Chronic Urticaria Associated With Helicobacter pylori Infection

Author:
Andrew Krispinsky, MD
United States Navy, Portsmouth, Virginia

Citation:
Krispinsky A. Chronic urticaria associated with Helicobacter pylori infection. Consultant. 2018;58(2):90-92.

A 41-year-old man with no significant medical history presented to his primary care provider with an 11-day history of an intensely pruritic rash. The patient had first noticed a few pruritic papules on his lower back after having worked on his lawnmower; over the subsequent week, the rash then had spread to his bilateral flanks, buttocks, and lower extremities (Figures 1 and 2). He reported that the lesions would come and go within a few days. His palms, soles, genitals, and head were spared.

Figure 1: Multiple erythematous papules and macules were present on the patient’s right flank at initial presentation.

Figure 2: Prominent areas of purpura with central dusky hyperpigmentation, many of which were targetoid, were present on the patient’s right thigh at initial presentation.

History. The patient denied any recent illnesses, new medications, recent travel, sick contacts, or a history of herpes simplex virus infection. He reported a 21-year history of heavy smokeless tobacco use. He denied fever, chills, fatigue, night sweats, unintentional weight loss, or any other pertinent symptoms.

NEXT: Physical examination, treatment, and referral

Physical examination. Numerous erythematous macules, patches, papules, and plaques were present on his torso, buttocks, and thighs, along with prominent areas of purpura with central dusky hyperpigmentation, many of which were targetoid. The rest of the physical examination findings were unremarkable.

Treatment and referral. The patient was started on a 1 mg/kg prednisone taper, as well as cetirizine, 10 mg twice daily, and hydroxyzine, 50 mg before bed. At a follow-up visit 1 week later, the eruption had progressively worsened (Figure 3). The working diagnosis at that time was urticarial vasculitis. Other diagnoses in the differential were atypical erythema multiforme, pigmented purpura, and paraneoplastic dermatosis. The patient was referred to a dermatologist for further testing.

Figure 3: At the 1-week follow-up visit, the lesions on patient’s right flank had enlarged and evolved to prominent hyperpigmented patches with a targetoid appearance.

At his initial visit with the dermatologist, the patient reported moderate improvement of the pruritus with a continuing cycle of eruption and resolution of new lesions. During this encounter, he reported having a 2-month history of early satiety, bloating, and increased frequency of bowel movements. His diffuse eruption coupled with a history of tobacco use and gastrointestinal (GI) tract symptoms raised greater concern for a paraneoplastic etiology.

NEXT: Diagnostic tests and discussion

Diagnostic tests. The results of extensive laboratory tests, including a complete blood cell count, a comprehensive metabolic panel, erythrocyte sedimentation rate, complement tests, urinalysis, blood cultures, an antinuclear antibody test, and a hepatitis panel, were unremarkable.

Results of direct immunofluorescence testing of a biopsy specimen were unremarkable, ruling out a vasculitic process. Pathology testing with hematoxylin-eosin staining revealed superficial perivascular dermatitis with red blood cell extravasation, findings consistent with an urticarial reaction. The patient was instructed to extend his prednisone taper, to continue twice-daily antihistamine dosing, and to follow up with his primary care provider regarding the GI tract symptoms.

At a follow-up visit 1 week later, the urticaria had stopped appearing on the patient’s torso, but new lesions were appearing on his arms and lower legs. Physical examination findings included abdominal distension and swelling of the neck and face. Serologic testing to evaluate his GI tract symptoms revealed active Helicobacter pylori infection.

Discussion. H pylori is a microaerophilic, spiral-shaped, gram-negative bacterial species that is linked to many GI tract diseases, including gastritis, peptic ulcer disease, lymphoma, and gastric carcinoma.¹ The worldwide incidence of H pylori infection has been estimated at roughly 50%,² with a much lower incidence of 7.5% in the United States.³

Diagnosis is made with the urea breath test, serology tests, and the stool antigen assay, depending on availability and the clinician’s familiarity with these tests. The possible relationship between H pylori infection and gastritis has been controversial; however, a distinct diagnosis of H pylori-associated gastritis recently was recommended by the faculty of a global consensus conference.⁴ The patient described here did not report any of the classic symptoms of gastritis, and subsequent esophagogastroduodenoscopy findings revealed no evidence of gastritis, ulcer, or malignancy.

Chronic urticaria (CU) is defined by the presence of urticaria during most days of the week for a period of 6 weeks or greater. It affects approximately 1% of the population.⁵ Urticaria can be the result of a physical stimulus or a known condition but in many cases is idiopathic. Autoimmune diseases, infection, and hypersensitivity to foods or drugs are important potential causes.⁵ First-line treatment is a second-generation antihistamine, with an increase to 4 times daily dosing and the use of short-term corticosteroids if the urticaria is unresponsive.⁶ 

CU is a known extraintestinal manifestation of H pylori infection, with a poorly understood pathophysiologic relationship. One theory is that chronic infection leads to increased secretion of pepsin and gastric acid, causing active inflammation with recruitment of neutrophils and eosinophils.⁷ Major basic protein can then be released by eosinophils and may cause mast cell degranulation with potential systemic signs such as an urticarial reaction.⁸

The evidence for the remission of CU following antibiotic therapy has been equivocal. However, successful eradication of H pylori, as determined by repeated testing after treatment, is more likely to result in resolution of CU compared with failed eradication.⁹ Due to an increased risk for malignancy and progressive disease in the GI tract, it is recommended that all patients who are H pylori-positive receive eradication therapy, even if they are asymptomatic.⁴

Given the prevalence of H pylori infection in the general population, it is important for clinicians to be familiar with atypical presentations and current treatment guidelines.

Outcome of the case. The patient received triple therapy with a twice-daily proton pump inhibitor, 1 g of amoxicillin, and 500 mg of clarithromycin, with subsequent resolution of urticaria and GI tract symptoms. 

References:

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7. Valsecchi R, Pigatto P. Chronic urticaria and Helicobacter pylori. Acta Derm Venereol. 1998;78(6):440-442.
8. O’Donnell MC, Ackerman SJ, Gleich GJ, Thomas LL. Activation of basophil and mast cell histamine release by eosinophil major basic protein. J Exp Med. 1983;157(6):1981-1991.
9. Federman DG, Kirsner RS, Moriarty JP, Concato J. The effect of antibiotic therapy for patients infected with Helicobacter pylori who have chronic urticaria. J Am Acad Dermatol. 2003;49(5):861-864.

DISCLAIMER:

The views expressed herein are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, the Department of Defense, or the US Government.