Scleredema

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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:

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:

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:

Death from scleredema is rare. However, reports have described patients dying from the complications of cardiac or respiratory involvement.[13, 24]

History

Patients report stiff or hard skin. The rapidity of onset and locations of involvement differ based on the clinical subgroup. A thorough history regarding preceding illnesses, history of diabetes, and a review of systems should be performed to help identify less commonly associated extracutaneous manifestations (lungs, heart, trouble eating or talking, or muscle weakness) or, rarely, reported associations with malignancies.

Scleredema can be categorized into three clinical subgroups. Each has a different history, course, and prognosis. Note the following:

Type 1, postinfectious

This subgroup was historically referred to as scleredema adultorum. However, this is considered by some to be a misnomer because most pediatric patients fall into this group. Patients report a hardening of the skin a few weeks after a febrile illness, most commonly an upper or lower respiratory tract streptococcal infection.[25] The skin hardening progresses rapidly, first involving the face and neck, then spreading distally to involve the trunk and proximal upper limbs in a symmetric manner. Hands and feet are typically spared. Complications may include difficulty in smiling, opening the mouth, limited range of motion, and, in severe cases, involvement of the pharynx or tongue can lead to dysphagia or dysphonia. The condition usually clears spontaneously in 6 months to 2 years. The duration is not affected by the use of antibiotics.

Type 2, associated plasma dyscrasia

This subgroup includes patients whose disease tends to occur insidiously, progressing slowly over many years, with no history of preceding illness. Rimon et al identified 52 cases of type 2 scleredema in the world literature from 1963 to 1986, of which 25% had plasma cell dyscrasias, including 3 with multiple myeloma and 10 with monoclonal gammopathy of unknown significance. They also noted that the gammopathies were diagnosed on average 10 years after the onset of scleredema skin changes.[13] IgG monoclonal gammopathy is most common, followed by an IgA type. Spontaneous remission is much less likely to occur than in the type 1 subgroup.

Type 3, associated diabetes mellitus (scleredema diabeticorum)

This subtype of scleredema tends to occur more often in middle-aged males (at a reported 10:1 ratio), often obese, with longstanding, often uncontrolled, diabetes mellitus. In a 2015 multicenter study, 30 (68%) of 44 patients with scleredema had poorly controlled diabetes, with a type 2‒to‒type 1 ratio of 6.5:1.[26] Subtle skin hardening of the upper back begins in an insidious manner, progressing slowly over many years, to involve the upper back, neck, and shoulders with associated erythema; often, a pebbled appearance may evolve. Patients typically experience a more protracted course that is refractory to therapy. Control of the hyperglycemia does not improve the scleredema.[27]

Physical Examination

Scleredema presents as 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 taught skin may appear shiny, and, when pinched, firmness is appreciated with noted wrinkling of overlying epidermis.

Scleredema is usually most evident in the upper part of the body, specifically the face, the neck, the trunk, and the extremities in type 1 and 2 subgroups. However, a case of scleredema confined to the thighs[28] and a case of scleredema confined to the periocular region[29] have been reported. Hands and feet are typically spared in scleredema, in contrast to systemic sclerosis, which has sclerodactyly. Scleredema patients with extensive facial involvement may appear expressionless and may have difficulty in opening their mouths. They may have difficulty with tongue protrusion.

Physical examination should include evaluation of range of motion of the neck, upper extremities, and tongue. Auscultation of the heart and lungs should also be performed.

Note the images below:



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



View Image

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

Complications

Complications include the following:

Laboratory Studies

Laboratory studies can be helpful to identify an associated condition:

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 (A1C) measurements should be obtained in scleredema patients to rule out diabetes mellitus.

