Pyoderma gangrenosum presentation differs with age

Reuters Health Information: Pyoderma gangrenosum presentation differs with age

Pyoderma gangrenosum presentation differs with age

Last Updated: 2018-02-20

By Will Boggs MD

NEW YORK (Reuters Health) - The clinical manifestation and comorbidities of pyoderma gangrenosum (PG) differ between patients under age 65 and older patients, according to a retrospective study.

"Our study really emphasizes that younger patients and older patients are quite different," Dr. Misha Rosenbach from Perelman School of Medicine at the University of Pennsylvania, in Philadelphia, told Reuters Health by email. "Younger patients have a much stronger association with inflammatory bowel disease (IBD), and older patients with hematological disorders."

Pyoderma gangrenosum, a rare inflammatory neutrophilic dermatosis, is characterized by the development of sterile inflammatory pustules that expand rapidly into ulcers with violaceous, undermined borders. PG is often associated with medical comorbidities.

Dr. Rosenbach and colleagues examined the effect of age on the clinical presentation and associated comorbidities of PG. They used data from the electronic health records of 243 patients from Brigham and Women's Hospital, Massachusetts General Hospital, and the University of Pennsylvania Health System.

The patients' median age at presentation was 51.6, and 68.3% were younger than 65, according to the February 14 JAMA Dermatology online report.

The only clinical feature that differed by age was pathergy - the phenomenon of developing new or worsening lesions after trauma to the skin - which was more common among patients age 65 or older (36.3%) than among younger patients (24.3%). Location of lesions, multi-focality, and other clinical features were similar between patients in the younger and older age groups.

Most patients (66.3%) had an associated comorbidity, including IBD in 41.0%, inflammatory arthritides in 20.5%, solid-organ malignant disease in 6.5%, hematologic malignant disease in 5.9%, and hematologic disorders in 4.8%.

A similar proportion of patients in each age group had an associated comorbidity, but the specific associated diseases varied significantly by age.

IBD was more common among patients younger than 65 (47.7%) than older patients (26.6%). In contrast, older patients were more likely to have rheumatoid arthritis (13.3% vs. 6.2%), solid-organ malignant neoplasms (13.3% vs. 3.3%), hematologic malignant neoplasms (9.7% vs. 4.1%), and hematologic disorders such as monoclonal gammopathy of uncertain significance (MGUS), myelodysplastic syndrome, and polycythemia vera (10.6% vs. 2.1%).

Given these findings, the authors propose an age-focused workup of patients presenting with PG.

"Young patients with PG really need an evaluation for IBD, and older patients with PG should get not just a CBC with differential, but also evaluation for monoclonal gammopathy, and a low threshold for a referral to a hematologist," Dr. Rosenbach said.

"PG is a complicated disease," he added. "We see far too often patients with venous leg ulcers (which can be hard to heal) diagnosed with PG, or patients with PG who are treated with steroids for many years, in the absence of inflammation, simply because the ulcer left by the PG is still present (though the inflammation is gone)."

"I would hope physicians realize that PG is an approachable, manageable, and treatable disease, but one that requires a careful, thorough evaluation, and close monitoring, with a low threshold to refer to experienced medical dermatologists," Dr. Rosenbach concluded.

Dr. William Huang from Wake Forest School of Medicine, Winston-Salem, North Carolina, who recently reviewed the pathogenesis and treatment of PG, told Reuters Health by email, "Although the typical rate of association of PG with systemic disease (IBD, inflammatory arthritis, and hematological disorders) has traditionally been taught as 30% to 50%, research from this group as well as ours has suggested that the rate may be much higher."

"Patients with a confirmed diagnosis of PG should be screened for associated systemic disease based on a thorough history and physical exam due to the high rate of association," he said.

"Managing patients with PG provides an opportunity for dermatologists to work alongside our colleagues in other medical specialties, as PG may be the initial presenting sign of an associated condition, such as inflammatory bowel disease, inflammatory arthritis, and hematological disorders, and available therapies may be able to control both their cutaneous and internal disease," Dr. Huang said.

In a related article, Dr. Emanual M. Maverakis from the University of California, Davis, and colleagues describe a set of diagnostic criteria of ulcerative pyoderma gangrenosum developed through a Delphi consensus of international experts.

According to the consensus, ulcerative PG should be diagnosed based on one major criterion (biopsy of ulcer edge demonstrating neutrophilic infiltrate) and eight minor criteria: exclusion of infection; pathergy; history of IBD or inflammatory arthritis; history of papule, pustule, or vesicle ulcerating within 4 days of appearing; peripheral erythema, undermining border, and tenderness at ulceration site; multiple ulcerations, at least one on an anterior lower leg; cribriform or "wrinkled paper" scar(s) at healed ulcer sites; and decreased ulcer size within 1 month of initiating immunosuppressive medication(s).

Combining the major criteria with four of eight minor criteria maximized discrimination between PG and its mimics, with 86% sensitivity and 90% specificity.

"PG has been reported to be associated with some cancers and hematologic disorders," Dr. Maverakis told Reuters Health by email. "No consensus was reached on the usefulness of such co-existing conditions in making a diagnosis of PG. I think the reason must have been that these conditions are relatively rare in PG when compared to other coexisting conditions."

"There have been very few trials in PG, and hopefully these diagnostic criteria will aid investigators in clinical trial design, especially in terms of inclusion criteria," he said.

"PG is not a diagnosis of exclusion," Dr. Maverakis concluded.

"Ultimately, this is a tremendous step forward, and it very likely offers high internal validity for the purposes of clinical trials, but there is the risk of low external validity, particularly if only 12% of patients in clinical practice would meet the major criterion," write Dr. Benjamin H. Kaffenberger and Dr. John Trinidad from Ohio State University, Columbus, in a related editorial.

"I don't think (the criteria) are quite ready for prime time yet," Dr. Kaffenberger added by email. "It will be very important to revalidate them in clinical practice, a process that I hope will occur."


JAMA Dermatol 2018.

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