eMedicine Specialties > Dermatology > Connective Tissue Diseases

Scleredema

Misha A Rosenbach, MD, Staff Physician, Departments of Medicine and Dermatology, Hospital of the University of Pennsylvania
Victoria P Werth, MD, Professor of Dermatology and Medicine, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, Philadelphia Veterans Administration Hospital; Dina D Strachan, MD, Assistant Clinical Professor, Department of Dermatology, St Vincent's Medical Center

Updated: Oct 7, 2008

Introduction

Background

Scleredema is an uncommon condition of unknown etiology. Scleredema is characterized by a nonpitting induration of the skin with occasional erythema. Scleredema may be associated with a history of an antecedent febrile illness, diabetes mellitus, or blood dyscrasia. Although regarded as a benign, self-limited, skin disease, scleredema may be persistent and involve the viscera. Rarely, it may result in death.

The term scleredema is a misnomer because neither sclerosis nor edema is found on microscopic examination. The histologic findings of scleredema include deposition of mucin between dermal collagen bundles. The deposition is greatest in the deep dermis.

The Medscape CME course Progressive Arm and Leg Stiffness in a Patient With Chronic Renal Impairment may be of interest.

Pathophysiology

The etiology of scleredema is unknown. Scleredema localized to the back is commonly associated with diabetes mellitus, while generalized scleredema may follow a viral illness. Comparative quantitative polymerase chain reaction (PCR) analysis of lesional and nonlesional skin in patients with scleredema has demonstrated an increase in collagen gene expression in affected sites.¹ Fibroblast culture of affected scleredema skin has shown increased procollagen synthesis. Likewise, serum from patients with scleredema has been shown to stimulate collagen production in normal skin fibroblasts.

Frequency

United States

Scleredema is rare, although diabetes-related scleredema is likely underreported.

International

Scleredema is rare.

Mortality/Morbidity

• The morbidity of the skin changes of scleredema depends on the area of the body involved. Involvement of the skin over the joints may cause limited range of motion. Scleredema on the face can result in difficulty in opening the eyes and the mouth. Although rare, extensive truncal involvement may cause restrictive lung disease; one case of fatal scleredema was attributed to pneumonia developing secondary to extensive stiffness of the upper torso as a result of progressive scleredema.² Reports of recurrent cellulitis and delayed wound healing in areas of affected skin also exist.
• Unlike scleroderma, the tongue may be involved in scleredema, resulting in dysarthria and difficulty with mastication and tongue protrusion.
• Cardiac involvement in scleredema patients is rare and may result in cardiomyopathy,³ heart failure, arrhythmias, pericardial effusion, and unexplained murmurs.
• Other organs that may be involved in scleredema include skeletal muscles, ocular muscles, the pharynx, the liver, parotid glands, pleurae, the peritoneum, and the spleen.
• One case report describes scleredema limited to the periorbital region, which led to partial vision blockage.⁴
• Esophageal involvement is usually thought to be a feature that distinguishes scleredema, which does not affect the esophagus, from scleroderma, which does affect it. In one report, a patient developed dysphagia presumably from scleredema of the upper part of the esophagus. Esophageal biopsy was not performed on this patient.⁵
• Death from scleredema is uncommon. However, reports have described patients dying from the complications of visceral involvement and from extensive skin disease.

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, except in the type associated with adult-onset diabetes, which is more common in men than in women.

Age

Scleredema occurs in individuals of all ages.⁶ Although scleredema is sometimes referred to as scleredema adultorum, 50% of scleredema cases occur in individuals younger than 20 years.

