If the shoe fits a presumptive clinical diagnosis of calciphylaxis, wear it – and don’t assume that ordering imaging studies or histology will make for a better fit or is even necessary.
That was the key message of Karl M. Saardi, MD, during his video presentation at a virtual meeting held by the George Washington University department of dermatology. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.
“said Dr. Saardi, a dermatology resident at Georgetown University in Washington, D.C.
He presented a single-center, retrospective study that underscored the diagnostic challenges posed by calciphylaxis, a condition for which there are no generally accepted clinical, radiographic, or histologic diagnostic criteria.
The rare skin condition is characterized by calcium deposition in small arterioles and capillaries in the skin and subcutaneous tissue. It’s most common in patients with end-stage renal disease who are on dialysis; however, there is also an increasingly recognized nonuremic variant that’s associated with the use of warfarin, chronic steroids, obesity, and possibly with being antiphospholipid antibody positive.
Calciphylaxis is an extremely painful condition – the pain is ischemic in nature – and it’s associated with substantial morbidity as well as a mortality rate that in many series exceeds 50%. Affected individuals typically present with progressive, painful retiform purpura on the legs, belly, buttocks, and other fatty body sites.
Dr. Saardi’s study entailed a retrospective look at the medical records and pathologic reports of 57 patients who underwent skin biopsy for suspected calciphylaxis. Of the 57, 18 had no antecedent imaging studies done during the preceding 3 months; 8 of those 18 (40%), had a confirmatory positive biopsy. A total of 39 patients did have imaging studies, deemed positive for calciphylaxis in 11 cases, which in only 5 of the 11 imaging-positive cases (45%) were subsequently confirmed by positive biopsy.
And finally, of the 28 patients with negative imaging studies, 10 (36%), had a positive biopsy. Those positive biopsy rates, ranging from 36% to 45%, did not differ statistically. Thus, whether an imaging study was positive or negative, or wasn’t even done, made no difference in terms of the ultimate diagnosis.
“You may not need imaging studies, because imaging has often been done before the consultation is requested because people are looking for things like arterial thrombus, cellulitis, [deep vein thrombosis] or something like that,” Dr. Saardi noted. “In our series, the indication was never calciphylaxis, it was always something like pain, infection, swelling, suspected [deep vein thrombosis], things like that.”
The classic signature of calciphylaxis on plain x-ray is net-like calcifications in skin and subcutaneous tissue. In one study, this often-subtle finding was associated with a 830% increased likelihood of a positive biopsy, with a specificity of 90%; however, these x-ray changes were only found in 13 of 29 patients with biopsy-confirmed calciphylaxis.
“It’s really important when you request plain films in these patients to review the images yourself or together with the radiologist because oftentimes the indication for imaging will be very different from what we’re looking for. Radiologists often won’t know to look for this specifically,” Dr. Saardi said.
The classic histopathologic finding is calcification of the small- and medium-sized vessels in the dermis and subcutaneous soft tissue. However, sometimes all that’s present are small intravascular inflammatory thrombi with intimal hyperplasia.
Skin biopsies are not infrequently falsely negative or nondiagnostic. To maximize the utility of the procedure, it’s important to go deep and gather a tissue sample that extends into subcutaneous tissue.
“You need to do a very deep punch or double-punch biopsy,” he said. “Another key is to avoid biopsy if the pretest probability of calciphylaxis is high because a negative biopsy shouldn’t necessarily reassure you or cause you to withhold treatment. And with the concern about pathergy or Koebnerization of the area causing a wound that’s never going to heal, sometimes a biopsy is not needed if the pretest suspicion is high enough.”
Other investigators have shown that the likelihood of an informative biopsy is enhanced by using a calcium stain on the specimen and having an experienced dermatopathologist do the evaluation. Also, the use of a radiographically guided core needle biopsy to ensure that the physician is getting sufficiently deep into subcutaneous fat is now under evaluation.
In addition to plain radiographs, other imaging methods that are sometimes used to evaluate soft-tissue sites for suspected calciphylaxis included CT and ultrasound. Dr. Saardi is particularly intrigued by reports from investigators at Harvard University regarding the utility of nuclear bone scintigraphy; in one study, this form of imaging was positive in 16 of 18 patients with clinically diagnosed calciphylaxis, versus just 1 of 31 controls with end-stage renal disease.
“We’ve started doing this in situations where biopsy is not desirable or feasible at that moment,” he said.
Dr. Saardi reported having no financial conflicts regarding his presentation.