Serum protein electrophoresis (SPEP) and immunofixation should be performed in scleredema patients to exclude a monoclonal gammopathy. Both paraproteinemias (also known as monoclonal gammopathies) and multiple myelomas have been reported in patients with scleredema (type 2). The most commonly identified paraprotein is IgG having a kappa light chain; however, an IgA type can occur. Blood dyscrasias usually appear several years after the onset of scleredema. The interval between diagnosis of scleredema and the detection of paraprotein can occur before, concurrently, or after the diagnosis of scleredema. In one report, a delayed paraproteinemia was detected on average up to 10 years following the diagnosis of scleredema.[13] However, other sources quote a median detection of paraproteinemia 2.5 years after diagnosis.

Imaging Studies

No imaging studies are necessary for the diagnosis of scleredema.

Isolated case reports have described scleredema occurring in association with internal malignancies (eg, carcinoma of the gall bladder,[5] malignant insulinoma,[30] carcinoid tumor[6] ). Imaging studies are warranted if this is suggested based on clinical findings.

Some investigators have proposed ultrasonic imaging of skin thickness in scleredema patients as a method to monitor the response to therapy. Computed tomography may demonstrate induration in the involved soft tissues, although it is not often necessary. MRI may highlight the involved areas as well, and some have advocated for MRI usage to determine the extent of disease and monitor progression in select cases.[31]

Other Tests

A punch biopsy or incisional biopsy of lesional skin that extends to include subcutaneous fat is recommended.

Histologic Findings

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, 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) and there is an absence of a fibroblast proliferation (unlike scleromyxedema or nephrogenic systemic fibrosis).

Medical Care

Treatment is unnecessary for postinfectious scleredema as it is typically self-limited. However, in rapidly progressive, fulminant cases, systemic therapy is recommended.[32] Physical therapy, intravenous immunoglobulin, or UVA-1 phototherapy could be considered.

Types 2 and 3 scleredema associated with a monoclonal gammopathy or diabetes typically does not regress spontaneously, and no therapy is consistently effective. Most therapeutic successes described are limited to single case reports or small case series; there are no comparative data and no approved algorithm for scleredema treatment. Expert opinion also differs. In general, it is agreed that treatment of an identified cause is warranted. For type 1 scleredema, antimicrobial agents are used if indicated. For type 2 scleredema, annual screening for a lymphoproliferative disorder, and for those with a monoclonal gammopathy, referral to a hematologist are, indicated. Physical therapy should be considered for all types. However, expert opinion often differs based on personal experience. In a 2017 publication of the European dermatology forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, first-line recommendations were UVA-1 phototherapy or psoralen with UVA (PUVA).[33]

Treatments described in case reports and small case series

A number of therapies, including systemic steroids,[26, 34, 35] cyclosporine,[26, 36] methotrexate,[37] high-dose penicillin,[15, 26] penicillamine, electron beam,[38, 39] and glycemic control with prostaglandin E1 (PGE1)[14] have been reported with mixed success. A report using tamoxifen for its antifibrotic properties noted improvements in two patients.[40] Incidental improvement was noted in one case of scleredema during allopurinol therapy.[41] A 2018 report described three cases of successful treatment with tranilast.[42]

Case reports in the literature describe improvement with UVA-1 phototherapy,[26, 43, 44] narrow-band UVB phototherapy,[45, 46] and PUVA either administered systemically or topically.[26, 47, 48, 49, 50] Case reports also describe these successfully used in combination with colchicine,[51, 52] methotrexate,[53] and physiotherapy.[54] In the authors’ experience, narrow-band UVB phototherapy was not successful.

Physical modalities, such as ultrasonic massage with physical therapy, may improve range of motion and quality of life for some patients alone or in combination with other therapies.[55]

In cases associated with myeloma, chemotherapy directed at the hematologic malignancy has been reported to result in concomitant improvement of the skin disease.[56] For patients with paraproteinemia, extracorporeal photophoresis has been used.[57]

Multiple reports described efficacy with intravenous immunoglobulin therapy in postinfectious, diabetic, and monoclonal gammopathy–associated scleredema that were refractory to more standard therapies.[58, 59, 60]

A 2015 multicenter retrospective review of associations and treatment response among 44 patients was published, finding some response to physiotherapies, systemic steroids, UVA-1, PUVA, and a few combination therapies in a limited number of patients.[26]

Treatment of associated conditions

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.[61]

Treatment of detected blood dyscrasias or diabetes mellitus should be completed.

