A Case of Idiopathic Scleredema Adultorum of Buschke Yuri Kim, DO,* Alecia Folkes, DO,** Stanley Skopit, DO, MSE, FAOCD, FAAD***

* Resident, 3rd year, Larkin Community Hospital/NSU-COM, South Miami, FL **Intern, St. John’s Episcopal Hospital, Far Rockaway, NY ***Program Director, Dermatology Residency Program, Larkin Community Hospital/NSU-COM, South Miami, FL

Disclosures: None Correspondence: Alecia Folkes, DO; [email protected]

Abstract Scleredema adultorum of Buschke is a rare, benign disease that results in symmetrical induration and thickening of the due to increased and mucin deposition in the dermis. We report the unique case of a patient with no underlying comorbidities who presented with asymptomatic scleredema. Given that this skin condition is difficult to treat and has no standard treatment, this case brings about an important discussion about diagnostic modalities and appropriate management of scleredema adultorum of Buschke.

Introduction presented to our dermatology clinic for a routine kappa light chains were mildly elevated at 27.09 Scleredema adultorum of Buschke, or scleredema, full-body exam. On examination, his back was (normal range 3.30-19.40); however, his kappa/ is a connective tissue disorder that results in mildly indurated with diffuse, flesh-colored lambda ratio was within normal limits. His recent progressive, symmetrical induration and hardening atrophic scars with a peau d’ orange appearance HgbA1c was 5.7. of the skin, usually of the , neck, shoulders, (Figure 1). The patient stated that in the past, upper trunk, and extremities. Histology reveals he had always been told they were acne scars, Discussion although he did not recall a history of acne. He Scleredema is a rare, benign disease first described thick, dermal collagen bundles separated by mucin. 4 as scleredema adultorum of Buschke in 1752. This Scleredema is associated with recent bacterial said the scars were present for approximately 30 years. He denied any symptoms, including disease mostly involves the skin and is characterized or viral infection, paraproteinemia, and 5 by acute skin induration with mild sclerosis. mellitus. It has a female predominance, with a sensations of tightness, pain and itch, and said 1 Lesions are diffuse and symmetrical and consist of female-to-male ratio of 2:1; however, diabetes- he’d undergone no previous treatments. He denied a history of paraproteinemia, recent streptococcal non-pitting edema with ill-defined thickening of associated scleredema is more common in middle- 4 infections or illness, and diabetes mellitus. the skin. This thickening is secondary to increased aged, obese men, with a female-to-male ratio of 6 1,2 collagen and glycosaminoglycans. At times, there 1:3. Scleredema can occur in people of all ages 3 A punch biopsy was performed, revealing mucin is a peau d’orange appearance to the skin. A more but tends to involve adults in their 50s and 60s. deposition between thickened collagen bundles severe, progressive form of scleredema with rapid consistent with scleredema adultorum of Buschke onset, referred to as scleredema fulminant, is life Case Report 2 A 71-year-old male with a past medical history (Figure 2). A colloidal iron stain was used to threatening and requires urgent intervention. of coronary artery disease, hypertension, highlight the dermal mucin deposition (Figures 3, Skin manifestations usually begin on the neck hyperlipidemia, gastroesophageal reflux disease, 4). A SPEP with immunofixation was performed and showed no monoclonal gammopathy. Free and can spread to the shoulders and upper sleep apnea, chronic back pain, and diverticulosis 1 trunk. The disease can also spread to the face, abdomen, and legs, but the hands and feet are spared.7 Associated symptoms include erythema, pruritus, urticaria, dermatographism, pain, and movement restrictions.3,7 Rarer complications include restrictive lung disease, cardiac dysfunction, dysarthria, dysphagia, poor wound healing, and skin infections.1

