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Anais Brasileiros de Dermatologia

Print version ISSN 0365-0596

An. Bras. Dermatol. vol.87 no.5 Rio de Janeiro Sept/Oct. 2012

https://doi.org/10.1590/S0365-05962012000500014 

CASE REPORT

 

Calciphylaxis, a diagnostic and therapeutic challenge: report of a successful case*

 

Calcifilaxia, desafio diagnóstico e terapêutico: relato de um caso bem sucedido

 

 

Eduardo Vinicius Mendes RoncadaI; Marilda Aparecida Milanez Morgado de AbreuII; Mayra Falcão PereiraIII; Claúdia Cardoso Macedo de OliveiraIV; Gisele Alborghetti NaiV; Deusita Fernandes Gandia SoaresVI

IAssistant Professor, Dermatology Service of the Regional Hospital of Presidente Prudente, University of the West Paulista Region (Hospital Regional de Presidente Prudente - Universidade do Oeste Paulista (HRPP-UNOESTE) - São Paulo (SP), Brazil
IIMaster degree and PhD in Dermatology - Head of the Dermatology Service of the Regional Hospital of Presidente Prudente, University of the West Paulista Region (Hospital Regional de Presidente Prudente - Universidade do Oeste Paulista (HRPP-UNOESTE) - São Paulo (SP), Brazil
IIIDermatologist - Private practice - São José dos Campos (SP), Brazil
IVDoctor - Specialized in Dermatology at the Universidade do Oeste Paulista (Universidade do Oeste Paulista - UNOESTE) - Dermatology Service of the Regional Hospital of Presidente Prudente, University of the West Paulista Region (Hospital Regional de Presidente Prudente - Universidade do Oeste Paulista (HRPP-UNOESTE) - São Paulo (SP), Brazil
VPhD in Pathology from the State Paulista University (Universidade Estadual Paulista - UNESP) - Professor at the Pathology Department, University of the West Paulista Region (Universidade do Oeste Paulista - UNOESTE) - São Paulo (SP), Brazil
VISpecialized in Dermatology at the School of Medicine of São José do Rio Pardo (Faculdade de Medicina de São José do Rio Preto - FAMERP) - Assistant Professor at the Dermatology Service, Regional Hospital of Presidente Prudente, University of the West Paulista Region (Hospital Regional de Presidente Prudente - Universidade do Oeste Paulista (HRPP-UNOESTE) - São Paulo (SP), Brazil

Mailing address

 

 


ABSTRACT

Calciphylaxis, also known as calcific uremic arteriolopathy, is a severe complication often observed in patients with hyperparathyroidism secondary to chronic renal failure, which occurs mainly in women. It is characterized by ischemic tissue loss secondary to progressive vascular compromise. This is a rare and severe condition and its pathogenesis is unclear. The best treatment is prevention, especially in order to maintain adequate levels of calcium and phosphorus. We describe a case of this disease in a patient with hyperparathyroidism secondary to chronic renal failure who underwent medical treatment, surgical debridement and total skin autografts, with resolution of symptoms after 6 months.

Keywords: Blood vessels; Calcium metabolism disorders; Hyperparathyroidism, secondary; Ischemia; Renal insufficiency, chronic


RESUMO

A Calcifilaxia, também conhecida como arteriolopatia urêmica calcificante, é uma complicação freqüentemente observada nos pacientes com hiperparatireoidismo secundário à insuficiência renal crônica, ocorrendo principalmente em mulheres. Caracteriza-se por necrose isquêmica cutânea, de instalação aguda e progressiva, secundária à calcificação de vasos sanguíneos de pequeno ou de médio calibre. Trata-se de uma afecção rara e grave, cuja patogênese é obscura, e o melhor tratamento é a prevenção, especialmente visando manter os níveis adequados de cálcio e de fósforo. Descrevese um caso desta moléstia em paciente portadora de hiperparatireoidismo secundário à insuficiência renal crônica, submetida a tratamento clínico, desbridamento cirúrgico e enxertos autólogos de pele total, com resolução completa do quadro após 6 meses.

Palavras-chave: Distúrbios do metabolismo do cálcio; Hiperparatireoidismo secundário; Insuficiência renal crônica; Isquemia; Vasos sanguíneos


 

 

INTRODUCTION

Calciphylaxis, also called calcific uremic arteriolopathy (CUA), was first described by Selye in 1962. 1 Its incidence is estimated at 1% a year in up to 4% of dialysis patients, especially women. 2,3

CUA is a panniculitis associated with subcutaneous calcinosis, possibly multifactorial, but whose etiology remains unclear. 4,5 The diagnosis is confirmed by histopathological examination of a skin biopsy. Calcification and obstruction of small or medium size cutaneous blood vessels can occur, with hyperplasia of the tunica intima and tunica media, septal and/or lobular subcutaneous tissue necrosis, resulting in distal ischemia and painful ulcers, which can lead to gangrene and amputation of extremities. 3,6,7

