Penile gangrene from calciphylaxis is salvageable with intravenous sodium thiosulfate and early total parathyroidectomy

Penile gangrene is a rare but fatal complication of calciphylaxis in end-stage renal disease (ESRD). To date, there are no guidelines on its management, and outcomes are generally poor with high mortality rate. We present a case of a diabetic patient with ESRD presenting with dry gangrene of the glans penis due to calciphylaxis and successfully treated with intravenous sodium thiosulfate (STS) and early total parathyroidectomy. We further analysed existing literatures on cases that utilized STS in the treatment of penile calciphylaxis.     

Topical cannabis‐based medicines – A novel paradigm and treatment for non‐uremic calciphylaxis leg ulcers: An open label trial

Non‐Uremic Calciphylaxis (NUC) is a rare condition that often manifests as intractable and painful integumentary wounds, afflicting patients with a high burden of co‐morbidity. The Endocannabinoid System (ECS) is a ubiquitous signalling system that is theorised to be dysregulated within wound beds and associated peri‐wound tissues. Preclinical research has shown that the dominant chemical classes derived from the cannabis plant, cannabinoids, terpenes, and flavonoids, interact with the integumentary ECS to promote wound closure and analgesia. This is a prospective open label cohort study involving two elderly Caucasian females with recalcitrant NUC leg ulcers of greater than 6 months duration. Topical Cannabis‐Based Medicines (TCBM) composed of cannabinoids, terpenes, and flavonoids were applied daily to both the wound bed and peri‐wound tissues until complete wound closure was achieved. Wounds were photographed regularly, and the digital images were subjected to planimetric analysis to objectively quantify the degree of granulation and epithelization. Analgesic utilisation, as a surrogate/proxy for pain scores, was also tracked. The cohort had a mean M3 multimorbidity index score of 3.31. Complete wound closure was achieved in a mean of 76.3 days. Additionally, no analgesics were required after a mean of 63 days. The treatments were well tolerated with no adverse reactions. The positive results demonstrated in very challenging wounds such as NUC, among highly complex patients, suggest that TCBM may have an even broader role within integumentary and wound management. This treatment paradigm warrants being trialled in other wound types and classes, and ultimately should be subjected to randomised controlled trials.     

Calciphylaxis in pediatric end-stage renal disease

Calciphylaxis is a rare, but life-threatening complication of end-stage renal disease (ESRD) that has been reported mostly in adult patients. The exact etiology is unknown, but the disease is commonly associated with a high calcium-phosphorus product and elevated levels of parathyroid hormone (PTH). We herein review the published reports on calciphylaxis in ESRD patients less than 18 years old and report the case of a patient with severe calciphylaxis who presented with lower extremity pain, muscle tenderness and difficulty in walking. The serum PTH was low, and the calcium-phosphorus product was normal. The diagnosis of calciphylaxis was confirmed by a muscle biopsy. Treatment with low calcium peritoneal dialysate and substitution of calcium-based phosphorus binders with sevelamer (Renagel) was unsuccessful. The patients clinical condition progressed to extensive soft tissue calcification and ulcerating skin lesions. Nine months after the onset of symptoms, the patient died of cardiopulmonary arrest.     

Calciphylaxis: calcific uremic arteriolopathy and the emerging role of sodium thiosulfate

Calciphylaxis–calcific uremic arteriolopathy, is a serious disorder of arteriolar calcification of the arteriole media and is associated with endovascular fibrosis and thrombosis in subcutaneous adipose tissue. It frequently results in severe ischemia, intense pain, and tissue necrosis with nonhealing skin ulcerations. It usually occurs in chronic kidney disease and especially in patients requiring renal replacement therapy. It is associated with a very high mortality rate, and the number of reports and reviews seemed to have increased over the past 5 years. Advances in therapy and salvaging patients from this high mortality risk have recently been reported with the use of sodium thiosulfate. The new application for this old drug used to treat cyanide poisoning and recently preventing neurotoxic effects resulting in hearing loss in those patients with head and neck cancer receiving cisplatin and carboplatin therapy are discussed. Recently, multiple case reports have demonstrated that sodium thiosulfate therapy has resulted in rapid pain relief, healing of skin ulcerations, and prevention of high mortality risk. This emerging treatment and its success are relatively unknown to many physicians. The purpose of this report is to share with others the emerging role of sodium thiosulfate and its new application as a treatment option to be used in combination with other treatment modalities for calciphylaxis–calcific uremic arteriolopathy. Indeed, as with any new treatment this emerging therapy should be studied in greater detail, but this old drug seems to have a new life in the hands of treating physicians.     

