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Case Note

Case Note: Annular Eruption on the Hands

History

A 38-year-old male, with no significant past medical history, presents for management of asymptomatic papules on the hands.

Initial evaluation

  • Healthy-appearing male
  • Social history is unremarkable
  • Presents for evaluation and management of asymptomatic, fine, flesh-to-pink-colored papules on the bilateral dorsal hands
    • Papules are numerous, minute, pinpoint, erythematous, and are grouped into an annular ring
    • Patient was previously treated with over-the-counter antifungals with no response
  • Review of systems reveals no complaints, including no joint pain, fevers, arthritis, eye symptoms, or recent illness
  • There is no lymphadenopathy or hepatosplenomegaly on exam
  • Image 1
    Image 1

Enter your diagnosis

Diagnosis

  • A diagnosis of granuloma annulare (GA) is rendered

Initial Treatment

  • Potassium hydroxide scraping taken to evaluate for presence of dermatophyte infestation
    • Ruling out tinea
  • Biopsy of representative skin lesion performed to confirm diagnosis
  • Routine blood work performed, including complete blood count (CBC) and comprehensive analysis of metabolic profile
  • Thorough review conducted of social history, exposures, and behaviors to evaluate for any high-risk sexual behaviors
  • Treatment with high-potency topical corticosteroids is initiated

Follow-up evaluation strategy

Follow-up evaluation:

  • Biopsy is interpreted as consistent with GA
  • Patient reports no improvement with topical corticosteroids
  • Therapy with intralesional corticosteroid injections is initiated
    • Patient notes a good response over subsequent visits

First-line therapy:

  • For limited disease, topical corticosteroids may help, but intralesional injections of corticosteroids are often required. More widespread disease should be treated with either antimalarial drugs or phototherapy (generally psoralen combined with ultraviolet A [PUVA])
    • Topical corticosteroids may include a short course of clobetasol 0.05% to individual lesions on extremities)
    • Intralesional injections may include triamcinolone (strength varying by anatomic site and size/depth of lesion; generally 10-20 mg/mL)
  • Watchful waiting may be a reasonable treatment strategy in many patients

Subsequent treatment steps:

  • More widespread disease often requires antimalarial therapy (hydroxychloroquine 200 mg twice daily or up to 6.5 mg/kg/day dosing) or phototherapy (PUVA three times weekly)
  • Non-responders may warrant alternative treatment options, of which there is a wide range, with varying mechanisms, risks, benefits, and generally limited data supporting most alternative treatments
  • Alternative options include: systemic retinoids, combination antibiotic therapy (including rifampin/oxacillin/minocycline), dapsone, potassium iodide solution, systemic corticosteroids, alternate immunosuppressive agents, and combination therapy
  • Targeted therapy with specific lasers (including pulsed dye laser [PDL] treatment), cryosurgical destruction, and repeated intralesional injections may lead to improvement in treated areas in some cases
  • Patients with the most severe disease may be candidates for treatment with tumor necrosis factor (TNF)-α inhibitors, particularly infliximab or adalimumab, but data on their use is just emerging and it is essential to weigh the risks and benefits

General discussion

GA is a relatively common inflammatory skin condition, which can manifest with cutaneous eruptions in a handful of patterns. First described in 1895 as 'ringed eruption', the term 'GA' was initially proposed in the early 1900s to describe the annular, ring-like nature of this distinctive eruption. While GA is commonly encountered by dermatologists clinically (0.1-0.4% of new visits to dermatologists were for GA in one small study), robust epidemiologic studies are lacking and the true incidence is unknown. GA tends to occur in the third to fifth decade of life, with a roughly equal female to male ratio with perhaps a slight female predominance. The rates of specific GA subtypes (see below) may vary slightly by age group.

GA most typically presents as localized granuloma annulare (LGA), single or few annular (ring-like, circular), pink-erythematous, thin plaques over the dorsal hands or feet. Generalized granuloma annulare (GGA) is the next most common presentation, which can either include widespread annular plaques, patches, or disseminated, small, erythematous, firm papules, distributed widely over the trunk and extremities. Subcutaneous GA (SGA) is rare in adults, but is the most common type in children, and presents with firm painless subcutaneous nodules (which may have more typical GA overlying the skin above the nodule) usually on the lower limbs. A number of rare presentations of GA have been described including, in particular, perforating GA (papules with central plugs of connective tissue extruding through the epidermis), palmar/plantar GA, linear/blaschkoid GA; these manifestations are rare. GA may rarely be photodistributed; such cases share considerable overlap with an entity termed 'annular elastolytic giant cell granuloma' (AEGCG), which tends to present with annular erythematous plaques with a thin palpable rim and central atrophy with lesions limited to the head and sun-exposed areas. Many consider AEGCG simply a subtype of GA. The differential diagnosis of GA typically includes tinea infection (which often presents with annular lesions on the dorsal hands as well, although tinea tends to have scale, whereas GA usually does not), sarcoidosis, other reactive granulomatous eruptions (such as palisaded neutrophilic and granulomatous dermatitis [PNGG] and interstitial granulomatous dermatitis [IGD]), necrobiosis lipoidica, and for SGA, rheumatoid nodules.