Clinical

History

• The initial skin changes of scleredema occur on the face, the neck, or the upper part of the back. Patients may report difficulty in smiling, in opening their mouths, and in wrinkling their foreheads. They may have limited range of motion. The skin changes tend to spread distally, and they are usually confined to the upper part of the body. However, a case of scleredema localized on the thighs has been reported.⁷ Hands and feet are typically spared. Scleredema patients with tongue involvement may report dysarthria.
• Scleredema can be categorized into 3 clinical subgroups. Each has a different history, course, and prognosis.
  • Group 1 includes scleredema after acute respiratory infection (scleredema adultorum). Patients in group 1 have a history of a preceding febrile illness, particularly an upper respiratory tract streptococcal infection. The onset of the skin lesions is rapid, and the condition usually clears spontaneously in 6 months to 2 years. The duration is not affected by the use of antibiotics. The term scleredema adultorum is considered by some to be a misnomer because most pediatric patients fall into this group.
  • Group 2 includes scleredema patients whose disease tends to occur insidiously, with no preceding illness. This group encompasses cases associated with a monoclonal gammopathy.
  • Group 3 is scleredema associated with diabetes mellitus (scleredema diabeticorum) and includes patients with preexisting diabetes, which is typically adult in onset and often type 1. This disorder tends to occur more often in males, and this subgroup of patients typically experiences a more protracted course that is refractory to therapy. As in group 2, the onset of skin lesions is insidious. The upper back typically demonstrates erythema and induration. A pebbled appearance may evolve.

Physical

• Primary lesion
  • The lesions of scleredema are ill-defined, woody, nonpitting, indurated plaques. Generalized cases may clinically mimic edema.
  • Erythema, hyperpigmentation, and/or a peau d'orange appearance of the affected areas may be present.
  • The epidermis overlying the indurated areas wrinkles when pinched.
• Distribution
  • Scleredema is usually most evident in the upper part of the body, specifically the face, the neck, the trunk, and the extremities. However, a case of scleredema confined to the thighs has been reported.⁷
  • Hands and feet are typically spared in scleredema.
  • Scleredema patients with extensive facial involvement may appear expressionless and may have difficulty in opening their mouths.
  • Scleredema patients may have difficulty with tongue protrusion. These patients may also report dysarthria. Tongue involvement helps distinguish scleredema from scleroderma, which never affects the tongue.
• Color: Affected skin may be flesh-colored, erythematous, or hyperpigmented.

Causes

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.

• Febrile illness
  • Streptococcal infections^8,9 : An upper respiratory tract infection (typically pharyngitis) is the most common cause of scleredema in patients in group 1.
  • Other infections: The onset of scleredema has also been associated with cytomegalovirus, influenza, measles, pertussis, mumps, diphtheria, typhus fever, encephalitis, and dental abscesses.
• Trauma: Rare reports exist of scleredema occurring after trauma to the affected area. One report has described geometric scleredema due to mechanical stress.¹⁰
• Myelomatous disorders^11,12 : A subset of patients in group 2 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.
• Diabetes mellitus^13,14 : Patients usually have a long-standing history of diabetes, which tends to be type 1 and difficult to control. Diabetes-associated scleredema persists indefinitely and is unaffected by insulin therapy.

Differential Diagnoses

Amyloidosis, Primary Systemic
Cellulitis
Dermatomyositis
Morphea
Sclerema Neonatorum
Subcutaneous Fat Necrosis of the Newborn

Other Problems to Be Considered

Edema of cardiac and renal diseases
Lymphedema
Myxedema
Scleroderma

Workup

Laboratory Studies

• A throat culture should be obtained in scleredema patients to exclude group A streptococcal infection.
• Antistreptolysin-O (ASO) titers should be obtained in scleredema patients to exclude a recent infection with group A streptococci in a patient without clinically apparent pharyngitis or other infectious etiology.
• Fasting blood glucose or glycosylated hemoglobin measurements should be obtained in scleredema patients to rule out diabetes mellitus.
• Serum protein electrophoresis (SPEP) should be performed in scleredema patients to exclude a monoclonal gammopathy. Immunoglobulin G (IgG) paraproteinemias and multiple myelomas have been reported in patients with scleredema (group 2). Blood dyscrasias usually appear several years after the onset of scleredema. The median interval between diagnosis of scleredema and the detection of paraprotein has been reported as 2.5 years; in some cases, the detection of paraproteinemia occurred before or concurrent with the diagnosis of scleredema.

Imaging Studies

• Some investigators have proposed ultrasonic imaging of skin thickness in scleredema patients as a method to monitor the response to therapy.

Other Tests

• Skin biopsy should be performed in scleredema patients. The diagnosis of scleredema must be confirmed with histopathologic examination of the skin.

