LAS VEGAS — In a proportion of patients, severe vasculitis is a life-threatening emergency in which hospitalization and high-dose steroids are a priority even before the etiology is understood, according to a specialist who pointed out easily missed signs of major organ involvement.

Rheumatologists are the appropriate audience for a message about how to best recognize emergency cases because they are on the front lines, according to the specialist, Alexandra S. Villa-Forte, MD, MPH, who is affiliated with the Center for Vasculitis Care and Research at the Cleveland Clinic in Cleveland.

Citing a study indicating that 90% of referrals to vasculitis treatment centers come from rheumatologists, Villa-Forte was in the midst of explaining the best diagnostic steps at Perspectives in Rheumatic Diseases (PRD) 2026 when she veered into a warning about the need to recognize emergency cases. These need immediate attention even when the workup is incomplete.

“This is the most important thing I will say today. A diagnosis can be delayed in most patients as information is gathered, but there are patients at imminent risk of rapid progression,” Villa-Forte said. These cases require empiric therapy — often high-dose steroids — and urgent hospitalization with minimal delay.

Speaking at PRD 2026, Villa-Forte illustrated this point with examples, two of which involved relatively young patients presenting with symptoms that did not cause immediate alarm.

Cases Raising Suspicion of Multiorgan Vasculitis

In one case, a 32-year-old patient with a history of chest pain and highly elevated systolic blood pressure proved to be in renal failure on the basis of laboratory testing. Polyneuropathy, microscopic hematuria, a livedoid rash, and a pulmonary infiltrate consistent with alveolar hemorrhage were enough to raise suspicion of multiorgan involvement. Had the patient not been promptly hospitalized, irreversible loss of kidney function was among the potential complications.

“Rheumatologists are used to pattern recognition, and this skill can be very helpful when putting the symptoms of vasculitis together,” Villa-Forte said. She encouraged clinicians to think of vasculitis when struggling with diverse symptoms that do not seem to add up.

In a second example, Villa-Forte described a 42-year-old man who presented with a new skin lesion as well as swelling and pain in multiple joints. Starting 2 weeks prior, nonspecific constitutional symptoms included fever, cough, and fatigue, and these were accompanied by nausea and vomiting.

In the context of this presentation and the rash, which is a common manifestation of vasculitis, a skin biopsy was ordered. Villa-Forte emphasized that all biopsies need to be ordered with direct immunofluorescence (DIF) to detect antibodies and complement.

“In a patient suspected of vasculitis who presents with rash, always biopsy the skin, but you must specify a DIF. This is not routine, so you must ask,” said Villa-Forte, who explained that this test often confirms the diagnosis.

Despite the patient’s young age, renal insufficiency was in an advanced state. In this case, hematuria and proteinuria did not immediately diminish with therapy, causing concern about kidney failure.

In the hospital, pulse intravenous glucocorticoids were soon joined by mycophenolate mofetil at a dose of 500 mg twice daily. But separate steps had to be considered to prevent further renal deterioration. The many complications, including weight gain, hyperglycemia, skin lesions, and arthralgia improved slowly.

The point is that these forms of advanced vasculitis are complicated, involving multiple strategies to control damage to involved organs.

“Patients with severe vasculitis sometimes get to me when it is already too late,” she said, meaning that complications have become irreversible. She called early recognition of rapidly progressing multiorgan disease “critical” before major organs fail, reiterating that serious vasculitis can occur in patients who have not yet developed remarkable symptoms.

“When in doubt, seek specialist input,” Villa-Forte said, adding that there is no harm in a preemptive hospitalization if the clinical picture produces concern.

In regard to treating severe vasculitis as a medical emergency, Peter Merkel, MD, who is both chief of the Division of Rheumatology at the University of Pennsylvania and the director of the Penn Vasculitis Center in Philadelphia, concurred.

“I agree that for patients suspected of having severe vasculitis, urgent evaluation by an expert in the diagnosis and management of vasculitis should be strongly considered,” said Merkel, who has been an author or coauthor on multiple clinical trials of vasculitis treatments and participated in the development of guidelines for specific subtypes, such as those for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.

Vasculitis is narrowly defined as vessel wall inflammation, a condition that can result in ischemia from vessel occlusion or hemorrhage and aneurysm from vessel wall fragility. Inflammation of the adjacent tissue, which can involve such complications as granuloma formation, necrosis, and myositis, can be part of a primary disorder or secondary to an underlying disease.

Clues to Use in Prioritizing Diagnostic Tests

Distinguishing between large-vessel, medium-sized vessel, and small-vessel vasculitis is an important first step for prioritizing diagnostic tests, but Villa-Forte emphasized that no single diagnostic test reliably confirms the diagnosis. Clinical presentations are highly variable, and any organ system can be affected.

