AAV Patients With Skin Lesions May Be ANCA-Negative, Study Finds
Many ANCA-associated vasculitis (AAV) patients with skin lesions test negative for ANCA antibodies — proteins produced by the immune system that bind to white blood cells called neutrophils, ultimately triggering an autoimmune reaction.
As a result, researchers contend that ANCA testing should not be used as the only criteria to confirm an AAV diagnosis.
“The use of ANCA testing alone to make a diagnosis of AAV is likely to underestimate patients who actually have AAV. Therefore, a thorough full medical evaluation is required to properly evaluate this [group] of patients,” the research team wrote.
The study, “Cutaneous manifestations of ANCA-associated vasculitis: a retrospective review of 211 cases with emphasis on clinicopathologic correlation and ANCA status,” was published in the International Journal of Dermatology.
AAV is an umbrella term for a group of rare autoimmune diseases characterized by blood vessel damage. Depending on where blood vessel damage occurs, the disease can cause several different symptoms.
A skin biopsy is generally performed as a diagnostic test to confirm the presence of blood vessel inflammation. Additionally, although several skin lesions have been associated with AAV, these manifestations are generally not specific.
Patients with palpable purpura — purplish-red spots on the skin — together with leukocytoclastic vasculitis, or small blood vessel inflammation, are often tested for ANCA antibodies as part of an initial diagnostic workup. However, although high levels of ANCA antibodies in the blood are a classical hallmark of AAV, not all patients test positive for them.
To find out if different types of skin lesions may be linked with ANCA positivity or negativity and to characterize the clinical features of ANCA-negative patients, researchers reviewed the medical records of 932 patients with AAV being treated at the Mayo Clinic in Rochester, Minnesota, from March 2010 to March 2020.
Among these patients, 770 had granulomatosis with polyangiitis (GPA), 137 had eosinophilic granulomatosis with polyangiitis (EGPA), and 16 had microscopic polyangiitis (MPA). GPA, EGPA, and MPA are the three main types of AAV. For nine patients, the type of AAV was not specified.
Skin lesions associated with AAV were identified in 211 (23%) patients (110 men and 101 women). Half of the patients with EGPA had skin lesions, while skin problems were present in 17% of those with GPA and in 25% of patients with MPA.
Next, researchers checked for ANCA antibodies and found that 20% of patients with skin symptoms tested negative for the presence of these antibodies. The majority of patients who tested negative for ANCAs had EGPA (75%), followed by those with GPA (15%).
Findings also showed that palpable purpura was the most common type of skin lesion found in ANCA-negative patients (43%). Hives, raised bumps on the skin, nodules (abnormal tissue growths), and skin ulcers (open sores) were less common. Seven (18%) patients had a nonspecific rash.
When analyzing clinical features, researchers noted that the only significant difference between ANCA-negative and ANCA-positive patients was the occurrence of joint and kidney disease, which were more common in ANCA-positive patients.
Microscopic examination of the available tissue samples, known as histopathology, revealed the most common feature was leukocytoclastic vasculitis, followed by extravascular granuloma, or the aggregation of macrophages — a type of white blood cell — on the outside of blood vessels. No differences were identified between the microscopic findings of ANCA-positive and ANCA-negative patients.
“Diagnosis of AAV should not be based on ANCA testing alone since a considerable number of patients with [skin] lesions may be ANCA negative. The clinical or histopathologic findings of skin lesions in this study group did not vary based on ANCA status,” the researchers wrote.
About the Author
