We report the case of a female patient with rare combination of limited systemic sclerosis, psoriatic arthritis, and hyperuricemia with X-ray evidence of calcinosis on knees, left elbow and fingertips (right thumb and index finger and left third finger). Therapy with vasodilators and surgical skin incision with drainage was unhelpful. Extracorporeal shock wave lithotripsy and intralesional injections of sodium thiosulphate showed positive results. We found healing of the ulcers, functional improvement, and partial radiographic regression of calcinosis. In addition, visual analog scale pain scores (range 0-10) decreased from 10 to 2.

Systemic sclerosis, Psoriasis, Psoriatic arthritis, Hyperuricemia, Calcinosis cutis, Calcifications, Ulceration treatment

Pavlov-Dolijanovic S, Stupar NV, Zeljkovic S, MIlenkovic R, Perovic M, et al. (2018) Treatment of Dystrophic Skin Calcifications Associated with Limited Systemic Sclerosis and Psoriatic Arthritis by Extracorporeal Shock Wave Lithotripsy and Intra-Lesional Injections of Sodium Thiosulphate: Case Report. J Dermatolog Clin Res 6(3): 1124.

Limited systemic sclerosis (lSSc) is the most common form of systemic sclerosis (SSc), and it was previously identified by the acronym CREST in reference to its most typical clinical manifestations (calcinosis, Raynaud’s phenomenon, esophagitis, sclerodactyly, and teleangiectasias) [1]. In SSc, calcinosis was classified as dystrophic calcification (DC), characterized by normal calcium/phosphorus metabolism [2]. Treatment of calcinosis is difficult since there is a lack of effective treatments [3]. Combination of lSSc, calcinosis and psoriatic arthritis was unusual [4].

Here we report the case of a middle age female patient, with rare combination of lSSc, dystrophic skin calcifications, psoriatic arthritis and hyperuricemia discussing the challenging management of calcified lesion.

We report the case of 63-year-old woman who has been diagnosed with lSSc at the age of 45, on the basis of Raynaud’s phenomenon, sclerodactyly, sclerodermoid face, skin thickening, telangiectasia, anti-centromere antibody positivity, and late nailfold videocapillaroscopy pattern. Our patient worked for 25 years in the petrochemical industry where she was exposed to vinyl chloride monomer. For lSSc, she was treated with vasodilator therapy (amlodipine 5mg/day). At the age of 53 she was diagnosed with DC of knees, left elbow and fingertips (right thumb and index and left third finger). She had fistulas on both knees from which small stones calcifications and white, creamy material was spontaneously draining. She was treated with supportive therapies such as pain medications (acetaminophen and non-steroidal anti-inflammatory agents), treatment of infection, and wound management (cleaning the area over the ulcer with hydrogen peroxide 3%, and antibacterial soap) without effective response in regression of lesions. At the age of 61, she had surgical skin incision with drainage on the tip of her right knee, but this treatment was not sufficient. She had slow wound healing, skin infection and decreased range of motion in the right knee. At the age of 62 she was diagnosed with psoriasis and hyperuricemia. She was treated with febuxostat 40mg once daily. At the age of 63 she was presented to our institution with sclerodactyly, Raynaud’s phenomenon, scars of the fingertips in the index, and middle fingers of the left hand, and telangiectasias on the skin of the face, fingers and mouth. She had subcutaneous nodules on both knees, with white papules of hard consistency on the left knee, and with complicated 5x2 cm ulcerative lesion on the right knee. There was a tumoral mass in the extension region of left elbow whose size was 2x4cm. It was well circumscribed with a firm, hard consistency. She also had plaque psoriasis on the elbows and buttocks, as well as dactylitis of the left fourth toe (Figure 1).

Figure 1 A) plaque psoriasis on the left elbow (black arrow) and tumoral mass 2x4cm in size, well circumscribed with a firm, hard consistency (white arrow); B) bilateral subcutaneous nodules with white papules of hard consistency on the left knee, and complicated ulcerative lesion on the right knee; C) dactylitis of the left fourth toe.

Rodnan skin scor was 7/51. X rays (knee/elbow/hand) showed diffuse subcutaneous calcification (Figure 2).

Figure 2 X-rays of knees (A, B), left elbow (C) and hands (D) showed diffuse subcutaneous calcification.

Laboratory data revealed normal serum phosphorus, calcium and vitamin D levels, elevated erythrocyte sedimentation rate (46 mm/h) and elevated C-reactive protein 11,5 mg/l (reference value < 5 mg/l). Antinuclear antibodies and anti-centromere antibody were positive. Rheumatoid factor was negative. The findings of urinalysis were normal, as well as renal and liver function tests. Dual-energy X-ray absorptiometry scanning showed osteopenia (T-score of total hip was -1.6, and spine -0.2). Diagnosis of psoriatic arthritis was made on the basis of inflammatory low back pain, psoriasis, dactylitis and negative test for rheumatoid factor. She had an unusual combination of lSSc, psoriatic arthritis and DC, and was treated with the immunosuppressive drug (methotrexate 15mg/weekly for psoriatic arthritis and lSSc), folic acid, calcium channel blocker, febuxostat, and vitamin D, pain relief medications (acetaminophen and non-steroidal anti.

inflammatory agents). Patient received 6 extracorporeal shock wave lithotripsy (ESWL) sessions at weekly intervals in both knee regions. After a 6 weeks pause she had another 6 ESWL sessions. After that she received intralesional injections of sodium thiosulphate, 150mg/ml, once a week for 4 weeks. During the follow-up calcifications were spontaneously eliminated, with the remnants of crater-shaped defects. Figure 3 shows small stones that were spontaneously eliminated from the knees.

