Itchy leg bullae after a trip outdoors

The woman was diagnosed with bullous arthropod bite reaction (BABR). Arthropod bite reaction can produce a wide array of clinical lesions. The most characteristic reaction is erythematous edematous papules that are markedly pruritic and often excoriated.1 Occasionally, vesicles and bullae...

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The woman was diagnosed with bullous arthropod bite reaction (BABR). Arthropod bite reaction can produce a wide array of clinical lesions.

The most characteristic reaction is erythematous edematous papules that are markedly pruritic and often excoriated.¹ Occasionally, vesicles and bullae may develop in response to insect saliva in a previously sensitized individual.² There are no epidemiologic studies regarding the incidence or prevalence of BABR, nor are there any known risk factors based on ethnicity, gender, or age. There is, however, a well-accepted association of exaggerated arthropod reaction in individuals with chronic lymphocytic leukemia.³

It is often difficult to determine the culprit arthropod, as a vast majority of patients are unaware of the initial insect bite.³ However, certain arthropods have characteristic bite or reaction patterns. Bedbug (Cimex lectularius) bites are often noted in linear groups of three (commonly referred to as breakfast, lunch, and dinner).¹

Blister beetles (order Coleoptera) have caused epidemics of bullous skin disease in hospital wards worldwide.¹ Flea (order Siphonaptera) bites are usually located on the lower legs.

Scabies (Sarcoptes scabiei var. hominis) infestations may rarely cause a bullous reaction with characteristic involvement of the interdigital webbing of the hands, flexural wrists, axillae, waist, feet, buttocks, and belt area.¹

The differential diagnosis of tense bullae includes autoimmune blistering disorders, drug-induced bullous pemphigoid, contact dermatitis, bullosis diabeticorum, and edema bullae. Bullous pemphigoid (BP) is the most common autoimmune blistering disorder, with the vast majority of patients presenting after age 60 years. Although there is a rare variant localized to the pre-tibial area, most cases of BP have a symmetrical distribution, usually affecting the flexural limbs and abdomen.

Drug-induced BP must also be considered as a differential. Medications commonly implicated include furosemide (Delone, Furocot, Lasix, Lo-Aqua), ibuprofen, phenacetin, d-penicillamine (Cuprimine, Depen), ampicillin (Omnipen, Polycillin, Principen), penicillin derivatives, and captopril (Capoten).⁴ A careful review of the patient’s medication list is imperative, but such a review can be challenging, as the time from initiation of medication to bullae development is variable.

Acute allergic contact dermatitis (ACD) may also present with tense bullae; however, these lesions will almost invariably develop in an erythematous background. One of the most common allergens that cause acute ACD is the OTC antibacterial Neosporin. Clinicians should specifically inquire about its use because patients often fail to mention it due to its ubiquity.

Bullosis diabeticorum is a rare manifestation of diabetes and is also characterized by tense bullae most commonly located on the feet. A helpful distinguishing feature is the general lack of symptoms in bullosis diabeticorum, unlike BABR, which is most often pruritic. Finally, the differential diagnosis can include edema bullae; by definition, however, pitting edema must be present for this diagnosis.

BABR can sometimes be diagnosed clinically. A thorough history regarding potential exposures (e.g., outdoor activities, pets, home infestations) must be obtained. A comprehensive physical exam should also be performed to assess for areas of involvement and to look for stigmata of such underlying causes as lymphadenopathy and peripheral edema. A detailed medication history should also be obtained, including use of such OTC medications as Neosporin and ibuprofen, which patients often fail to report.

In a healthy young patient on no medications with a suggestive history (i.e., recent outdoor exposure or known arthropod infestation), the diagnosis sometimes can be made on clinical grounds. However, in many cases, two biopsies are required for hematoxylin and eosin (H&E) and direct immunofluorescence (DIF) to rule out other etiologies, including autoimmune bullous conditions, which will have a positive DIF.

Treatment is supportive, as BABR will resolve with time. Pruritus can be managed with topical corticosteroids. Class 1 topical corticosteroids (e.g., clobetasol 0.05% ointment) are usually necessary to control pruritus on the extremities. Class 1 topical corticosteroids are a relative—but not absolute—contraindication on the face, so a less potent class is recommended.

Antihistamines, including diphenhydramine and hydroxyzine, are helpful adjuncts for controlling pruritus. If the bullae are painful or located on the feet and interfering with ambulation, the fluid can be aspirated with a sterile needle in the clinic.

Alternatively, patients can puncture the bullae at home with a sterilized needle to release the fluid. Instruct patients to leave the roof of the bullae intact to prevent open erosions, which can be a nidus for infection.

This woman’s history was notable for recent outdoor exposure. Although she had recently started colestipol, a literature review revealed no association with drug-induced BP. None of the woman’s antihypertensives were commonly associated with drug-induced BP. Although the history and distribution of her lesions was suggestive of an arthropod reaction, her age and history of diabetes precluded making a diagnosis on clinical grounds alone.

Two biopsies were obtained; a lesional biopsy for H&E was notable for an intraepidermal vesicle with spongiosis and eosinophils, and a perilesional biopsy for DIF was negative.

Taken together, these findings were consistent with BABR. A normal complete blood count ruled out an underlying lymphoproliferative disorder. The woman was managed with antihistamines and topical corticosteroids for symptomatic relief.

Audrey Chan, MD, is a resident in the Department of  Dermatology at Baylor College of Medicine in Houston.