Calciphylaxis – a challenging & solvable task for plastic surgery? A case report

Calciphylaxis (calcific uremic arteriolopathy) is a rare and poorly understood disease which demonstrates a challenge for different specialities. Media calcifications of arterioles and fat tissue are distinctive and primarily affect the skin but in some cases involvement of nerve sheaths, visceral organs and muscles have been described. Even if diagnosed in an early phase, the chances of success in healing are very low and the mortality is exceptionally high[1].

It is characterized by extremely painful, partly necrotic skin ulcerations, which can be found almost on any part of the body. Hallmark of this disease is a fortified calcification of the arterioles mainly in the subcutaneous tissue and sometimes even calcification of peripheral nerve sheaths and fat cell bodies can be found[1]. The primary clinical picture is multifaceted and can delay diagnosis. The differential diagnosis is challenging and includes vasculitis, cholesterol emboli and diabetic ulcers.

Calciphylaxis can be staged into two phases. Phase one is characterized by pruritus, cutaneous laminar erythemas, which is unspecific and therefore can easily be misinterpreted in the first place. Phase two shows painful ulceration and necrosis[2]. Preferably affected areas are the lower extremities. There are some cases described where also the abdomen and visceral organs were affected. The mortality in phase one is about 30%, but the mortality in phase two is extended up to 80%[3]. These typical ulcerations and necrosis were predominantly presented on the abdomen and both thighs of the patient we treated.

This rare disease was first described by Bryant and White in 1898, where a condition of calcifications and cutaneous necrosis was circumscribed[4]. Selye et al. were the first, who highlightened the pathophysiology of calciphylaxis, labelled the disease in 1962 and characterised it as a systemic hypersensitivity reaction. In animal experiments, Selye et al. could show an induction of calcification of various organs via the combination of sensitizing agents, like Dihydrotachysterol, Vitamin D2,D3 and parathyroid hormone followed by exposure to a challenger, as there are for example metallic salts (iron, aluminium)or trauma[5‐7]. Ketteler et al. referred the condition can lead to an imbalance of two calcification inhibiting proteins; Matrix-Gla and Fetuin A, which are Vitamin K dependant[8]. In animal experiments it could be shown that an essential lack of these proteins can lead to calcification of arteries and even rupturing of the aorta[9, 10].

Even the risk factors seem to be controversial. Predisposing factors are an acute or chronic renal failure, obesity, diabetes, hyperparathyroidism, female Caucasians and an elevated calcium phosphorus product. Further presumably risk factors are phenprocoumon, vitamin K deficiency (phytonadione), lack of fetuin A protein, malignancy, alcoholic liver disease, connective tissue disease, protein C and S deficiency[11]. Interestingly the majority of these patients had normal serum calcium, normal serum phosphorus, normal calcium phosphorus product, normal serum parathyroid hormone levels and normal serum creatinine levels. The mortality rate in this study was 52% with sepsis being the leading cause[12].

Although the risk remains to cause another complicated ulcer, a histological sample excision also including subcutaneous tissue is mandatory. The sample has to be stained with alizarin red or silver-nitrate to differentiate Calciphylaxis from different diseases[11].

Fine et al. suggested bone scintigraphy as one of the first steps to substantiate the diagnosis. In their study, only one of the investigated cases had negative bone scan[13] .The mortality in phase one was 33%. After development of ulcers the mortality reached 80%[13, 14].

In this case report, we highlight a multidisciplinary treatment of a patient, suffering from Calciphylaxis, which after 10 months led to a successful result.

Calciphylaxis still remain a challenge and need further investigation to understand this disease although different causes and numerous therapeutic strategies have been described. A further challenge in the clinical setting is that the therapy for Calciphylaxis is not clearly defined. Independently of the causing agent (factor), the present therapeutic strategy enfolds pain control, surgery, calcium binding agents, phosphorus reducer, cortisone, and antibiotic therapy.

Regarding our patient, we treated him with a combination of surgical approach with intravenous application of binding agents which have led to a successful outcome. However, it should be stated that local flap techniques showed no benefit but merely buried skin grafting was finally crowned with success. Therefore an interdisciplinary approach to this disease via supporting drug therapy and surgical measures may be a promising way to treat patients suffering from Calciphylaxis. The patient was then discharged into rehabilitation centre without further wound problems in his soft tissues and until recently showed no signs of a relapse of Calciphylaxis (Figure3 ).

Notwithstanding, despite the fact that this surgical approach may lead to a satisfactory result in our patient further studies with a larger patient cohort will be needed to determine its efficiency for these patients.