Consultations

Consultation with a dermatologist to confirm the diagnosis is recommended.

Consultation with a hematologist may be necessary. Refer patients in cases of detected blood dyscrasias and/or monoclonal gammopathies.

Consultation with a physical therapist may be necessary. 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.

Long-Term Monitoring

Patients with longstanding 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.

Medication Summary

There are no comparative data and no approved algorithm for scleredema treatment. Treatments described in case reports and small case series are described in Medical Care.

Author

Lisa K Pappas-Taffer, MD, Assistant Professor of Clinical Dermatology, University of Pennsylvania School of Medicine; Attending Physician, Hospital of the University of Pennsylvania; Staff Physician, Veterans Affairs Medical Center

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 Affairs Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Disclosure: Nothing to disclose.

Lester F Libow, MD, Dermatopathologist, South Texas Dermatopathology Laboratory

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Susan M Swetter, MD, Director, Pigmented Lesion and Melanoma Program, Professor, Department of Dermatology, Stanford University Medical Center and Cancer Institute, Veterans Affairs Palo Alto Health Care System

Disclosure: Nothing to disclose.

Acknowledgements

Misha A Rosenbach, MD Assistant Professor, 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, American Academy of Dermatology, American Medical Academy, Medical Dermatology Society, and Women's Dermatologic Society

Disclosure: Centocor Grant/research funds None

Dina D Strachan, MD Assistant Clinical Professor, Department of Dermatology, St Vincent's Medical Center

Disclosure: Nothing to disclose.