It is seen in patients with chronic renal failure (CRF), mainly the ones who are undergoing dialysis or pre-dialisys. 2,3 The hyperparathyroidism (HPT) secondary to nephropathy is the major cause of CUA, especially when the product calcium (Ca) x phosphorus (P) is above 70 mg2/ dL. 3,8 However, CUA also affects renal transplant patients, seropositive for human immunodeficiency virus (HIV), patients with primary HPT or alcoholic cirrhosis.7,9 Vasculitis, systemic lupus erythematosus, antiphospholipid antibody syndrome and Henoch-Schoenlein purpura are conditions that must be ruled out. 5,7,10

CUA recognition and early treatment prevent skin necrosis and fatal systemic changes.10 However, there is no consensus on the best treatment to be used.8 We report here a successful case of this rare disease.

 

CASE REPORT

A 62-year-old white woman, retired, born and raised in Presidente Prudente, SP, had been complaining of leg ulcers for 4 years. She developed livedoid spots, erythematous-violaceous plaques and painful subcutaneous nodules located on the distal legs. These progressed to necrosis, causing ulcers between 1 and 7 cm, with irregular borders, erythematous-violaceous edges and granulation tissue covering the bottom, with purulent discharge (Figure 1). She had hypertension, heart disease, obesity and CRF. not on dialysis due to diabetes mellitus type II. Laboratory tests revealed elevated canalicular enzymes, albumin and PTH (Table 1). Plain radiographs of the left leg showed irregularity of the soft tissue and vascular calcification in the medial-distal region to the level of the foot (Figure 2). Histopathology showed hyperplastic and perpendicular capillaries in the superficial dermis, extending to the epidermis, mild lymphocytic infiltrate with intermingled melanophages, and also calcification in the vascular wall of the reticular dermis and subcutaneous tissue, most evident by Von Kossa staining (Figures 3, 4). Stains for fungi, acid-fast bacilli and spirochetes as well as culture for bacteria and fungi were negative. Diagnosis: Calciphylaxis.

 

 

 

 

 

 

The patient was treated with hypophosphatemic diet, oral replacement of calcitriol 0.5 mcg/day, analgesia, surgical debridement of necrotic tissues and occlusive dressings with 1% papain and 1% chloramphenicol. After reducing the levels of parathyroid hormone and serum P, two total skin autografts were made, leading to complete healing of ulcers within 6 months (Figure 5). The patient's HPT is controlled and after one year of follow up the skin lesions have not reappeared.

 

 

DISCUSSION

In the past, it was believed that the metabolic changes of Ca, P and PTH were the only factors which caused CUA. 3,4 The increase of P and Cax P was reported. However, a deficit of calcitriol and abnormalities in the Ca and vitamin D receptors, observed in CRF with HPT seem to be the factors which trigger the hyper secretion of PTH. 2,3 In advanced nephropathy, hyperphosphatemia occurs, becoming the major aggravating factor of both HPT and CUA. 7,8

However, cases of CUA in the presence of normal or slightly altered levels of PTH, Ca and P have been reported. 5,10 About 70 % of the patients suffering from CUA have serum P > 5 mg/dL5; serum Ca > 10.5 mg/dL is found in 20%; and 33% of them present product Ca x P > 70 mg2/dL2, showing that there is not only one determinant factor which causes this disease. 5,10 Thus, other conditions contribute to the development of CUA, such as obesity, rapid weight loss, diabetes mellitus, hypoalbuminemia, protein C and/or S deficiency, the use of heparin, insulin or iron, trauma, prolonged systemic corticosteroid therapy, immunosuppression and metabolic alkalosis post hemodyalisis. 9 CUA rarely occurs in patients with normal renal function, in which cases it is important to rule out breast cancer, cholangiocarcinoma, multiple myeloma, severe liver disease and primary HPT. 10

CUA has poor prognosis, with a mortality rate that reaches up to 80%. Septicemia is the main reason for death, mostly in the first 10 months after the diagnosis. 5,9 Complications resulting from ischemia and systemic calcinosis include: acute myocardial infarction, stroke, mesenteric ischemia, peripheral arterial obstructions, dementia and sensitive polyneuropathy.6 The correction levels of Ca, P and PTH are the initial steps of therapy and consequent reduction of morbimortality. 8,9,10

Aiming at the homeostasis of Ca/P metabolism, a hypophosphatemic diet (< 800 mg/day) is adopted, which is obtained by controlled ingestion of proteins;4,8 Ca-free P chelators so as not to increase the Ca/P product; calcium carbonate is contraindicated5. Sevelamer hydrochloride appears to have advantage over other chelating agents because it does not induce hypercalcemia. 5