Histologic Findings

Although scleredema has some distinctive clinical features, a biopsy should be performed to confirm the diagnosis. Punch biopsy or incisional biopsy in scleredema patients should include the subcutaneous fat. The histopathologic analysis reveals a normal epidermis with a thickened dermis and increased spaces between large collagen bundles. The space results from increased deposition of mucopolysaccharide (hyaluronic acid) in the dermis. The mucin is more prominent in the deep dermis. In some cases in scleredema patients, mucin is better detected in unfixed sections stained at a pH of 7.0 with toluidine blue or in tissue fixed with 0.05% or 1% cetylpyridinium chloride solution and stained with Alcian blue at a pH of 2.5. Appendiceal structures in scleredema remain unchanged (unlike scleroderma).

Treatment

Medical Care

• Appropriate antibiotic therapy should be started in scleredema patients if infection is detected, although antibiotics do not appear to shorten the course of skin findings in scleredema.
• Evaluation and treatment for blood dyscrasias and diabetes mellitus should be completed in scleredema patients.
• Case reports in scleredema patients also describe scleredema occurring in association with internal malignancies (eg, carcinoma of the gall bladder,¹⁵ malignant insulinoma¹⁶ ). Imaging studies are warranted if this is suggested based on clinical findings.
• Rare reports describe scleredema following scabies infestation; appropriate evaluation for possible antecedent infestation may be warranted.¹⁷
• 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.¹⁸

Consultations

• Internal medicine or pediatrics specialist
  • Refer individuals for further evaluation and management in cases of detected blood dyscrasias and/or monoclonal gammopathies.
  • Refer patients with diabetes mellitus–associated scleredema, although most of these patients have diabetes that has been present for years before the onset of scleredema.
• Physical therapist
  • Refer patients with range of motion difficulties.
  • Prompt attention to physical therapy can potentially reduce long-term range of motion limitations.

Diet

No restrictions are necessary.

Activity

No restrictions are necessary.

Medication

No therapy is consistently effective for scleredema. A number of therapies, including systemic steroids, cyclosporine,¹⁹ methotrexate, high-dose penicillin,¹⁴ UVA1 phototherapy,²⁰ psoralen with ultraviolet light A (PUVA) either administered systemically or via cream²¹ or bath therapy,²² penicillamine, electron beam,^11,23 and glycemic control with prostaglandin E ₁ (PGE ₁ ),¹³ have all been tried with limited success.

In cases associated with myeloma, chemotherapy directed at the hematologic malignancy has been reported to result in concomitant improvement of the skin disease.¹⁶ For patients with paraproteinemia, extracorporeal photophoresis has been used.²⁴

Follow-up

Further Outpatient Care

• Patients with long-standing scleredema should be periodically monitored using the results of serum protein and immunoprotein electrophoresis to detect the development of paraproteinemia or myeloma. Blood dyscrasias may occur several years after the onset of scleredema.

Complications

• Complications include the following:
  • Limited range of motion
  • Poor wound healing
  • Recurrent skin infections
  • Restrictive lung disease
  • Dysarthria
  • Dysphagia
  • Difficulty in closing the eyes
  • Death (rare)

Prognosis

• The course of scleredema is unpredictable.
  • Patients in group 1, 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 in groups 2 and 3 typically have a slowly progressive or unremitting course over many years.
  • Reports of relapses following apparent improvement also exist.

Multimedia

Media file 1: Middle-aged man who has diabetes with scleredema on the upper part of the back.

Media file 2: Middle-aged man who has diabetes with scleredema on the upper part of the back. A close-up of the same patient as in Image 1.

References

1. Tasanen K, Palatsi R, Oikarinen A. Demonstration of increased levels of type I collagen mRNA using quantitative polymerase chain reaction in fibrotic and granulomatous skin diseases. Br J Dermatol. Jul 1998;139(1):23-6. [Medline].

2. Sansom JE, Sheehan AL, Kennedy CT, Delaney TJ. A fatal case of scleredema of Buschke. Br J Dermatol. May 1994;130(5):669-70. [Medline].

3. Rimon D, Lurie M, Storch S, Halon D, Eisenkraft S, Laor A, et al. Cardiomyopathy and multiple myeloma. Complications of scleredema adultorum. Arch Intern Med. Mar 1988;148(3):551-3. [Medline].