The exact pathophysiology of scleredema is unknown; however, it is believed to involve an increased expression of type I collagen-producing fibroblasts in the skin.4 Some studies show that factors like infections, inflammation, glucose levels, drugs, genetic mutations, and toxins can stimulate the fibroblasts to overproduce mucin or collagen in Figure 1. Induration of patient’s back along with Figure 2. Biopsy revealing mucin deposition the skin.5,8 Specific mediators include eicosanoids, diffuse, flesh-colored, atrophic scars with peau d’ between thickened collagen bundles in the growth factors, cytokines, and immunoglobulin orange appearance. reticular dermis (H&E, 4x). paraproteins.5 Another hypothesis involves the inhibition of collagen degradation by excessive, non-enzymatic glycosylation.8 The combination of advanced glycation end products and high glucose levels leads to collagen cross-linking.

Studies have shown there are three types of scleredema. The classic form, or type I, is self- limiting, lasts anywhere from several months to two years, and is associated with febrile disease.1 The most common infection associated with type I is streptococcal infection. Other infections include influenza, measles, mumps, chickenpox, and cytomegalovirus. Type II, which is often more chronic, is associated with hypergammaglobulinemia Figure 3 Figure 4 and progression to .7 Type II may also be associated with other malignancies, such as Figures 3, 4. Colloidal iron stain highlighting dermal mucin deposition between thickened collagen bundles (4x, 20x). insulinoma and carcinoma of the gallbladder.6 It

