. Department of Dermatology, University of Cologne, Germany.	J Am Acad Dermatol 1998 Feb;38(2 Pt 1):240-2 Abstract quote BACKGROUND: Scleredema adultorum (SA) is a rare connective tissue disorder for which no treatment has proven to be effective. OBJECTIVE: Our purpose was to determine the effect of bath-PUVA therapy on SA. METHODS: Three patients were treated. Clinical evaluation of skin induration and thickness as well as ultrasonography were performed at baseline and after treatment. RESULTS: All three patients showed substantial clinical improvement with bath-PUVA therapy (median of 59 treatments and a cumulative UVA dose of 245.7 J/cm2). Ultrasonography showed significant reduction in both skin thickness and density. CONCLUSION: Bath-PUVA therapy appears to be effective in the treatment of SA.
RADIATION
Scleredema adultorum of buschke treated with radiation. Bowen AR, Smith L, Zone JJ. Departments of Dermatology and Radiation Oncology, University of Utah School of Medicine, Salt Lake City.	Arch Dermatol. 2003 Jun;139(6):780-4. Abstract quote BACKGROUND: Scleredema adultorum of Buschke is an uncommon skin condition that may accompany diabetes mellitus. Current therapeutic options are poor, with only case reports and small series supporting their use. Observation We describe 3 patients with severe restrictive scleredema associated with type 2 diabetes mellitus who responded to radiation therapy after other treatments had failed. Angle of shoulder abduction was used as an objective measurement of improvement, while the patients rated several subjective areas, including arm range of motion, ease of performing daily tasks, ease of breathing, and neck thickening. Objective improvement tended to plateau over time but remained well above baseline. The duration of subjective improvement was variable, lasting from a few months to the end of the observation time of 2(1/2) years. Conclusion Though not consistently durable in its effect, radiation therapy appears to be a viable therapeutic option in extreme cases of this difficult-to-treat disease.
Dosimetric evaluation of a specialized radiotherapy treatment technique for scleredema. Tobler M, Leavitt DD, Gibbs FA Jr. University of Utah Health Science Center, Department of Radiation Oncology, Salt Lake City 84132, USA.	Med Dosim 2000 Winter;25(4):215-8 Abstract quote Scleredema adultorum of Buschke is an unusual manifestation of diabetes mellitus that can result in painful indurations and thickening of the skin with associated limitation of motion, and has been previously reported to be responsive to radiotherapy. We report on the method employed to treat a severely affected patient by means of opposed photon fields and multiple electron fields encompassing his entire neck, arms, and thorax.
Electron-beam therapy in scleredema adultorum with associated monoclonal hypergammaglobulinaemia. Angeli-Besson C, Koeppel MC, Jacquet P, Andrac L, Sayag J. Department of Dermatology, CHU la Timone, Marseille, France.	Br J Dermatol 1994 Mar;130(3):394-7 Abstract quote We report a case of scleredema adultorum (Buschke's disease) associated with an IgA kappa monoclonal hypergammaglobulinaemia. A significant improvement in the skin was obtained with electron-beam therapy. Scleredema would appear to be linked to monoclonal hypergammaglobulinaemia, but the relationship between the skin disorder and the immunoglobulin abnormality remains to be elucidated.

Clinical Presentation	Description
Acute	Occurs after a few days or weeks following a febrile illness caused by streptococcus or a virus
Insidious	No preceeding illness Protracted course
Insidious and prolonged	Associated with insulin dependent diabetes mellitus

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis and Treatment
Commonly Used Terms

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	Scleredema adultorum of Buschke
INCIDENCE	Probably more common than reported
AGE RANGE-MEDIAN	Usually adult
GEOGRAPHY
CHINESE
Scleredema in Chinese patients: a local retrospective study and general review. Leung CS, Chong LY. Social Hygiene Service (Dermatology), Department of Health, Yung Fung Shee Social Hygiene Clinic, Cha Kwo Ling Road, Kowloon, Hong Kong.	Hong Kong Med J 1998 Mar;4(1):31-35 Abstract quote The records from 12 Chinese adult patients with scleredema, who had attended the Social Hygiene Service of the Hong Kong Department of Health between 22 January 1990 and 19 March 1996, were retrieved and analysed. The neck was the commonest site of involvement (75%), followed by the back (42%), and the shoulder (17%). The vast majority (83%) of scleredema cases were associated with diabetes mellitus; half of these were insulin-dependent. Most of the patients (92%) had hypertension for which medical treatment was needed. No cases of skin disease were preceded by acute infection, and none had any associated paraproteinaemia. The degree of skin involvement did not affect the daily activities of most of the patients. This study revealed differences between the disease in our locality and those described in the western literature.

HISTOLOGICAL TYPES	CHARACTERIZATION
GENERAL	Biopsy of the skin shows thickening of the reticular dermis with no fibroblast proliferation. There is minimal inflammation.
VARIANTS
SCLERODERMA-LIKE CHANGES
Diabetic scleredema and scleroderma-like changes in a patient with maturity onset type diabetes of young people. Iwasaki T, Kohama T, Houjou S, Iriuchijima T, Ohtsuka T, Ishikawa T, Yamakage A, Mori M. Department of Internal Medicine, University School of Medicine, Maebashi, Japan.	Dermatology 1994;188(3):228-31 Abstract quote A 21-year-old housewife with maturity onset type diabetes of young people developed scleredema diabeticorum, scleroderma-like skin thickness on forearms and dorsum of hands, digital sclerosis and cheiroarthropathy. She had diabetes mellitus since the age of 11 years. Her grandfather on the mother's side, her mother and 3 of 5 her mother's brothers and sisters have diabetes mellitus. Blood glucose was 295 mg/dl. Urinary glucose was 5.3 g/day. Nail fold capillary microscopy revealed a progressive systemic sclerosis pattern. Histologically, hematoxylin and eosin sections from back and forearm skin demonstrated broad collagen bundles separated by widened clear spaces throughout the thickened dermis.