Current Issue
Spring/Summer 2025, Vol. 32 No. 1
Hong Kong J. Dermatol. Venereol. (2025) 32, 66-70
Case Report
Extensive calciphylaxis supported by alarming simple imaging in a renal patient
令人震驚的簡單放射成像確立一名腎病患者的廣泛性鈣化防禦症
Abstract
Calciphylaxis, also known as calcific uraemic arteriolopathy, is a rare cutaneous manifestation of systemic disease occurring in patients with chronic kidney disease. It typically presents as a painful necrotic and progressive skin ulcer of reticular pattern, mostly in the lower legs. It is a condition of substantial morbidity and mortality, with death most frequently due to sepsis. Although skin biopsy is a standard method to confirm the clinical diagnosis, non-invasive imaging often provides valuable clues. We report a case of extensive calciphylaxis in a lady with end-stage renal failure, where clinical radiography showed a typical net-like calcifications.
鈣化防禦症，也被稱為「鈣性尿毒症性小動脈病」，是一種發生於慢性腎臟病患者系統疾病的罕見皮膚表現。它通常表現為疼痛性的皮膚壞死和網狀的漸進性皮膚潰瘍，主要發生在小腿。這是一種發病率和死亡率都很高的疾病，最常見的死因是敗血症。儘管皮膚活檢是確認臨床上懷疑鈣化防禦症的標準方法，但非侵入性的影像亦可以提供有價值的診斷線索。我們報告了一位患有末期腎衰竭的女士的廣泛鈣化防禦症的病例，放射線成像顯示典型的網狀鈣化。
Keywords: Calcific uraemic arteriolopathy, Calciphylaxis, Net-like calcifications
關鍵詞: 鈣性尿毒症性小動脈病、鈣化防禦症、網狀鈣化
Introduction
Calciphylaxis or calcific uraemic arteriolopathy is a rare but devastating cutaneous vasculopathic disorder. It occurs most frequently in patients at the late stage of chronic kidney disease. However it can also occur in people with normal renal function.1 The estimated annual incidence of calciphylaxis in dialysis population is reported to be 1/10,000 to 35/10,000 worldwide.2 The classical clinical picture is that of initial painful skin induration, plaques, nodules, livedo, or retiform purpura, typically involving areas of cutaneous and subcutaneous adiposity, which rapidly progress to stellate necrotic ulcers with black eschars.3 Skin biopsy remains the gold standard for diagnosis, however its role in practice is debated given the risk of provoking new lesions, ulceration, bleeding and infection. Therefore, alternative non-invasive imaging has been suggested to provide clues for diagnosis.
We describe the case of 55-year-old lady with end-stage renal failure requiring peritoneal dialysis. She developed extensive calciphylaxis over both upper and lower limbs. Plain soft-tissue radiographs of affected limbs showed extensive vascular calcifications and a typical subcutaneous net-like calcifications.
Case report
A 55-year-old lady was admitted for painful cutaneous plaques which became ulcerated within weeks. They were found over bilateral lower limbs and fingers. She was on peritoneal dialysis for four years due to end-stage renal failure from IgA nephropathy. She also suffered from diabetes mellitus, hypertension, hyperlipidaemia, atrial fibrillation and ischaemic heart disease. Her usual medications included aspirin, atorvastatin, bisoprolol, diltiazem, methyldopa telmisartan, terazosin, glipizide, pioglitazone, linagliptin, pantoprazole, potassium chloride and sevelamer.
On clinical examination, large necrotic black ulcers were noted over bilateral lower limbs. An area of reticular erythema was present over the right inner thigh. There were also multiple purpuric lesions and necrotic plaques over the fingers, and the right middle finger tip showed gangrenous changes. The lesions were painful and extremely tender on palpation, all peripheral pulses were present (Figure 1).
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| Figure 1 Bilateral lower limbs with large black necrotic ulcers and an area of reticular erythema over the right inner thigh. Fingers with multiple purpuric lesions and necrotic plaques and the right middle finger showing distal dry gangrenous changes. |
Laboratory investigation showed low haemoglobin (11.4 g/dL), elevated white blood cell (22.4X109/L), elevated creatinine (602 umol/L) and an unremarkable liver function test. The albumin-adjusted calcium was high (2.67 mmol/L), the phosphate level was high (1.58 mmol/l) and the plasma parathyroid hormone was also elevated (64 pml/L). Both C-reactive protein (CRP) and Erythrocyte Sedimentation Rate (ESR) were elevated up to 63.1 mg/L and 71 mm/hr. Autoimmune markers including antineutrophil cytoplasmic antibodies (ANCA), anti-nuclear antigen (ANA), anti-extractable nuclear antigen (anti-ENA), and rheumatoid factors were all negative. Coagulation profile including international normalisation ratio (INR), prothrombin time, activated partial thromboplastin clotting time (APTT), protein C, protein S, anti-thrombin III were normal and lupus anticoagulant was negative. The lipid profile was also unremarkable.