Wounds that are very painful require analgesia. Non-steroidal anti-inflammatories should be avoided because there is a risk of renal function deterioration4 and corticosteroids are not used since they may trigger CUA. 5,10 Locally, surgical debridement of necrotic areas, occlusive dressing with fibrinolytic agents and antibiotics are other options. 8,9 The use of hyperbaric oxygen therapy may be another option5. Parathyroidectomy is used for refractory cases with serious HPT. 4,5

In this report, unlike most previously described cases, the patient did not have a Ca x P product very high (approximately 50 mg / dL), PTH and serum calcium levels were not so important and pre-dialysis. Other risk factors such as obesity, diabetes and hypoalbuminemia contributed to the development of the AUC. The normal results of laboratory tests such as VDRL, FTA-Abs, ANA and antiphospholipid antibodies, exclude other contemplated diagnoses. The absence of clinical signs of peripheral arterial disease added to normal ultrasound findings (Duplex Scan) of the lower limbs eliminated the possibility of arteriosclerosis with calcification in the arteries.

A Ca x P product above 45, as in our case, is enough to precipitate calcium phosphate in the blood vessels resulting in calcification, obstruction and hyperplasia of intimal and medial layers, and consequently necrosis of subcutaneous tissue and formation of ulcers. 3,10 This justifies resetting the calcitriol which is not synthesized by chronic renal failure patients. Skin grafts are helpful in healing, but they are only valid after the patient reaches metabolic balance. In a literature review on the databases from 1997 to 2010 made by Lilacs and Medline there were rare reports of successful treatment similar to the one described here.

It is important to emphasize that preventive measures reduce the risk of CUA in patients with CRF; furthermore, early diagnosis and treatment of skin lesions are vital for the patient.

 

 

REFERENCES

1. Selye H. Calciphylaxis. Chicago, IL: University of Chicago Press; 1962. p.37-82.         [ Links ]

2. Ivker RA, Woosley J, Briggaman RA. Calciphylaxis in three patients with end stage renal disease. Arch Dermatol. 1995;131:63-8.         [ Links ]

3. Bonamigo RR, Mariante JC, Pisani AC, Bakos L. Calcifilaxia e hiperparatireodismo primário. An Bras Dermatol. 1995;70:358-9.         [ Links ]

4. AI Beladi FI. Catastrophic calciphylaxis in a patient with lupus nephritis and recent onset of end-stage renal disease. Saudi J Kidney Dis Transpl. 2010;21:323-7.         [ Links ]

5. Jorgetti V. Arteriolopatia urêmica calcificante (calcifilaxia). Boletim Científico [Internet]. 2003 Maio [acesso 07 out 2010]. Disponível em: http//portal.samaritano.com.br/pt/interna.asp?page=1&idpagina=309.         [ Links ]

6. Hafner J, Keusch G, Wahl C, Sauter B, Hürlimann A, von Weizsäcker F, et al. Uremic small artery disease with medial calcification and intimal hypertrophy (socalled calciphylaxis): a complication of chronic renal failure and benefit from parathyroidectomy. J Am Acad Dermatol. 1995;33:954-62.         [ Links ]

7. Marron B, Coronel F, López-Bran E, Barrientos A: Calcifilaxia. Una patogenia incierta y un tratamiento controvertido. Nefrología. 2001;21:596-600.         [ Links ]

8. Mendonça DU, Lobão RRS, Carvalho AB. Revisäo: Hiperparatitoidismo secundário-visão atual de aspectos fisiopatológicos e clínicos. J Bras Nefrol. 2002;24:48-55.         [ Links ]

9. Mazhar AR, Johnson RJ, Gillen D, Stivelman JC, Ryan MJ, Davis CL, et al. Risk factors and mortality associated with calciphylaxis in end-stage renal disease. Kidney Int. 2001;60:324-32.         [ Links ]

10. Rogers NM, Teubner DJO, Coates TH. Calcific uremic arteriolopathy: advances in pathogenesis and treatment. Seminars in Dyalisis. 2007;20:150-7         [ Links ]

 

 

Mailing address:
Eduardo Vinicius Mendes Roncada
Rua Padre João Goetz, 748 - Apto 1001 Vila Guaíra
19061-460 Presidente Prudente, SP
E-mail: eduardoroncada.dermatologia@hotmail.com

Received on 22.07.2011.
Approved by the Advisory Board and accepted for publication on 29.09.2011.
Financial Support: None
Conflict of Interests: None

 

 

* Study carried out at the Dermatology Service, Regional Hospital of Presidente Prudente, University of the West Paulista Region (Hospital Regional de Presidente Prudente - Universidade do Oeste Paulista (HRPP-UNOESTE) - São Paulo (SP), Brazil.

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