A CASE OF IDIOPATHIC SCLEREDEMA ADULTORUM OF BUSCHKE has an insidious onset without preceding febrile of 2.5 years to 6.9 years between initial diagnosis 2 11 References illness. Type III scleredema, also known as of scleredema and detection of paraprotein. 1. Kalfa M, Koçanaoğulları H, Zihni FY, scleredema diabeticorum, is associated with type I Immunoelectrophoresis studies can be done at Karabulut G, Emmungil H, Inal V. or type II diabetes mellitus. There is a higher risk regular intervals, and it is recommended that Resistant Idiopathic Scleredema: An Underlying of scleredema in patients with poorly controlled patients follow up indefinitely in order to detect 1,6 Not Always Present. Eur J Rheumatol. insulin-dependent type II diabetes, dyslipidemia, possible monoclonal hypergammaglobulinemia, 2015;2(4):163. and thyroid disorders (especially hypothyroidism).3 which can help diagnose type II scleredema. More Underlying diseases rarely associated with research and trials need to be done in order to 2. Sommer LL, Heymann WR. Fulminans scleredema include hyperparathyroidism, formulate a universally accepted treatment for in Dermatology: A Call to Action. A connective tissue disease, carcinoid syndrome, patients affected by scleredema. Our patient refused Recommendation for Consideration of the Term pituitary-adrenocortical neoplasms, and human any form of treatment. However, we are continuing 2,5 Scleredema Fulminans. J Clin Aesthet Dermatol. immunodeficiency virus infection. to follow up with him to monitor for monoclonal 2014;7(6):42-5. gammopathy. We have discussed his results with Diagnosis of scleredema is based primarily on his primary care , who is also closely 3. Rongioletti F, Kaiser F, Cinotti E, Metze D, clinical presentation, but a punch biopsy is needed to monitoring him for diabetes. The patient continues Battistella M, Calzavara-Pinton PG, Damevska make a definitive diagnosis. It will show a normal or to deny any symptoms. 7 K, Girolomoni G, Andre J, Perrot J-L, Kempf slightly thinned epidermis. The dermis will contain W, Cavelier-Balloy B. Scleredema. A Multicentre a decreased number of elastic fibers and thick Study of Characteristics, Comorbidities, collagen bundles separated by mucopolysaccharide Course and Therapy in 44 Patients. JEADV. deposits. Fibroblasts will be normal in number and 2015;29:2399-2404. morphology.5 In some cases, the superficial dermis will have a mild, perivascular, chronic inflammatory 7 4. Kurihara Y, Kokuba H, Furue M. Case of infiltrate with an increased number of mast cells. Diabetic Scleredema: Diagnostic Value of Magnetic Adipose tissue may be replaced with collagen Resonance Imaging. J Dermatol. 2011;38:693-6. bundles in the subcutaneous layer.1 Thickened collagen surrounds the adnexa but shows no 5. Weenig RH, Pittelkow MR. Scleredema and compression or destruction, distinguishing it from Scleromyxedema. Fitzpatrick’s Dermatology in 7 . Special staining such as hematoxylin- General . 8th ed. New York: McGraw- eosin, colloidal iron, and Alcian blue can be used to Hill. 2012. p. 1957-1959. visualize these features under magnification.4 6. Aouthmany M, AE Flischel, SE Helms, RT Treatment is not necessary for type I scleredema, Brodell. Chapter 216: Scleredema. In: Lebwohl which is self-limiting and tends to resolve within MG, Heymann WR, Berth-Jones J, Coulson I, eds. two years. For types II and III, treatment is needed Treatment of Skin Disease. 4th ed. China: Saunders to prevent worsening of symptoms or systemic Elsevier. 2013. p. 700-702. involvement. Scleredema is a difficult disease to treat, with no universally accepted treatments. 7. Fernandez-Flores A, Gatica-Torres M, Ruelas- Treating the underlying disease with strict glucose Villavicencio AL, Saeb-Lima M. Morphological control in scleredema diabeticorum is vital. Much Clues in the Diagnosis of Sclerodermiform research has been done on the effectiveness of Dermatitis. Am J Dermatopathol. 2014; 36 (6): different treatments. Out of all the treatment trials, 449-61. UVA-1 and psoralen plus ultraviolet A (PUVA) light phototherapy had the most successful results. 8. Fang-Yu L, Hsien-Yi C, Hsien-Ching C. It is believed that phototherapy is effective due Treatment of Acquired Reactive Perforating to the upregulation of collagenase by fibroblasts Collagenosis with Allopurinol Incidentally that results in degradation of type I and type III Improves Scleredema Diabeticorum. J Am Acad collagen fibers as well as collagen mRNA.4,9 The Dermatol. 2011;65(4):e115-e117. addition of colchicine to PUVA can be beneficial in that colchicine can suppress TGF-beta-induced 9. Kokpol C, Rajatanavin N, Rattanakemakorn P. upregulation of type I collagen mRNA in human Successful Treatment of Scleredema Diabeticorum dermal fibroblasts.9 can prevent by Combining Local PUVA and Colchicine: A the limitations in range of motion or respiratory Case Report. Case Rep Dermatol. 2012;4:265-8. issues experienced by some patients.3 Allopurinol has been shown to have antioxidant effects that help 10. Gandolfi A, Pontara A, Di Terlizza G, Rizzo in the degradation of thick collagen bundles; it has N, Nicoletti R, Scavini M, Galimberti G, Bosi E. also been shown to reduce vascular oxidative stress.8 Improvement in Clinical Symptoms of Scleredema In one case, frequency-modulated electromagnetic Diabeticorum by Frequency-Modulated neural stimulation (FREMS) was shown to Electromagnetic Neural Stimulation: A Case enhance the microvascular blood flow and smooth Report. Diabetes Care. 2014;37:e233-e234. muscle vasomotor activity in the treatment of scleredema diabeticorum.10 Some trials have shown 11. Dziadzio M, Anastassiades CP, Hawkins success with systemic , cyclosporine, PN, Potter M, Gabrielli A, Brough GM et al. localized electron beam therapy, IVIG, and high- From Scleredema to AL Amyloidosis: Disease dose penicillin.2,3 However, these should be reserved Progression or Coincidence? Review of Literature. for patients with relatively persistent, debilitating Clin Rheumatol. 2005;25:3-15. disease that fails phototherapy or for patients with multiple myeloma.3 Conclusion Our case is unique not only because the patient was asymptomatic, but also because he had no underlying illnesses associated with his scleredema. Therefore, we are unable to classify it as type I, II, or III. However, studies show that abnormal protein levels may be delayed, with a median period

KIM, FOLKES, SKOPIT