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When An Elderly Patient Presents With Calcifications Within Anterior Leg Ulcers
An 86-year-old male with type 2 diabetes presented to the office for evaluation and management of open ulcerations to his left anterior leg. The patient noted scraping the front of the leg on a bicycle pedal roughly one year prior with progressive enlargement of the original small wound (see first photo above). He also noted a 10- year history of purple discoloration with tight, friable skin and mild edema to the left leg only. Previous care from an outside wound healing center included serial debridement, collagenase SANTYL (Smith and Nephew), compression dressings and other modalities.
The orthopedist providing an additional opinion ordered radiographs, which showed multiple soft tissue calcifications along the anterior tibia and fibula with no evidence of cortical disruption (see second photo above). At this point, the orthopedist deferred further treatment to infectious disease, who attempted a six-week regimen of culture-driven IV antibiotics.
The patient returned to his primary physician who ordered labs including complete blood count (CBC), basic metabolic panel (BMP), serum rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), antinuclear antibody (ANA), and Sjogren’s antibody. Testing only revealed a slightly elevated fasting blood sugar. The primary care physician then referred the patient to the primary author for evaluation. Clinical exam showed multiple granular ulcers on the left anterior leg with loose, small calcific masses (previously documented as “bone chips”) within several ulcers. Dorsalis pedis (DP) and posterior tibial (PT) pulses were palpable. The patient had varicosities, hemosiderosis and indurated skin along the anterior left leg. Protective sensation of the extremity was intact. Following physical examination, we performed two, three-mm punch biopsies; one within an open ulceration and one periwound. Pathology revealed deep dermal sclerosis with osteoma cutis and hemosiderin deposition, no evidence of malignancy.
Key Questions To Consider
1. What is your differential diagnosis?
2. What is the most likely diagnosis for this patient?
3. Patients with which conditions are most likely to have this phenomenon?
4. What are the treatment options?
5. What are some logical next steps for such a case?
Answering The Key Diagnostic Questions
1. Calcinosis cutis, venous stasis ulcer, calciphylaxis, dystrophic calcification secondary to trauma, myositis ossificans, pyoderma gangrenosum and systemic sclerosis/morphea.
2. Calcinosis cutis secondary to lipodermatosclerosis.
3. Patients with chronic venous insufficiency with or without lipodermatosclerosis.
4. Compression therapy is the primary treatment, however, a comprehensive plan should include removal of the soft tissue calcifications to ensure granulation and wound closure. Sodium thiosulfate has shown to be a promising treatment in several case reports and case series due to its calcium-chelating effects.1,2,4-6 The following additional modalities may also help improve clinical outcomes: colchicine; intralesional corticosteroids; intravenous immunoglobulin; oral tetracyclines; and extracorporeal shock wave lithotripsy.2 Practitioners should also be aware of and appropriately address any underlying renal disease.
5. In this case, we discussed the findings with the dermatopathologist and a rheumatologist following biopsy. Per our discussions and review of the previous diagnostic testing, the team felt the patient’s ulcers were unlikely systemic sclerosis or a localized variant called morphea, especially given a unilateral presentation. Calciphylaxis was not an appropriate diagnosis given the patient’s normal kidney function.
The final diagnosis was calcinosis cutis secondary to lipodermatosclerosis, especially given the patient’s history of chronic venous stasis and cutaneous changes. We prescribed oral colchicine 0.6mg daily (for its anti-inflammatory properties) and topical 25% sodium thiosulfate (for its calcium-chelating action1,2,4-6). The patient applied the sodium thiosulfate, mixed with zinc oxide paste in a 1:3 ratio, daily under a dry, sterile dressing. The patient saw drastic improvement in his ulcerations with near resolution of all open areas three months into therapy (see last photo above). Since then, the patient’s primary care physician recommended referral to vascular surgery for possible venous ablation.
What You Should Know About Calcinosis Cutis, Lipodermatosclerosis And Sodium Thiosulfate
Lipodermatosclerosis is a sclerosing panniculitis of the lower extremities secondary to chronic venous insufficiency.8Management of lipodermatosclerosis is focused on treating the underlying venous congestion with compression therapy.8Providers need to also be aware of May-Thurner syndrome, a left lower extremity anatomical aberration causing compression and reduced blood flow of the left common iliac vein by the overlying right common iliac artery, as this may also lead to lipodermatosclerosis if left untreated.9 Venous stasis ulceration may certainly occur concomitantly with lipodermatosclerosis, however calcinosis cutis in open ulcerations is much less common, found in roughly 10 percent of cases.8 Epidermal erythema, severe pain, violaceous mottling and livedo reticularis are all seen in early stage (pre-ulcerative) calciphylaxis and can help differentiate this renal disease entity from chronic venous stasis-induced calcinosis cutis.3
Sodium thiosulfate is an industrial agent, commonly used today as a food preservative; intravenous and topical uses exist for multiple medical conditions including calciphylaxis, calcium cutis ulcerations, cisplatin toxicity and cyanide poisoning.7 As a medicine, sodium thiosulfate has antioxidant and vasodilatory properties secondary to its ability to promote nitric oxide synthesis. It also can inhibit calcification of adipocytes and chelate calcium, allowing for the dissolving of subcutaneous calcium deposits.5-7 Medical literature describes sodium thiosulfate used primarily in intravenous and topical forms, however recent investigations describe its use as an intra-lesional agent, although not favorably.9
We also chose to prescribe colchicine for this patient given its anti-inflammatory effects. Colchicine inhibits neutrophil microtubule assembly, preventing adhesion of neutrophils to vascular endothelium and subsequent diapedesis.10 In addition, colchicine blocks secretion of pro-inflammatory cytokines, including IL-1b.11
Final Notes
Physicians need to be aware of the prevalence of calcinosis cutis in patients with chronic venous stasis and that patients can respond favorably to topical or intravenous sodium thiosulfate use. In the very least, it is wise to treat the underlying venous disease with compression therapy and potentially refer to a vascular specialist if indicated. Physicians should also be aware of other causes of calcinosis cutis including trauma, systemic sclerosis and calciphylaxis; adequate laboratory and clinic work-up will help to identify or rule out the presence of these other underlying conditions.
Dr. Casteel is a Diplomate of the American Board of Podiatric Medicine and a Fellow of the Academy of Physicians in Wound Healing. He is in practice in The Villages, Florida.
Dr. Rizkalla is a second-year resident at East Liverpool City Hospital in East Liverpool, Ohio.
Dr. DiDomenico is the Section Chief of the Department of Podiatry at St. Elizabeth Hospital in Youngstown, Ohio and the Director of Fellowship Training of the Reconstructive Rearfoot and Ankle Surgical Fellowship and Residency Training at East Liverpool City Hospital in East Liverpool, Ohio. Dr. DiDomenico is a Fellow of the American College of Foot and Ankle Surgeons.
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2. Howard RM, Smith GP. Treatment of calcinosis cutis with sodium thiosulfate therapy. J Am Acad Dermatol. 2020;83(5):1518-1520.
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8. Lippmann HI, Goldin RR. Subcutaneous ossification of the legs in chronic venous insufficiency. Radiology. 1960;74:279-88.
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10. Cronstein BN, Molad Y, Reibman J, et al. Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils. J Clin Invest. 1995;96:994– 1002.
11. Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440(7081):237-241.