Figure 3 Small stones that were spontaneously eliminated from the knees.

At the end of treatment period, we found healing of the ulcers (Figure 4),

Figure 4 Patient before treatment (left) and after repeated extracorporeal shock wave lithotripsy sessions and injections of sodium thiosulphate (right).

functional improvement and partial radiographic regression of calcinosis (Figure 5).

Figure 5 Radiographic aspect of the knee [right (A) and left (B)] before and after [right knee (C) and left knee (D)] therapy with extracorporeal shock wave lithotripsy and repeated injections of sodium thiosulphate.

In addition, visual analog scale pain scores (range 0-10) decreased from 10 to 2. Local ethical agreement and informed consent of the patient were obtained.

This case report is showing an unusual combination of limited SSc, psoriatic arthritis, asymptomatic hyperuricemia and dystrophic skin calcinosis. There are only eight reported cases of co-existence of psoriasis and SSc in the English literature [4-9], out of which four had psoriatic arthritis [4,6-8]. Further three cases have been described in Russian literature [10,11]. Hyperuricemia has been generally accepted as a frequent accompaniment of psoriasis and psoriatic arthritis. It has been postulated that the hyperuricaemia results from increased purine synthesis from the rapid epidermal cell turnover. High level of serum uric acid is a risk factor for many diseases like gout, arterial hypertension, coronary heart diseases, etc [12]. Our patient has no gout, but has arterial hypertension. For arterial hypertension, as well as lSSc she received amlodipine. In the Mayo Clinic study, one patient who was treated with amlodipine improved calcinosis [2]. In our patient amlodipine didn’t show positive results for calcinosis treatment.

Recently, Valenzuela et al. confirmed strong association of calcinosis with digital ulcers, and supported a novel association with osteoporosis [13]. This association also suggests that bisphosphonates may have a role in the treatment of calcinosis, but conflicting reports regarding the effect of bisphosphonates on calcinosis have been published [3]. Our patient had osteopenia, and we did not decide to give her bisphosphonates.

Calcinosis in patients with SSc is a late manifestation, most often occurring more than 7.5 years after the diagnosis [2]. In our patient calcinosis developed 10 years after lSSc disease onset.

Literature data show that calcinosis in SSc is associated with digital tip pitting scars [14], late nailfold capillaroscopy pattern [15], as well as anti-centromere antibody [16], which is all recorded in our patient.

 Although the exact pathogenesis of calcinosis in lSSc is unknown, these DC might have appeared due to mechanical stress and tissue hypoxia. Treatment of DC is difficult; there is a lack of effective pharmacological treatments among calcium channel blockers, bisphosphonates, warfarin, minocycline, colchicine, ceftriaxone, probenecid, aluminium hydroxide, intravenous immunoglobulins, biologic agents (infliximab, rituximab), phosphodiesterase 5-inhibitors and prostacyclins [3]. These pharmacological therapies have been successful in isolated cases, small case series, and small open-label studies, but none seems to be consistently effective, and these agents did not receive regulatory approval.

From 2005 to 2016 some case reports of successful treatment with ESWL session and intralesional injections in DC with or without ulcers were published [17-23]. Based on observations of Sultan-Bichat and co workers [18], ESWL efficacy was better against small, ulcerated, and radiopaque DC, and it had an analgesic effect that might make subsequent surgical excision of DC fragments easier. Our patient had ulcerated lesion and we decided to perform ESWL treatment in order to break down the calcifications. By introducing intra-Lesional injections of sodium thiosulphate in DC, our goal was to increase the solubility of calcium. The mechanism of action of sodium thiosulphate involves chelation of calcium into calcium thiosulphate salts, which increases the solubility of calcium up to 100,000 times [24]. We observed partial reduction of the calcifications. Patient also reported less pain and disability in the treated areas when compared with the situation before treatment. No infection or any side-effects were observed.

y side-effects were observed. Baumgartner-Nielsen et al. [19], reported case series of 6 consecutive patients with calcifications due to SSc (5 patients) or nephrogenic systemic fibrosis (one patient) who were treated with intralesional injections of sodium thiosulphate. Clinical response was evaluated at weeks 4 and 12. Size of the lesions was, on average, reduced by 67% by week 4 and by 90% by week 12. Complete remission was obtained in 50% of patients by week 12 and 80% remission was achieved in the remaining 50% by week 12 compared with baseline lesion size before treatment. Furthermore, the patients all reported improvement in pain and disability. The patient with nephrogenic systemic fibrosis died shortly after the third treatment due to complications (acute gastric bleeding) related to gastroscopy. The procedure was evaluated and no suspicions were raised of a link between sodium thiosulphate treatment and the episode that led to death. Most patients reported transient pain related to the injection site. One cutaneous infection in relation to a lesion complicated by ulceration was treated with oral antibiotics. Mentioned authors suggest that intralesional injections with sodium thiosulphate may be considered in severe and /or ulcerated lesions before surgery or if doctor-initiated amputation is planned.

Wolf et al. [20], find therapy with sodium thiosulphate to be novel and promising method for the treatment of DC, which occurs in many connective tissue diseases, including scleroderma, mixed connective tissue disease, dermatomyositis and, rarely, systemic lupus erythematosus.

In conclusion we believe that ESWL followed by injections of sodium thiosulphate presents potentially useful combination of agents in treatment of calcinosis in patients with lSSc.

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