References

  1. Berk MA, Lorincz AL. Scleredema adultorum of Buschke and primary hyperparathyroidism. Int J Dermatol. 1988 Nov. 27(9):647-9. [View Abstract]
  2. Miyagawa S, Dohi K, Tsuruta S, Shirai T. Scleredema of Buschke associated with rheumatoid arthritis and Sjögren's syndrome. Br J Dermatol. 1989 Oct. 121(4):517-20. [View Abstract]
  3. Yachoui R, Traisak P, Jagga S. Scleredema in a Patient with AIDS-Related Lipodystrophy Syndrome. Case Rep Endocrinol. 2013. 2013:943798. [View Abstract]
  4. Matsunaga J, Hara M, Tagami H. Scleredema of Buschke associated with malignant insulinoma. Br J Dermatol. 1992 May. 126(5):527-8. [View Abstract]
  5. Manchanda Y, Das S, Sharma VK, Srivastava DN. Scleredema associated with carcinoma of the gall bladder. Br J Dermatol. 2005 Jun. 152(6):1373-4. [View Abstract]
  6. Yu JI, Park W, Lee KK, Park W. Scleredema adultorum of Buschke associated with a carcinoid tumor. Int J Dermatol. 2009 Jul. 48(7):784-6. [View Abstract]
  7. Venturi M, Damevska K, Ferreli C, Pinna AL, Atzori L, Gocev G, et al. Scleredema of Buschke associated with lichen sclerosus: Three cases. Indian J Dermatol Venereol Leprol. 2018 Oct 4. [View Abstract]
  8. Alp H, Orbak Z, Aktas A. Scleredema adultorum due to streptococcal infection. Pediatr Int. 2003 Feb. 45(1):101-3. [View Abstract]
  9. Cron RQ, Swetter SM. Scleredema revisited. A poststreptococcal complication. Clin Pediatr (Phila). 1994 Oct. 33(10):606-10. [View Abstract]
  10. Malhotra AK, Sethuraman G, Das AK, Sharma VK. Scleredema following scabies infestation. Pediatr Dermatol. 2008 Jan-Feb. 25(1):136-8. [View Abstract]
  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. 1994 Mar. 130(3):394-7. [View Abstract]
  12. McFadden N, Ree K, Soyland E, Larsen TE. Scleredema adultorum associated with a monoclonal gammopathy and generalized hyperpigmentation. Arch Dermatol. 1987 May. 123(5):629-32. [View Abstract]
  13. Rimon D, Lurie M, Storch S, et al. Cardiomyopathy and multiple myeloma. Complications of scleredema adultorum. Arch Intern Med. 1988 Mar. 148(3):551-3. [View Abstract]
  14. Ikeda Y, Suehiro T, Abe T, et al. Severe diabetic scleredema with extension to the extremities and effective treatment using prostaglandin E1. Intern Med. 1998 Oct. 37(10):861-4. [View Abstract]
  15. 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. 1996 Mar. 134(3):597-8. [View Abstract]
  16. 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. 2005 Sep. 44(9):769-70. [View Abstract]
  17. Ranganathan P. Infliximab-induced scleredema in a patient with rheumatoid arthritis. J Clin Rheumatol. 2005 Dec. 11(6):319-22. [View Abstract]
  18. Cole GW, Headley J, Skowsky R. Scleredema diabeticorum: a common and distinct cutaneous manifestation of diabetes mellitus. Diabetes Care. 1983 Mar-Apr. 6(2):189-92. [View Abstract]
  19. Sattar MA, Diab S, Sugathan TN, Sivanandasingham P, Fenech FF. Scleroedema diabeticorum: a minor but often unrecognized complication of diabetes mellitus. Diabet Med. 1988 Jul-Aug. 5(5):465-8. [View Abstract]
  20. Heilbron B, Saxe N. Scleredema in an infant. Arch Dermatol. 1986 Dec. 122(12):1417-9. [View Abstract]
  21. Isaac A, Costa I, Leal I. Scleredema of Buschke in a child with cardiac involvement. Pediatr Dermatol. 2010 May-Jun. 27(3):315-7. [View Abstract]
  22. Nagi A, Memon IA. Scleredema of Buschke in pediatric age group. J Coll Physicians Surg Pak. 2005 May. 15(5):311-2. [View Abstract]
  23. Wright RA, Bernie H. Scleredema adultorum of Buschke with upper esophageal involvement. Am J Gastroenterol. 1982 Jan. 77(1):9-11. [View Abstract]
