ANCA‐associated Vasculitis Found to Cause Nerve Damage in SSc Patient

An elderly woman with scleroderma limited to her skin also developed the autoimmune disorder ANCA‐associated vasculitis (AAV), which led to nerve damage in her lower limbs, a case study described. 

The researchers recommended that patients with scleroderma who experience tingling and numbness in the extremities should be examined for AAV-associated nerve damage. 

The case study, “ANCA‐associated neuropathy in systemic sclerosis: A case report and review of literature,” was published in the Journal of Cutaneous Immunology and Allergy.

Scleroderma, also called systemic sclerosis or SSc, is an autoimmune condition in which the immune system attacks healthy tissues, causing the overproduction of collagen and the buildup of scar tissue (fibrosis) in the skin and other organs. 

According to the investigators, up to 12% of people with SSc also test positive for anti‐neutrophil cytoplasmic antibodies, or ANCAs, which target proteins within white blood cells called neutrophils and monocytes. 

ANCAs are directly implicated in the development of AAV, another autoimmune disease. Known fully as ANCA‐associated vasculitis, it is characterized by damage and swelling — known as vasculitis — in small blood vessels.

However, studies show that very few people with SSc who carry ANCAs go on to develop vasculitis. Moreover, most published reports of SSc and AAV described vasculitis affecting the kidneys or microscopic polyangiitis (MPA), when blood vessel swelling affects multiple tissues and organs, including the kidneys, lungs, skin, nerves, and joints. 

Now, a team of researchers based at the Nagoya University Graduate School of Medicine, in Japan, described the rare case of a Japanese woman with SSc complicated with ANCA‐associated neuropathy. Notably, neuropathy is damage to or malfunction of the nerves that results in numbness, tingling, muscle weakness, and pain. 

At a hospital visit, the 70‐year‐old woman reported having had Raynaud’s phenomenon for 10 years. That SSc-related condition is characterized by decreased blood flow to the fingers and toes in response to cold temperatures or stress. The lessened blood flow leaves fingers and toes feeling numb, prickly, and frigid. The woman also was treated at the hospital for ulcers on her fingers and skin sclerosis on her forearms.

Blood tests revealed the presence of anti-nuclear antibodies (ANA) and anti‐Scl‐70 antibodies, both hallmarks of scleroderma. As a result, she was diagnosed with SSc.

At age 73, the woman developed a persistent cough, with CT scans showing changes to the tissue around the lungs’ air sacs, the alveoli, in line with interstitial lung disease (ILD).

She was admitted to the hospital to investigate paresthesia — abnormal skin sensations including tingling, chilling, burning, and numbness — in both lower limbs.

Tests showed decreased temperature, pain, and vibration sensitivity in the lower limbs, along with mild muscle weakness in the same area. Reduced electrical conduction in the nerves that serve the lower legs also was discovered. 

Nerve biopsies of the lower right leg showed a reduction of nerve fibers that are myelinated, or have the fatty coating that surrounds nerve fibers and enhances electrical transmission. Those biopsies also suggested vasculitis. Additional blood tests were positive for ANCAs that target myeloperoxidase, a protein found within neutrophils. 

The patient was diagnosed with ANCA‐associated vasculitis and treated with the anti-inflammatory medication methylprednisolone, given intravenously (into the vein) for three days, followed by high-doses of oral prednisolone. 

During treatment, further examination did not find scleroderma affecting her kidneys, and her abnormal skin sensations in the limbs gradually lessened.  

A literature search found, in all reported cases, that “SSc diagnosis preceded the ANCA‐associated neuropathy diagnosis,” the team wrote. Additionally, anti‐Scl‐70 antibodies found in SSc patients are frequently associated with the development of AAV, and with limited cutaneous SSc (lSSc) and ILD. 

“In conclusion, if an SSc patient shows symmetric paresthesia of the extremities, it is important for the clinician to consider the possibility of ANCA‐associated neuropathy, especially in an lSSc patient with ILD,” the researchers wrote.