Serine phosphate,threonine phosphate and γ-carboxyglutamic acid in normal and experimentally induced,pathologically calcified rat skin (topical cutaneous calciphylaxis)

Summary The amount of non-collagenous proteins is increased greatly during the pathological calcification of rat skin experimentally induced by dihydrotachysterol (DHT) and Ovalbumin (topical cutaneous calciphylaxis). This is accompanied by an increase in the total amount and concentrations of protein-bound serine phosphate [Ser(P)], threonine phosphate [Thr(P)] and γ-carboxyglutamic acid (Gla), almost all of which can be extracted from the tissue and can be dissociated from collagen in 0.5M EDTA. The EDTA-soluble, non-collagenous proteins are rich in aspartic and glutamic acids, similar to the non-collagenous, EDTA-soluble proteins of bone, cementum and calcified cartilage, and quite distinct from those of dentin and enamel.     

Inhibition of local calcergy by topical application of calciphylactic challengers

Experiments on rats indicate that, with very few exceptions, the calcification which occurs at subcutaneous sites of treatment with lead acetate, cerium chloride, calcium chloride or potassium permanganate is completely blocked or severely inhibited by simultaneous topical application of calciphylactic challengers but not of non-challengers. Despite the few exceptions (which are thought to depend upon specific chemical interactions between some of the compounds tested) this singular correlation between calciphylactic challenging and anticalcergic potency, is highly significant by the Chi-square-test (P<0.001).

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Zusammenfassung Nach subcutaner Injektion von Bleiacetat, Ceriumchlorid, Calciumchlorid oder Kaliumpermanganat tritt an der Injektionsstelle eine starke Verkalkung auf. Bis auf sehr wenige Ausnahmen kann diese durch gleichzeitige lokale Anwendung von calciphylaktischen Provokatoren verhütet oder weitgehend unterdrückt werden. In dieser Beziehung sind nicht provolatorisch wirkende Stoffe inaktiv. Trotz der wenigen Ausnahmen (die wahrscheinlich auf spezifische, chemische Wechselwirkungen zwischen manchen der untersuchten Substanzen beruhen) ist dieser merkwürdige Zusammenhang zwischen calciphylaktisch provozierender und anticalcergischer Aktivität, nach dem ²-Test berechnet, statistisch hochsignifikant (P<0,001).

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Résumé Chez le rat, des expériences ont montré que, sauf de rares exceptions, les calcifications produites au site d'injection d'acétate de plomb, de chlorure de cérium, chlorure de calcium ou de permanganate de potassium sont complètement prévenues ou fortement inhibées par l'application locale simultanée de provocateurs calciphylactiques, mais non par des agents non provocateurs. Malgré quelques exceptions (attribuées à des interrelations chimiques spécifiques entre certaines des substances utilisées), cette curieuse corrélation entre l'efficacité calciphylactique provocatrice et le pouvoir anticalcergique est, d'après le test ², hautement significative (P<0,001).

     

Calciphylaxis der Haut in Folge einer terminalen Niereninsuffizienz Bericht und Diskussion von 3 Fällen

Calciphylaxis is a rare syndrome mostly affecting patients with secondary hyperparathyroidism and in some cases with functional protein C or protein S deficiency. Skin lesions begin as superficial painful patches that progress to deep necrotic lesions. The findings are often misdiagnosed as livedo vasculitis and the prognosis is poor. Histopathologically, calcification in the media of small arteries and arterioles with intimal hyperplasia is seen. It is unclear if this morphologic hallmark is pathogenetic. Therapeutically, the calcium-phosphate product should be lowered pharmacologically by an intensified and modified dialysis treatment and parathyroidectomy.