Plain X-rays of the affected lower limbs showed curvilinear calcification of vessels of various sizes and also clusters of fine, reticular, netlike pattern of calcification in the soft tissue of bilateral calves (Figure 2). Contrast computed tomography (CT) of the lower limbs showed extensive vascular calcifications and soft tissue calcification. Skin biopsy was declined by the patient due to fear of pain and complications.
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| Figure 2 X-ray films of the bilateral lower limbs showed calcification of large, medium, small arteries and arterioles and a netlike pattern of calcification (arrow) within the soft tissue of calves. |
The diagnosis of calciphylaxis was established based on the high clinical suspicion and compatible X-ray and CT findings. Calcitriol was stopped and intravenous sodium thiosulphate was given. Surgical management including amputation was refused by the patient and she was given supportive care for wound pain and wound care. Finally, the patient succumbed from sepsis two months after the diagnosis of calciphylaxis.
Discussion
Calciphylaxis is characterised by arteriolar calcium deposition. This results in arteriolar thrombosis, leading to ischemia and possible necrosis of the skin and subcutaneous tissues.2 Although the exact pathogenesis is unknown, it is observed that abnormal calcium and phosphorous metabolism, inflammation and hypercoagulability resulted in the vascular and extravascular calcification.4 Risk factors of calciphylaxis include diabetes mellitus, higher body mass index, hypercalcemia, hyperphosphatemia, hyperparathyroidism and the use of nutritional vitamin D, cinacalcet, and warfarin.5 Subcutaneous injections, recurrent hypotension and rapid weight loss in patients with underlying risk factors may induce calciphylaxis. However, obvious trigger cannot be identified in most cases.2
Calciphylaxis has a poor prognosis, with one year mortality rate greater than 50%. Thus a prompt diagnosis and early treatment are crucial.6 Diagnosis often depends on the correlation of clinical and pathologic findings, and a deep incisional biopsy is usually necessary. Nonetheless, such biopsies carry the risk of pain, delayed wound healing, exacerbation of disease and increased chance of wound infection.7 Also, skin biopsies may fail to identify pannicular arteriolar calcification, the main lesion of calciphylaxis especially when the incision is not deep enough to capture the subcutaneous fat layer. Surgical biopsy is considered to be risky or even contraindicated when the process taking place over the penis.8 Radiologic methods becomes popular in the latest medical literature, since it could visualise the hallmark vessel wall calcifications in an non-invasive way.
Plain radiography has numerous advantages. They are readily available, portable, cost-effective, and is capable of detecting small calcifications. In a multicentre retrospective study of 29 patients with calciphylaxis, the authors concluded that the presence of vascular calcification on plain radiography was highly sensitive. A net-like pattern of calcification has a specificity of nearly 90% for calciphylaxis. Moreover, this feature may help to identify patients at risk of future calciphylaxis.9
In a retrospective case series of ten cases of biopsy-proven calciphylaxis, nine cases were found to have radiological evidence of soft tissue vascular calcification. Based on these findings, the authors suggested that findings of superficial vascular calcifications on imaging studies are sensitive for the diagnosis of calciphylaxis. They also recommended CT without contrast for the proximal lower extremity, plain radiography for the distal lower extremity, and mammography for suspected breast calciphylaxis.10
Another retrospective case series comparing vascular calcification between skin biopsy and radiology images found that plain radiographs, CT and mammogram confirmed the presence of arteriolar calcification with resolution of as little as 0.1 to 0.3 mm diameter, nearly equal to that of histopathology. Similarly, the authors concluded that mammography was particularly useful in visualising calcification where the involved tissue site was thick, while plain films and CT imaging are useful in thinner parts of the body such as lower limbs.11
A positive bone scintigraphy, based on increased heterogeneous radiotracer uptake within soft tissues throughout the body with a predilection for areas corresponding to clinical findings, has also been suggested as a highly sensitive and specific tool in the diagnosis of calciphylaxis. Furthermore, bone scintigraphy was found to play a role in monitoring of treatment response to sodium thiosulfate. A diffusely decreased skin uptake indicates treatment completion.12
Our patient displayed classical finding of net-like calcifications in the plain radiographs over the affected limbs, and CT also showed vascular and soft tissue calcifications. With these findings, we are able to confidently confirm the diagnosis of calciphylaxis and initiate treatment accordingly. Soft tissue radiography is readily available, relatively cheap and with minimum side effects. CT gave the advantage of determining the precise location and extent of disease; however, it is limited by availability, non-portability and high radiation exposure. We therefore support the use of non-invasive imaging in expediting the diagnostic process for a lethal disease, especially when a tissue biopsy is not a feasible option.
References
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