Resistant urticaria requires adjunctive treatments

Key Points

"For several years, we've been trying to understand a group of patients with CIU who do not respond well to treatment with antihistamines," says Michael D. Tharp, M.D., the Clark W. Finnerud professor and chairman, department of dermatology, Rush University, Chicago.

In most studies of chronic urticaria, he says, "Antihistamines will give a good to excellent result in 65 to 70 percent of the population," which leaves 30 percent to 35 percent who get suboptimal results. "Every dermatologist in practice has these patients who don't seem to be very antihistamine-responsive."

However, in an earlier report, skin biopsies of seven of his female patients with chronic, antihistamine-resistant urticaria showed a type of inflammatory-cell infiltrate that was more rich in neutrophils and eosinophils than lymphocytes, a subtype that he and a colleague proposed calling polymorphonuclear cell-predominant urticaria (PPU) (Zavadak D, Tharp MD. Immunol Allergy ClinicsNA. 1995;15(4):745-759).

Study details

In this study, 57 percent of patients experienced angioedema; 42 percent had individual lesions lasting more than 24 hours; and 30 percent experienced arthralgias. And because only about 12 percent of study patients responded to antihistamines, Drs. Tharp and Zavadak hypothesized that patients with chronic PPU would need treatment with additional agents.

"We proposed that these patients who were resistant to antihistamines appeared to manifest the histologic skin findings similar to the early component of a late-phase reaction that occurs in patients receiving allergy shots," Dr. Tharp adds. During this reaction, he explains, what starts as a neutrophil- and eosinophilic-rich infiltrate (appearing after an allergy injection) within two to eight hours turns after 24 to 48 hours into a lymphocyte-rich infiltrate.

"In that original report," Dr. Tharp says, "most of the patients responded to antihistamines plus colchicine." An older medication with anti-inflammatory properties that's used in treating gout, colchicine also limits the migration of neutrophils and eosinophils in the skin, he says.

LPU characteristics

Characteristics of LPU include itching, while patients with PPU experience itching, plus burning and stinging, Dr. Tharp says. "For most people with PPU, individual lesions often last longer than 24 hours," which is rarely the case with LPU, he adds. "Patients with LPU don't seem to have many other complaints, but patients with PPU sometimes will complain of muscle and joint aches."

Histologically, both LPU and PPU show edema, he says. "Both show dilation of blood vessels," Dr. Tharp adds, "but the histology shows that in LPU, lymphocytes are the predominant infiltrate, whereas there are many more eosinophils and neutrophils without evidence of vasculitis in the PPU group - about threefold more per high-powered field."

A more recent study involving Dr. Tharp's patients at Rush University explores treatment responses of patients with PPU (Tharp MD, Haugen R. Unpublished). More specifically, Dr. Tharp and his colleague evaluated 77 patients who were referred to the Rush University Department of Dermatology with chronic, antihistamine-resistant urticaria for inclusion in this study.

Inclusion criteria

Inclusion criteria included availability for at least four weeks for evaluation and a history of at least one skin biopsy. Investigators excluded patients with no biopsy available for review, presence of vasculitis on biopsy or insufficient availability for follow-up.

For the 43 patients who met study inclusion criteria, investigators who were blinded to patient histories and clinical exam results evaluated each biopsy sample and characterized the makeup of its infiltrate. They also treated patients with regimens including a multiple-antihistamine regimen or antihistamines plus dapsone and/or colchicine.

Overall, Dr. Tharp says, 86 percent of patients who were referred for treatment-resistant CIU responded to this combined treatment regimen. Patients with antihistamine-resistant lesions also were likely to experience burning/stinging, arthralgias, increased numbers of neutrophils in lesional skin, thyroid abnormalities and good response to colchicine and/or dapsone, he adds. DT

Disclosure: Dr. Tharp reports no relevant financial interests.