Case 5 -

Calciphylaxis Kim M. Hiatt University of Arkansas for Medical Sciences Little Rock, AR

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Clinical History A 47 year old woman with multiplemyeloma has a hospital course complicated by myocardial infarct, respiratory failure and acute renal failure. She has developed indurated violaceous patches on the posterior legs and back. Case 5 - Figure 1 - This view shows a relatively normal epidermis and dermis with basophilia of the deep dermis Case 5 - Figure 2 - This view of the deep dermis shows abundant calcification of the dermal collagen. This likely represents dystrophic calcification of ischemic collagen Case 5 - Figure 3 - On high power calcification is seen in small vessels of the deep dermis. This is the key to the diagnosis. Histological findings: Ischemic changes in the overlying epidermis (basilar vaculopathy, spongiosis, superficial dermal vasodilatation, erythrocyte extravasation) with or without necrosis Minimal inflammatory infiltrate in the dermis Dermal and subcutaneous medial calcification in small and medium-sized vessels, <600um, average vessel size is 100 um; may require multiple sections to find or may be florid May see intimal hypertrophy and endovascular fibrosis Degree of histologic changes is incongruent with the significant clinical picture Diagnosis: Calciphylaxis Discussion: Calciphylaxis is a relatively rare disorder occurring in the setting of renal insufficiency. Original reports were in patients on hemodialysis, but subsequent cases have not necessarily held that association. Clinically, the lesions present symetrically as violaceous, reticulated or mottled painful patches. These lesions may evolve, with or without overlying bullae, to necrosis and ulceration. Most common sites include the lower extremities, however, trunk, upper extremities, buttocks and genitals have also been reported to be involved. Prognosis is poor, even after surgical and/or medical intervention, with patients typically succumbing to sepsis, often within only a few months. While pathogenesis is poorly understood, one feature remains constant; that is that the patients have end-stage renal disease. Controversial pre-disposing factors include systemic alkylosis after heomdialysis, hypertension, vitamin D therapy, and secondary hyperparathyroidism. Parathyroidectomy has been beneficial for only some patients. The significance of protein C levels is also controversial. Women appear to be at greater risk, as do those patients with poor nutritional status and obesity. There has been considerable discussion on the role of serum calcium, serum phosphate, parathyroid hormone and (calcium x phosphate) levels, but none have shown statistically significant associations. There is also a suggestion that exposure to a sensitizing agent (i.e PTH) followed by a challenging agent (metal salts) may be pathogenic. However, this, too has not been unequivocally substantiated. Differential diagnosis Mönckeberg medial calcific sclerosis – medial calcification of larger arteries, no intimal proliferation and rarely ulcerated. Seen in the setting of diabetics with renal failure. Metastatic calcification – asymmetrical involvement of otherwise normal soft tissues (subcutis, conjunctivae, cornea, joints, blood vesels, viscera) due to an elevated serum (calcium x phosphate) level. Dystrophic calcification – soft tissue calcification in the setting of tissue damage and autoimmune connective tissue disease (CREST, childhood dermatomyositis) Milk-alkali syndrome – subcutaneous calcification, secondary to excessive calcium containing foods and antacids References Alain J, Poulin YP, Cloutier RA, et al. Calciphylaxis: Seven new cases. J Cutan Med Surg. 2000; 4:213-218. Fine A, Zacharias J. Calciphylaxis is usually non-ulcerating: Risk factors, outcome and therapy. Kidney Int. 2002; 61:2210-2217. Galimberti RL, Farias Edos R, Parra IH, et al. Cutaneous necrosis by calcific uremic arteriolopathy. Int J Dermatol. 2005; 44:101-106. Oh DH, Eulau D, Tokugawa DA, et al. Five cases of calciphylaxis and a review of the literature. J Am Acad Dermatol. 1999; 40:979-987. Wilmer WA, Magro CM. Calciphylaxis: Emerging concepts in prevention, diagnosis, and treatment. Semin Dial. 2002; 15:172-186.