4. Ioannidou DI, Krasagakis K, Stefanidou MP, Karampekios S, Panayiotidis J, Tosca AD. Scleredema adultorum of Buschke presenting as periorbital edema: a diagnostic challenge. J Am Acad Dermatol. Feb 2005;52(2 Suppl 1):41-4. [Medline].

5. Wright RA, Bernie H. Scleredema adultorum of Buschke with upper esophageal involvement. Am J Gastroenterol. Jan 1982;77(1):9-11. [Medline].

6. Heilbron B, Saxe N. Scleredema in an infant. Arch Dermatol. Dec 1986;122(12):1417-9. [Medline].

7. Farrell AM, Branfoot AC, Moss J, Papadaki L, Woodrow DF, Bunker CB. Scleredema diabeticorum of Buschke confined to the thighs. Br J Dermatol. Jun 1996;134(6):1113-5. [Medline].

8. Alp H, Orbak Z, Aktas A. Scleredema adultorum due to streptococcal infection. Pediatr Int. Feb 2003;45(1):101-3. [Medline].

9. Cron RQ, Swetter SM. Scleredema revisited. A poststreptococcal complication. Clin Pediatr (Phila). Oct 1994;33(10):606-10. [Medline].

10. Tsunemi Y, Ihn H, Fujita H, Asashima N, Saeki H, Tamaki K. Square-shaped scleredema in the back: probably induced by mechanical stress. Int J Dermatol. Sep 2005;44(9):769-70. [Medline].

11. Angeli-Besson C, Koeppel MC, Jacquet P, Andrac L, Sayag J. Electron-beam therapy in scleredema adultorum with associated monoclonal hypergammaglobulinaemia. Br J Dermatol. Mar 1994;130(3):394-7. [Medline].

12. McFadden N, Ree K, Søyland E, Larsen TE. Scleredema adultorum associated with a monoclonal gammopathy and generalized hyperpigmentation. Arch Dermatol. May 1987;123(5):629-32. [Medline].

13. Ikeda Y, Suehiro T, Abe T, Yoshida T, Shinoki T, Tahara K, et al. Severe diabetic scleredema with extension to the extremities and effective treatment using prostaglandin E1. Intern Med. Oct 1998;37(10):861-4. [Medline].

14. Krasagakis K, Hettmannsperger U, Trautmann C, Tebbe B, Garbe C. Persistent scleredema of Buschke in a diabetic: improvement with high-dose penicillin. Br J Dermatol. Mar 1996;134(3):597-8. [Medline].

15. Manchanda Y, Das S, Sharma VK, Srivastava DN. Scleredema associated with carcinoma of the gall bladder. Br J Dermatol. Jun 2005;152(6):1373-4. [Medline].

16. Santos-Juanes J, Osuna CG, Iglesias JR, De Quiros JF, del Río JS. Treatment with chemotherapy of scleredema associated with Ig A myeloma. Int J Dermatol. Nov 2001;40(11):720-1. [Medline].

17. Malhotra AK, Sethuraman G, Das AK, Sharma VK. Scleredema following scabies infestation. Pediatr Dermatol. Jan-Feb 2008;25(1):136-8. [Medline].

18. Ranganathan P. Infliximab-induced scleredema in a patient with rheumatoid arthritis. J Clin Rheumatol. Dec 2005;11(6):319-22. [Medline].

19. Mattheou-Vakali G, Ioannides D, Thomas T, Lazaridou E, Tsogas P, Minas A. Cyclosporine in scleredema. J Am Acad Dermatol. Dec 1996;35(6):990-1. [Medline].

20. Eberlein-König B, Vogel M, Katzer K, Hein R, Köhn FM, Ring J, et al. Successful UVA1 phototherapy in a patient with scleredema adultorum. J Eur Acad Dermatol Venereol. Mar 2005;19(2):203-4. [Medline].

21. Grundmann-Kollmann M, Ochsendorf F, Zollner TM, Spieth K, Kaufmann R, Podda M. Cream PUVA therapy for scleredema adultorum. Br J Dermatol. May 2000;142(5):1058-9. [Medline].

22. Hager CM, Sobhi HA, Hunzelmann N, Wickenhauser C, Scharenberg R, Krieg T, et al. Bath-PUVA therapy in three patients with scleredema adultorum. J Am Acad Dermatol. Feb 1998;38(2 Pt 1):240-2. [Medline].

