When the painful ‘bumps’ are calciphylaxis, what’s next?

EXPERT ANALYSIS FROM THE 2017 AAD SUMMER MEETING

NEW YORK – When patients come to the office with painful “bumps” on the legs or elsewhere, panniculitis should be in the differential. And for some patients, said Alina Bridges, DO, the panniculitis may come with the dire diagnosis of calciphylaxis.

Calciphylaxis is an underrecognized crystal deposition disease that’s associated with panniculitis, said Dr. Bridges, speaking at the American Academy of Dermatology summer meeting. When calcium accumulates in small subcutaneous vessels, an occlusive vasculopathy is created within the dermis.

^{Niels Olson/Wikimedia Commons/CC BY-SA 3.0}

A soft-tissue radiograph of the affected area may also be helpful. Calciphylaxis shows as a fine netlike pattern of calcification, a finding that Dr. Bridges said has 90% specificity for the condition.

However, Dr. Bridges said, patients with panniculitis need a biopsy. “Careful selection of biopsy site and a deep specimen containing abundant fat obtained by incisional or excisional biopsy” is the best approach, allowing the pathologist to see the complete picture. In some cases, she said, a double-punch biopsy could also produce adequate specimens.

In addition to the calcium deposition, other pathologic findings may be lobular fat necrosis, with a pannicular vascular thrombosis. Though extravascular calcification can be seen in the panniculus, it’s not uncommon also to see intravascular calcification, said Dr. Bridges, who is the dermatopathology fellowship program director at the Mayo Clinic, Rochester, Minn.

Dr. Bridges said that the patients with calciphylaxis can present with predominant panniculitis or vasculitis, or a mixed picture; patients can also have bullae, ulcers, or livedo reticularis.

The lesions are extremely painful and become increasingly violaceous, with firm subcutaneous nodules. They are variably necrotic, and become more ulcerated over time.

Calciphylaxis is multifactorial and progressive. The prognosis is very poor for individuals with the condition, Dr. Bridges said. The median survival is 10 months, with 1-year survival rates of 46%, and just 20% of individuals with calciphylaxis surviving 2 years after diagnosis.

Gangrene is a frequent complication, and multisystem organ failure often occurs as well, she said.

Calciphylaxis most commonly occurs in individuals with chronic kidney disease and is seen in 4% of hemodialysis patients. However, it may also occur in individuals without uremia. In associations that are incompletely understood, calciphylaxis has been associated with warfarin therapy, connective tissue disorders, Crohn’s disease, liver disease, diabetes, hematologic malignancies, factor V Leiden deficiency, and protein C and S deficiency.

There’s a need for clinical suspicion of calciphylaxis when individuals with any of these conditions present with painful erythematous nodules, or with a vasculitic picture, she said.

Other, more common crystal deposition diseases can also be associated with panniculitis and can be in the differential, Dr. Bridges said. In patients with gout, sodium urate crystal deposition can occur in subcutaneous tissues.

Cutaneous oxalosis can occur as a primary disorder, when patients have metabolic errors and lack alanine-glyoxylate aminotransferase or D-glycerate dehydrogenase. Oxalosis can also be an acquired syndrome in patients with chronic renal failure who have been on long-term hemodialysis.

Although there is not a clearly effective treatment for calciphylaxis, a multitargeted, multidisciplinary approach is needed to help improve tissue health and patient quality of life. Since the primary mechanism of tissue damage is thrombotic tissue ischemia, strategies are aimed at existing clots and at preventing further clot formation.

To correct the calcium-phosphate balance, several medications have been used, including sodium thiosulfate and cinacalcet. For individuals on hemodialysis, a low-calcium dialysate may be used.

^{Courtesy RegionalDerm.com}

A patient with calciphylaxis is shown.

Tissue perfusion and oxygenation can be improved using tissue plasminogen activator, hyperbaric oxygen therapy, and the avoidance of warfarin if the patient requires anticoagulation.

To address wounds directly, debridement can begin with whirlpool time for patients. Surgical debridement may be required, and maggots can also help clean up wound beds.

Palliative care for patients should always include optimizing pain control and improving quality of life for patients with this serious and often life-limiting condition, Dr. Bridges said.

She reported no relevant conflicts of interest.

koakes@frontlinemedcom.com

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