Granuloma annulare of the palms
1. Baylor College of Medicine, Houston, Texas. firstname.lastname@example.org
Granuloma annulare (GA) is a common, benign skin condition, which was first described over a century ago, but still remains an enigma with respect to etiology, associated systemic diseases, and treatment. A number of clinical variants have been classified. We report an atypical presentation of GA localized to the palms.
A 78-year-old woman was seen for evaluation of a 1-month history of pink-red papules and annular plaques on the palms that developed over approximately one week. She reported that most were asymptomatic but some were painful, especially with pressure. She was otherwise in her usual state of health and denied fevers, chills, cough, fatigue, malaise, or arthralgias. Her past medical history was significant for hypertension, hypercholesterolemia, sick sinus syndrome requiring pacemaker placement, Alzheimer disease, and stroke. Her medications included amlodipine, donepezil, simvastatin, sotalol, and aspirin, all of which she had been taking for years.
Examination of the skin revealed erythematous to violaceous indurated papules and annular plaques on the palms and fingers. No rashes or similar appearing skin lesions were noted elsewhere. Physical examination by her primary care physician revealed no unusual or notable changes from her baseline. The results of a complete blood count, serum chemistries, liver function tests, coccidioidomycosis serology, and chest x-ray were also normal.
Histopathological examination of a 4 mm punch biopsy specimen of the palm revealed orthokeratosis and an unremarkable epidermis. In the mid dermis, an interstitial lymphohistiocytic inflammatory infiltrate and focal increased mucin deposition were noted.
Treatment and follow-up
No specific treatment was initiated, as the lesions were only mildly symptomatic. She was referred back to her primary care physician for close clinical surveillance.
Granuloma annulare (GA) is a benign, relatively common cutaneous disease that classically presents as localized clusters of small papules that coalesce into arciform and annular plaques. It often occurs symmetrically, favoring acral sites such as the dorsum of the hands, elbows, and feet. Lesions are typically asymptomatic and range in color from skin-colored to violaceous. Granuloma annulare shows no known predilection for race or ethnicity and occurs in all age groups. However, 66 percent of patients are under 30 years of age and it is approximately twice as common in females than males . Numerous clinical variants of GA have been described with overlap including generalized, papular, nodular, patch, and subcutaneous GA.
Proposed pathogenic mechanisms for GA are many. Existing theories include type IV delayed type hypersensitivity , Th1 inflammatory reaction with IFN-γ-producing lymphocytes , lymphocyte-mediated activation of monocytes , and elastic tissue injury as the primary alteration . Numerous associations have been cited through the decades, including insect bites, trauma, TB testing, sunlight , and viral infections including HSV, EBV, HBV, HCV, and HIV [7-11]. However, these suggested etiologic factors currently remain unproven. Although a link between systemic disease, most namely diabetes mellitus (DM), and GA has been reported, no definitive evidence of a relationship exists. A retrospective study out of Mayo Clinic reviewed 32 patients with a 20-year follow-up of their GA and failed to reveal a statistically significant increase in any systemic diseases .
Although the occurrence of GA on the dorsum of the hands is frequent, involvement of the palms appears to be rare. Only a few cases have been previously reported, most often as painful acral papules [13-17]. Two pediatric cases of the subcutaneous variant of GA also exist [18, 19]. Of the cases of GA on the palms that we reviewed, one case involved a woman with dermatomyositis who developed a solitary lesion of GA on the palm . Brey et al presented 4 patients with acute onset acral papules of GA, 2 of whom had lesions involving the palm. Two of their 4 patients developed concomitant arthralgias and were evaluated extensively for rheumatologic disease, but were found not to meet criteria for any . Painful lesions of GA on the palm and soles were also noted in three of thirteen patients with GA and lymphoma evaluated in a retrospective study by Barksdale et al, leading the authors to conclude that atypical presentations, such as involvement on the palms and soles, may be associated with an underlying hematopoietic malignancy . Whereas GA has not been consistently linked to systemic disease , conditions such as interstitial granulomatous dermatitis with arthritis, palisaded neutrophilic and granulomatous dermatitis, rheumatoid papules, and Churg-Strauss granulomas, which all can clinically and histologically overlap with GA, belong to a spectrum of granulomatous diseases thought to be an immune-mediated reaction to a number of underlying conditions, such as rheumatoid arthritis, collagen vascular disease, Wegener granulomatosis, and malignancy [21, 22, 23]. Our patient had no identifiable associated immune-mediated condition at the time of diagnosis or subsequent follow-up.
Coccidioidomycosis has also been reported to cause an interstitial granulomatous dermatitis (IGD). DiCaudo et al presented 5 cases of coccidioidomycosis in which febrile, acutely ill patients presented with GA-like papules . Because our patient resides in a coccidiodomycosis endemic area, consideration for an atypical presentation of the infection was entertained and excluded based on a lack of symptoms, a normal chest x-ray, and negative coccidiodomycosis serology.
Granulomatous drug reactions have been associated with a number of medications, including calcium channel blockers, ACE inhibitors, beta blockers, antidepressants, and anticonvulsants. These generally manifest with erythematous to violaceous GA-like plaques that characteristically involve the inner aspects of the arms, medial thighs, and intertriginous areas  and occur months to years after drug onset . The histologic pattern of interstitial granulomatous drug eruption shares some similarities with that of granuloma annulare. However, interstitial granulomatous drug eruption can be differentiated by the absence of any significant necrobiosis, the presence of vacuolar interface changes, and the variable lymphoid atypia, not seen in granuloma annulare .
Our patient was taking two drugs that have been implicated in granulomatous drug eruptions, the calcium channel blocker, amlodipine, as well as the beta blocker, sotalol. Interestingly, we did come across a report of a granulomatous drug reaction with GA-like lesions of the palms as well as the legs in a 64-year-old woman occurring 13 days after starting amlodopine and clearing within 3 months of drug cessation . Our patient, however, had been taking the same doses of sotalol for over 24 months and amlodipine for 22 months prior to the sudden onset of her skin lesions, making these a less likely cause of her eruption. She also lacked the extra palmar, intertriginous annular plaques that clinically typify interstitial granulomatous drug reactions. In addition, the histology did not show the associated findings of interface vacuolar changes and lymphoid atypia to support a diagnosis of IGDR.
Granuloma annulare of the palms appears to be rare, but it should be included in the differential diagnosis of palmar papules and plaques. Careful evaluation and exclusion of an interstitial granulomatous dermatitis associated with underlying conditions, such as rheumatologic disease, malignancies, coccidioidomycosis, or medications, are recommended.
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