23. Tamburin LM, Pena JR, Meredith R, Soong VY. Scleredema of Buschke successfully treated with electron beam therapy. Arch Dermatol. Apr 1998;134(4):419-22. [Medline].

24. Stables GI, Taylor PC, Highet AS. Scleredema associated with paraproteinaemia treated by extracorporeal photopheresis. Br J Dermatol. Apr 2000;142(4):781-3. [Medline].

25. Basarab T, Burrows NP, Munn SE, Russell Jones R. Systemic involvement in scleredema of Buschke associated with IgG-kappa paraproteinaemia. Br J Dermatol. Jun 1997;136(6):939-42. [Medline].

26. Bowen AR, Smith L, Zone JJ. Scleredema adultorum of Buschke treated with radiation. Arch Dermatol. Jun 2003;139(6):780-4. [Medline].

27. Curtis AC, Shulak BM. Scleredema adultorum. Not always a benign self-limited disease. Arch Dermatol. Nov 1965;92(5):526-41. [Medline].

28. Dziadzio M, Anastassiades CP, Hawkins PN, Potter M, Gabrielli A, Brough GM, et al. From scleredema to AL amyloidosis: disease progression or coincidence? Review of the literature. Clin Rheumatol. Feb 2006;25(1):3-15. [Medline].

29. Maize J, Metcalf J. Metabolic diseases of the skin. In: Lever WF, Elenitsas R, Jaworsky C, Johnson B, eds. Lever's Histopathology of the Skin. 8^th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1997.

30. Rees R, Moore A, Nanney L, King L. Scleredema adultorum: the surgical implications of a rare dermatologic disorder. Plast Reconstr Surg. Jul 1983;72(1):90-3. [Medline].

31. Roupe G, Laurent TC, Malmström A, Suurküla M, Särnstrand B. Biochemical characterization and tissue distribution of the scleredema in a case of Buschke's disease. Acta Derm Venereol. 1987;67(3):193-8. [Medline].

32. Saunders M, Herzberg A, McCarthy DJ. Scleredema of Buschke of the lower extremity. J Am Podiatr Med Assoc. Sep 1986;76(9):496-501. [Medline].

33. Schmults CA. Scleroderma. Dermatol Online J. Oct 2003;9(4):11. [Medline].

34. Varga J, Gotta S, Li L, Sollberg S, Di Leonardo M. Scleredema adultorum: case report and demonstration of abnormal expression of extracellular matrix genes in skin fibroblasts in vivo and in vitro. Br J Dermatol. Jun 1995;132(6):992-9. [Medline].

35. Verghese A, Noble J, Diamond RD. Scleredema adultorum. A case of the recurrent cellulitis syndrome. Arch Dermatol. Nov 1984;120(11):1518-9. [Medline].

Keywords

scleredema adultorum, scleredema adultorum of Buschke, scleredema diabeticorum, scleredema diabeticorum of Buschke

Contributor Information and Disclosures

Author

Misha A Rosenbach, MD, Staff Physician, Departments of Medicine and Dermatology, Hospital of the University of Pennsylvania
Misha A Rosenbach, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Coauthor(s)

Victoria P Werth, MD, Professor of Dermatology and Medicine, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, Philadelphia Veterans Administration Hospital
Victoria P Werth, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, American College of Rheumatology, Medical Dermatology Society, Phi Beta Kappa, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Dina D Strachan, MD, Assistant Clinical Professor, Department of Dermatology, St Vincent's Medical Center
Dina D Strachan, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Susan M Swetter, MD, Director, Pigmented Lesion and Cutaneous Melanoma Clinic, Associate Professor, Department of Dermatology, Stanford University Medical Center, Veterans Affairs Palo Alto Health Care System
Susan M Swetter, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society of Clinical Oncology, Eastern Cooperative Oncology Group, Pacific Dermatologic Association, Society for Investigative Dermatology, and Women's Dermatologic Society
Disclosure: Schering Plough Honoraria Speaking and teaching

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Lester F Libow, MD, Dermatopathologist, South Texas Dermatopathology Laboratory
Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Texas Medical Association
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

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