  24. Sansom JE, Sheehan AL, Kennedy CT, Delaney TJ. A fatal case of scleredema of Buschke. Br J Dermatol. 1994 May. 130(5):669-70. [View Abstract]
  25. Alp H, Orbak Z, Aktas A. Scleredema adultorum due to streptococcal infection. Pediatr Int. 2003 Feb. 45(1):101-3. [View Abstract]
  26. Rongioletti F, Kaiser F, Cinotti E, Metze D, Battistella M, Calzavara-Pinton PG, et al. Scleredema. A multicentre study of characteristics, comorbidities, course and therapy in 44 patients. J Eur Acad Dermatol Venereol. 2015 Dec. 29 (12):2399-404. [View Abstract]
  27. Tran K, Boyd KP, Robinson MR, Whitlow M. Scleredema diabeticorum. Dermatol Online J. 2013 Dec 16. 19(12):20718. [View Abstract]
  28. Farrell AM, Branfoot AC, Moss J, Papadaki L, Woodrow DF, Bunker CB. Scleredema diabeticorum of Buschke confined to the thighs. Br J Dermatol. 1996 Jun. 134(6):1113-5. [View Abstract]
  29. 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. 2005 Feb. 52(2 Suppl 1):41-4. [View Abstract]
  30. 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. 2001 Nov. 40(11):720-1. [View Abstract]
  31. Kurihara Y, Kokuba H, Furue M. Case of diabetic scleredema: diagnostic value of magnetic resonance imaging. J Dermatol. 2011 Jul. 38(7):693-6. [View Abstract]
  32. Sommer LL, Heymann WR. Fulminans in dermatology: a call to action: a recommendation for consideration of the term scleredema fulminans. J Clin Aesthet Dermatol. 2014 Jun. 7(6):42-5. [View Abstract]
  33. Knobler R, Moinzadeh P, Hunzelmann N, et al. European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes. J Eur Acad Dermatol Venereol. 2017 Sep. 31 (9):1401-1424. [View Abstract]
  34. Dogra S, Handa S, Kanwar AJ. Dexamethasone pulse therapy for scleredema. Pediatr Dermatol. 2004 May-Jun. 21 (3):280-1. [View Abstract]
  35. Kurtoğlu S, Yüksel S, Gündüz Z, Per H, Narin N, Kontaş O, et al. Use of high-dose intravenous corticosteroid treatment in a child with scleredema. J Emerg Med. 2004 Feb. 26 (2):245-6. [View Abstract]
  36. Mattheou-Vakali G, Ioannides D, Thomas T, Lazaridou E, Tsogas P, Minas A. Cyclosporine in scleredema. J Am Acad Dermatol. 1996 Dec. 35(6):990-1. [View Abstract]
  37. Seyger MM, van den Hoogen FH, de Mare S, van Haelst U, de Jong EM. A patient with a severe scleroedema diabeticorum, partially responding to low-dose methotrexate. Dermatology. 1999. 198 (2):177-9. [View Abstract]
  38. Tamburin LM, Pena JR, Meredith R, Soong VY. Scleredema of Buschke successfully treated with electron beam therapy. Arch Dermatol. 1998 Apr. 134(4):419-22. [View Abstract]
  39. Lee MW, Choi JH, Sung KJ, Moon KC, Koh JK. Electron beam therapy in patients with scleredema. Acta Derm Venereol. 2000 Jul-Aug. 80 (4):307-8. [View Abstract]
  40. Alsaeedi SH, Lee P. Treatment of scleredema diabeticorum with tamoxifen. J Rheumatol. 2010 Dec. 37(12):2636-7. [View Abstract]
  41. Lee FY, Chiu HY, Chiu HC. Treatment of acquired reactive perforating collagenosis with allopurinol incidentally improves scleredema diabeticorum. J Am Acad Dermatol. 2011 Oct. 65(4):e115-7. [View Abstract]
  42. Sun M, Yang F, Hou M. Successful Treatment of Scleredema Diabeticorum With Tranilast: Three Case Reports. Diabetes Care. 2018 Apr. 41 (4):e40-e41. [View Abstract]
  43. Thumpimukvatana N, Wongpraparut C, Lim HW. Scleredema diabeticorum successfully treated with ultraviolet A1 phototherapy. J Dermatol. 2010 Dec. 37(12):1036-9. [View Abstract]
  44. Kroft EB, Berkhof NJ, van de Kerkhof PC, Gerritsen RM, de Jong EM. Ultraviolet A phototherapy for sclerotic skin diseases: a systematic review. J Am Acad Dermatol. 2008 Dec. 59 (6):1017-30. [View Abstract]
