Non-uremic Calciphylaxis and Parathyroid Adenoma, An Uncommon Association Requiring Early Recognition.

Dear Sir,

Calciphylaxis is a multifactorial, highly morbid cutaneous vascular condition. It typically affects patients with hyperparathyroidism due to end-stage renal disease (ESRD). Nonetheless, it has also been reported in the absence of renal compromise.[12] Here, we report an unusual case of non-uremic calciphylaxis (NUC) in which early recognition and prompt diagnosis by a dermatologist would impact its outcome.

A 39-year-old female presented to the emergency room with an 8-week history of irritability, deficient memory, general weakness, and a painful purplish discoloration on her abdomen. She was referred by her primary physician after identifying hypercalcemia (18.6 mg/dl). Physical examination revealed a 6 × 12 cm2 painful, well-defined, violaceous, and indurated plaque on her abdomen [Figure 1a]. She denied any history of thrombotic events, miscarriages, painful ulcers, recent use of anticoagulants, or surgical interventions. Laboratory workup revealed hypercalcemia (17.2 mg/dl), elevated parathyroid hormone (PTH) (2060 pg/ml), vitamin D3 deficiency (<3 ng/ml) with normal renal function, and normal rates in blood count cell and coagulation tests. Diagnosis of primary hyperparathyroidism was established. A thoracic abdominal computed tomography scan revealed a right parathyroid nodule of 3.7 × 2.2 cm2, consistent with a parathyroid adenoma (PA).

Figure 1

Patient lesion at first examination (a) and two weeks later (b)

A skin biopsy on the edge of the abdominal plaque was performed with the presumptive diagnosis of NUC. Histopathology revealed transmural epidermal necrosis, perivascular lymphocytic dermal infiltrate, focal calcifications, and some small, thrombosed blood vessels [Figure 2]. No special stains were required as calcium deposits were clearly evident.

Figure 2

Necrosis and perivascular lymphocytic infiltrate (hematoxylin and eosin stain [H/E], ×4) (a), focal calcifications (H/E, ×40) (b) in the dermis, and some small thrombosed blood vessels (H/E, ×40) (c)

Intravenous hydration, pain management with buprenorphine (0.2 mg/day) and alendronate (70 mg/week) were initiated. Wound care with superoxidized disinfectant solution, dextranomer, petrolatum, and mupirocin ointment every 12 hours was indicated for 3 weeks [Figure 1b]. After this time, an elective parathyroidectomy was performed, and histopathology confirmed the diagnosis of PA. Then, supplementation with oral calcium carbonate (6 g/day for 1 week), vitamin D3 (4000 IU/d), and calcitriol (0.50 mcg/day) was indicated for 2 months. One week after surgery, serum calcium and PTH levels normalized. After 2 months of only using dextranomer, her symptoms greatly improved and skin lesions resolved.

The first case report of calciphylaxis due to primary hyperparathyroidism was described in 1951.[1] Hypercalcemia due to overproduction of PTH results in increased solubility of this mineral with subsequent deposition and occlusion of the microvasculature and infarction of the skin.[3] Clinically, lesions are located on the lower limbs and trunk.[12] Ulceration is associated with a poor prognosis due to the risk of infection and sepsis with a mortality rate of 52%–80%.[4]

Clinicopathological correlation is important for its diagnosis.[3] Histopathological confirmation remains the gold standard for this purpose.[1] Histopathologic findings include arteriolar calcification in subcutaneous fat, endovascular fibrosis, and thrombosis.[1] Differential diagnosis include vasculitis, cholesterol embolism, warfarin-heparin-induced necrosis, antiphospholipid syndrome, and cryoglobulinemia.[15]

Multidisciplinary treatment is required. Main objectives in our case were to prevent septic complications, pain management, and correction of underlying disease with parathyroidectomy. Survival of patients with this clinical scenario has only been reported by a few authors.[2345] According to previous reports, mortality rate is 36.8%, while recovery was observed in 91% of patients who underwent parathyroidectomy.[2345]

There are 15 reported cases of primary hyperparathyroidism due to parathyroid adenomas as a cause of secondary calciphylaxis.[234] These cases exhibit a poor response when parathyroidectomy is not performed.[2345] The lack of controlled studies does not allow to establish prognostic factors for survival.[2] In our case, normalization of PTH levels through surgery was beneficial for the improvement of skin lesions. Our case highlights the role of dermatologists in the early recognition of calciphylaxis secondary to primary hyperparathyroidism. The establishment of timely treatment, appropriate wound care, and prevention of infection positively impact the prognosis of this condition.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.