The three presentations most closely related to vasculitis are multisystem complaints for which there is no other immediate explanation; signs of chronic inflammation, such as fever, unintentional weight loss, or fatigue; and unexplained ischemia, such as an unusual vessel distribution for atherosclerosis, young age of occurrence, symptoms of limb claudication, cranial symptoms, and dizziness, syncope, and stroke. In each case, focus on vasculitis should increase as other etiologies are ruled out.

Due to the potential for multisystem involvement, Villa-Forte suggested that uncommon symptom patterns should attract attention during the detailed history and physical examination that are fundamental to identifying a disease for which no single diagnostic tool confirms the diagnosis.

In the case of ischemia, for example, dizziness or limb pain might prompt suspicion of a vascular disorder, but when they occur in a young patient or involve sites unusual for underlying atherosclerosis, simple evaluations, such as pulse strength, disparities in blood pressure levels, or vessel bruits, can be useful for considering underlying vasculitis, Villa-Forte said.

Yet, these measures are just a clue to begin considering underlying vasculitis. Similarly, skin rashes of an unexplained cause can signal vasculitis, but they are not helpful without a biopsy read with DIF, Villa-Forte said. She said that there is no typical vasculitis-associated rash by location or presentation.

“The skin rashes and lesions can have any type of appearance. I can tell you this is true, because every time I think I have seen it all, I find I haven’t,” she said.

Moreover, few clinical manifestations of vasculitis, including skin lesions, provide insight into the underlying etiology. As an example, Villa-Forte cited a report of leukocytoclastic vasculitis in a patient with palpable purpura.

“There are more than 50 different diseases that produce leukocytoclastic vasculitis,” she said.

Biopsies of lesions suspected of stemming from vasculitis are generally helpful, but they are not generally practical in internal organs. In addition, blind biopsies in an asymptomatic location have a very low yield, according to Villa-Forte. She also advised against temporal artery biopsies to confirm giant cell arteritis. Again, even in symptomatic patients, these have a low yield.

Locating vasculitis in involved areas of the circulation or adjacent tissue is helpful for judging disease activity and considering underlying etiologies, but this is not the goal.

“Making the diagnosis of vasculitis is not enough. It is not final,” she said. Management and risks differ by the types and location of vasculitis. Focal thrombotic complications are not handled the same way as multisystem disease. Even when the etiology has been isolated, the severity of the condition “is critical for the timing of referral,” she said.

Villa-Forte did not advocate referring every suspected case of vasculitis to a specialist at an expert center. Rather, with the exception of suspected cases of rapidly progressing multiorgan disease, she advised clinicians to complete as much of the workup as possible before referral.

Again, although there is no diagnostic study appropriate to confirm vasculitis in all patients, steps such as biopsy in those who have a skin rash and laboratory tests can rule out many of the mimics, such as hepatitis, HIV, and fungal infections. Elevated inflammatory markers, such as C-reactive protein and erythrocyte sedimentation rate, might be clues to an underlying inflammatory process, even if Villa-Forte cautioned that none of these tests are reliable for ruling disease in or out.

A negative test for antineutrophil cytoplasmic antibodies, for example, can be helpful in context, but many patients with vasculitis are ANCA-negative, so it is never a screening tool, according to Villa-Forte.

Villa-Forte called imaging “a big part of the diagnostic process,” but, again, this does not necessarily make a diagnosis of vasculitis even if it can be helpful for showing solid organ involvement in patients with medium- or large-vessel disease.

Getting a Second Opinion

Despite her assertion that rheumatologists are on the front line for suspecting vasculitis and at least starting the diagnostic process, she acknowledged that it is reasonable to seek a second opinion. Atypical presentations are common, and synthesizing the history, the clinical findings, and the reports from radiology and pathology often produces a complicated picture that an independent expert can help to interpret.

Second opinions can also be helpful when patients do not have the expected response to an appropriate therapy, when adverse events during first-line therapy suggest the need for alternatives, or when symptoms have been controlled and the treating clinician is considering tapering therapies, Villa-Forte said.

Given the heterogeneity with which vasculitis can present, the value of diagnostic tests across specific phenotypes, and the potential for severe disease and complications, Villa-Forte suggested that specialists overall, particularly those at a dedicated center, “can help at any point in the care of patients with vasculitis.”

There are guidelines for the management of vasculitis from the American College of Rheumatology and the European Alliance of Associations for Rheumatology (see here and here), but these are specific to subtypes, such as ANCA-associated vasculitis or giant cell arteritis. For more information, Villa-Forte suggested a case-based learning model created by the Vasculitis Foundation and launched by the Project ECHO network.

Villa-Forte reported having a financial relationship with Amgen.

Ted Bosworth, a career medical writer based in New York City, has been covering advances in clinical medicine, including cardiology, for several decades.