  45. Xiao T, Yang ZH, He CD, Chen HD. Scleredema adultorum treated with narrow-band ultraviolet B phototherapy. J Dermatol. 2007 Apr. 34 (4):270-2. [View Abstract]
  46. Yoshimura J, Asano Y, Takahashi T, Uwajima Y, Kagami S, Honda H, et al. A case of scleredema adultorum successfully treated with narrow-band ultraviolet B phototherapy. Mod Rheumatol. 2016. 26 (2):302-6. [View Abstract]
  47. Grundmann-Kollmann M, Ochsendorf F, Zollner TM, Spieth K, Kaufmann R, Podda M. Cream PUVA therapy for scleredema adultorum. Br J Dermatol. 2000 May. 142(5):1058-9. [View Abstract]
  48. Hager CM, Sobhi HA, Hunzelmann N, et al. Bath-PUVA therapy in three patients with scleredema adultorum. J Am Acad Dermatol. 1998 Feb. 38(2 Pt 1):240-2. [View Abstract]
  49. Martín C, Requena L, Manrique K, Manzarbeitia FD, Rovira A. Scleredema diabeticorum in a patient with type 2 diabetes mellitus. Case Rep Endocrinol. 2011. 2011:560273. [View Abstract]
  50. Nakajima K, Iwagaki M, Ikeda M, Kodama H. Two cases of diabetic scleredema that responded to PUVA therapy. J Dermatol. 2006 Nov. 33 (11):820-2. [View Abstract]
  51. Yüksek J, Sezer E, Köseoglu D, Markoç F, Yildiz H. Scleredema treated with broad-band ultraviolet A phototherapy plus colchicine. Photodermatol Photoimmunol Photomed. 2010 Oct. 26(5):257-60. [View Abstract]
  52. Kokpol C, Rajatanavin N, Rattanakemakorn P. Successful Treatment of Scleredema Diabeticorum by Combining Local PUVA and Colchicine: A Case Report. Case Rep Dermatol. 2012 Sep. 4(3):265-8. [View Abstract]
  53. Shazzad MN, Azad AK, Abdal SJ, Afrose R, Rahman MM, Haq SA. Scleredema Diabeticorum - A Case Report. Mymensingh Med J. 2015 Jul. 24 (3):606-9. [View Abstract]
  54. Martín C, Requena L, Manrique K, Manzarbeitia FD, Rovira A. Scleredema diabeticorum in a patient with type 2 diabetes mellitus. Case Rep Endocrinol. 2011. 2011:560273. [View Abstract]
  55. Bray SM, Varghese S, English JC 3rd. Ultrasonic massage and physical therapy for scleredema: improving activities of daily living. Arch Dermatol. 2010 Apr. 146(4):453-4. [View Abstract]
  56. Rota E, Nallino MG, Bainotti S, Formica M. Nephrogenic systemic fibrosis: an unusual scleroderma-like fibrosing disorder. Rheumatol Int. 2009 Aug 20. [View Abstract]
  57. Stables GI, Taylor PC, Highet AS. Scleredema associated with paraproteinaemia treated by extracorporeal photopheresis. Br J Dermatol. 2000 Apr. 142(4):781-3. [View Abstract]
  58. Aichelburg MC, Loewe R, Schicher N, Sator PG, Karlhofer FM, Stingl G, et al. Successful treatment of poststreptococcal scleredema adultorum Buschke with intravenous immunoglobulins. Arch Dermatol. 2012 Oct. 148(10):1126-8. [View Abstract]
  59. Eastham AB, Femia AN, Velez NF, Smith HP, Vleugels RA. Paraproteinemia-associated scleredema treated successfully with intravenous immunoglobulin. JAMA Dermatol. 2014 Jul 1. 150(7):788-9. [View Abstract]
  60. Barde C, Masouyé I, Saurat JH, Le Gal FA. [Scleroedema adultorum Buschke in a diabetic subject: intravenous immunoglobulin therapy]. Ann Dermatol Venereol. 2009 Apr. 136(4):360-3. [View Abstract]
  61. Rani JD, Patil SG, Murthy ST, Koshy AV, Nagpal D, Gupta S. Juvenile scleredema of Buschke. J Contemp Dent Pract. 2012 Jan 1. 13(1):111-4. [View Abstract]
  62. Eberlein-Konig B, Vogel M, Katzer K, et al. Successful UVA1 phototherapy in a patient with scleredema adultorum. J Eur Acad Dermatol Venereol. 2005 Mar. 19(2):203-4. [View Abstract]

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

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

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

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