The etiopathogenesis of GA remains unknown. There are limited data regarding a genetic/inheritable risk for GA, although single case reports and small case series have identified siblings and first-degree relatives with GA in some patients. One report identified identical twins who developed GA with the HLA-AH8.1 mutation, and HLA-Bw35 has been reported as potentially conferring risk for GGA, however, these studies are quite small and limited in scope. The triggering event that generates the cutaneous granulomatous inflammatory response has yet to be elucidated. Some have hypothesized that blood vessel damage - potentially via immune complex deposition - may trigger a reactive inflammatory response; this hypothesis has been suggested for similar reactive granulomatous processes in the skin (such as palisaded neutrophilic and granulomatous dermatitis or interstitial granulomatous dermatitis). Others have suggested that GA represents a delayed hypersensitivity response to an unidentified host antigen, perhaps abnormal collagen bundles or elastic fibers. Another theory proposed that abnormal neutrophil function and migration may lead to increased macrophage response and granuloma formation. Many have sought an infectious etiology, as there have been reports of GA in the setting of viral hepatitis and following some vaccines. GA may occur in response to cutaneous injury as an isotopic response, including following lightning strike, tattoo placement, bug bites, and after vaccination. Medication-induced GA is not as widely reported as other forms of medication-induced reactive granulomatous processes, however, drug-induced forms do exist in isolated case reports, including following treatment with TNF- α inhibitors, gold therapy, and interferon.

GA is frequently asymptomatic, but patients often request treatment as the lesions are frequently found on exposed sites (such as the dorsal hands), and GGA may be symptomatically bothersome in some cases. Notably, many patients with GA will spontaneously improve within a few years of disease onset. However, recurrences (whether following spontaneous remission or treatment response) are common, occurring in up to 40% of cases. It is essential to appropriately counsel patients that the disease is often recalcitrant to therapy, may self-resolve, and can unpredictably return.

Regardless of the clinical type, when diagnosing GA, physicians should be aware of potential disease associations. Most of the data surrounding GA and potential associated diseases comes from small, retrospective studies, with large-scale epidemiologic studies lacking. With that caveat, there is a growing literature suggesting a potential association between GA and diabetes. Given diabetes is seen in conjunction with a roughly similar (granulomatous) skin condition, necrobiosis lipoidica, and the ease of screening involved, it is worth evaluating patients with GA for occult diabetes. Other potential disease associations include dyslipidemia and thyroid disease. Again, while the data is based on small studies, screening for these conditions is relatively low cost and low risk, and is worth offering to patients with a new diagnosis of GA. Rare reports exist linking GA with malignancies, particularly lymphoproliferative/hematopoietic malignancies, and beyond age-appropriate malignancy screening, patients with GA likely warrant at least a CBC, and, if atypical features are present, potentially further testing.

Treatment of GA is challenging. Once again, treatment recommendations are somewhat limited by the lack of robust evidence or large trials. Compounding this, many patients with GA will spontaneously improve after a few years, making study interpretation challenging. Patients with limited disease (usually localized GA) will often respond to intralesional corticosteroid injections. Patients with more widespread disease may respond to either antimalarial therapy or phototherapy, particularly PUVA or UVA-1. Evidence for other therapeutic options is limited to a very small number of cases. Alternative therapies include dapsone, saturated solution of potassium iodide, selected lasers (PDL, excimer), cryotherapy, TNF- α inhibitors, fumaric acid esters, anti-inflammatory antibiotics (tetracycline class agents), rifampin-ofloxacin-minocycline combination therapy, allopurinol, cyclosporine, methotrexate, systemic retinoids, and more. Experienced physicians counsel patients that any given therapy has about a 1 in 3 chance of improving GA and that even with treatment response it is important to remember that a significant number of patients will experience relapse and recurrence of skin lesions.

Further reading

Avitan-Hersh E, Sprecher H, Ramon M, Bergman R. Does infection play a role in the pathogenesis of granuloma annulare? J Am Acad Dermatol 2013;68:342-3.

Dabski K, Winkelmann RK. Generalized granuloma annulare: histopathology and immunopathology. Systemic review of 100 cases and comparison with localized granuloma annulare. J Am Acad Dermatol 1989;20:28-39.

Piette EW, Rosenbach M. Granuloma annulare: a comprehensive review and update for the dermatologist. J Am Acad Dermatol. In Press.

Requena L, Fernandez-Figueras MT. Subcutaneous granuloma annulare. Semin Cutan Med Surg 2007;26:96-9.

Thornsberry LA, English JC 3rd. Etiology, diagnosis, and therapeutic management of granuloma annulare: an update. Am J Clin Dermatol 2013;14:279-90.

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