Diverse clinical manifestations in patients with granulomatosis with polyangiitis can delay diagnosis and treatment, leading to high mortality rates, a study reports.
These findings highlight the importance of early diagnosis for improving survival. The study, “Granulomatosis with polyangiitis: clinical course and outcome of 60 patients from a single center in South India,” was published in the journal Clinical and Experimental Medicine.
Granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis, is a form of vasculitis that primarily affects the respiratory tract and kidneys.
In about 90 percent of patients, GPA is caused by anti-neutrophil cytoplasmic autoantibodies (ANCA) targeting the proteinase 3 (PR3) protein.
Researchers at St. John’s National Academy of Health Sciences in India set out to describe the spectrum of clinical manifestations, treatments, and outcomes in GPA patients from southern Karnataka, India.
A total of 60 patients diagnosed with GPA and admitted between 2002 and 2012 at St. John’s Medical College Hospital were analyzed. Of those patients, 51 were followed up for a mean period of 56 months. Men represented 35 of the patients versus 25 women.
Researchers assessed disease activity using the Birmingham Vasculitis Activity Score v.3 (BVAS), and damage by the Vasculitis Damage Index (VDI).
Most of the patients — 95 percent — had severe GPA as indicated by the BVAS score.
As expected, most patients had kidney (70%) and upper and lower respiratory involvement (63%).
A quarter of the patients displayed neurological manifestations. Seven patients had peripheral neuropathy (46%) — damage in peripheral nerves causing tingling and numbness; four had mononeuritis multiplex (27%) — similar to peripheral neuropathy but affecting two or more nerve areas; and three exhibited foot drop (20%), with one patient experiencing a stroke.
Articular, or joint, manifestations were also seen in 27% of patients. Other symptoms, such as skin rashes, oral ulcers, and gangrene, were observed in 32%.
Multi-organ involvement is commonly seen in GPA patients. Only 20 participants had just one organ involved, either the kidneys or the respiratory tract.
All others exhibited symptoms in multiple organs. Seven patients had manifestations in three or more organs.
Forty-four patients had one or more clinical complications. The most common were infections, affecting 68% of patients, followed by blood disorders in 50%. In all patients with infection, one or more bacterial infections were observed.
Rarer complications included seizures and congestive cardiac failure, seen in two patients each, and breast cancer in one patient.
All patients were treated with methylprednisone for three days followed by oral steroids. Most also received cyclophosphamide monthly. Methotrexate, azathioprine, and mycophenolate mofetil were used for remission maintenance.
Of the 51 patients that were followed up, 24 achieved remission. But eight of those 24 experienced relapses.
Untreated GPA typically has a poor prognosis, with up to 90 percent of patients dying within two years, usually of renal failure and sepsis.
The team reported that mortality associated with GPA or its treatment occurred in 11 patients (22 percent). Nine patients died of end-stage renal disease, which was the most common cause of death. Two patients died of diffuse alveolar hemorrhage in the lungs.
A previous study reported a 26 percent mortality due to renal failure in GPA patients in England between 1975 and 1985. Researchers suggest that survival has improved thanks to quicker diagnosis and better supportive care in the last decade.
“Early diagnosis reflects better knowledge base and diagnostic facility availability in this part of our country. To further reduce the mortality and morbidity, the time taken for diagnosing needs to be shortened. Reasons analyzed for this delay are attributed to the variable clinical manifestation masquerading as the other common diseases,” the team wrote.
“The most common misleading diagnosis is tuberculosis,” they said.
Distinguishing GPA from tuberculosis can be challenging due to overlapping manifestations. Lesions can be similar on lung imaging, and autoantibodies used to diagnose GPA can also test positive in tuberculosis.
Researchers recommend that GPA diagnosis be done cautiously, especially in areas with a high burden of tuberculosis. They also emphasize the need for investigating vasculitis in tuberculosis non-responders as well, paying attention to those testing negative for acid-fast bacillus (AFB) and persistent radiologic abnormalities.
“Diverse clinical manifestation delay early diagnosis and treatment of this potentially treatable vasculitis. Focused approach could expedite early diagnosis and can reduce the mortality,” they conclude.