Granuloma annulare


A benign inflammatory dermatosis.

Seen in all races, ethnic groups and geographic areas.

Women involved twice as often as men.

Rare in infancy, but otherwise occurs in all age groups.

Relatively common disease.

Characterized by skin papules, and annular plaques.

Cause is unknown.

It can follow viral infections, insect bites, TB skin test, cell-mediated hypersensitivity reactions, trauma, vitamin D excess, and UV light exposure.

A relatively uncommon inflammatory dermal process, named for the palisaded granulomas seen on histopathology and the annular appearance of the lesions clinically.

Several forms exist, including a localized form which is more common on the dorsal surface of the hands and feet.

A generalized form with subcutaneous involvement that is more common in children on the lower limbs.

Lesions usually disappear spontaneously within several months-several years.

Lesions may be palpable.

Lesions may persist for more than eight years in up to 25% of patients.

While lesions are self-limited they can recur.

Generalized form may have a relationship with type I diabetes mellitus, but data is not conclusive.

Occurs in up to 10% of adults with diabetes.

Iritis, sarcoidosis, autoimmune thyroiditis and neoplasms are associated diseases.

Disseminated disease presents as multiple skin colored or erythematous papules that can fuse to form annular rings.

Dyslipidemia is associated with granuloma annulare.

Granuloma annulare lesions may resolve after treatment of hyperlipidemia.

Histological exam shows degenerative collagen and palisaded granulomatous inflammation.

Localized disease has violaceous lesions up to 5 cm in diamter.

Localized Ga most common form of the process.

While most lesions occur locally, they can also be subcutaneous, perforating, macular, and disseminated.

Lesions tend to improve during the winter and worsen during the summer.

Localized GA most commonly found in children and adults younger than 30 years of age.

Annular rings with solidary papules or nodules may be associated.

Localized GA seen frequently on the feet, ankles, lower extremities and wrists.

Typically, granuloma annulare is asymptomatic and does not affect the face.

Generalized GA occurs mainly in adults.

Generalized GA accounts for 9-15% of cases.

Generalized GA usully involves the trunk, neck, extremties, face, scalp, palms and soles.

Generalized GA manifest with a wide range of lesions including papules, annular plaques, discolored patches of skin with yellow to violaceous.

Macular variants tend to arise on the feet, ankles, and thighs.

Individual lesions are typically between one and 4 cm in diameter, but can be much larger.

Generalized GA has a bimodal distribution, occurring in patients younger than 10 years and patients 30-60 years.

Subcutaneous GA occurs predominantly in children asymptomatic nodules in the subcutaneous tissues ranging from 5-4 cm in diameter and commonly on the anterior tibial plateau, ankles, buttocks, scalp, hands, eyelids, and dorsum of the feet.

Subcutaneous GA is predominantly a disease of healthy children typically 2-10 years of age, but can occur in adults.

A rare form of this process is perforating GA which is associated with superficial umbilicated papules usually involving the dorsum of the hands and fingers, but may be generalized to the trunk and extremities.

Perforating GA lesions generally heal with scarring.

Perforating GA has a prevalence of 5% of cases.

Perforating GA typically occurs in children.

Arcuate dermal erythema GA is associated infiltration erythematous patches with a large, hyperpigmented rings with central clearing.

Proposed pathophysiology include cell-mediated immunity, complex vasculitis, tissue monocyte abnormalities, connective tissue degeneration, lymphocyte mediated immune reaction, and cytokine mediated connective tissue degeneration.

Vast majority of cases occur in patients who are healthy.

Hypothesized to be associated with tuberculosis, insect bites, trauma, sun exposure, thyroiditis, vaccinations, and viral infections, including HIV, Epstein-Barr virus, hepatitis B virus, hepatitis C virus, and herpes zoster virus.

Familial cases have been observed in identical twins and siblings and an association with HLA phenotypes, suggest the possibility of a hereditary component.

HLA-B8 level increased in localized granuloma annulare, and HLA-A29 and HLA-BW35 levels are reported to be increased in generalized granuloma annulare.

Has some predilection for the sun-exposed areas and photodamaged skin.

Biopsy reveals necrobiosis, mucin deposition, a normal epidermis, and lack of plasma cells.

Photosensitive granuloma annulare has been found in association with HIV infection.

Some cases associated with ACE inhibitors, allopurinol, amlodipine, calcitonin, calcium channel blockers, diclofenac, daclizumab, and quinidine

Associated with type I diabetes mellitus.

Rarely associated with type II diabetes mellitus and thyroid disease.

Lesions are usually asymptomatic, with a localized or generalized.

Lesions may improve in winter and worsen in the summer.

Subcutaneous GA usually manifests as a large soft tissue mass, that may rapidly enlarge over a short period of time.

Examination usually reveals groups of 1-2 mm papules that range and color from normal to erythematous.

Lesions are often annular in arrangement.

Localized granuloma annulare usually not symptomatic and it has a tendency towards spontaneous resolution.

Localized lesions can been treated with topical corticosteroids with or without occlusion.

Intralesional corticosteroids may be utilized.

Cryotherapy using liquid nitrogen or nitrous oxide as refrigerants are effective treatments for localized granuloma annulare.

Laser, surgical excision, pentoxifylline, vitamin E, antimalarial‘s, alkylating agents, nonsteroidal anti-inflammatory drugs, radiation have been tried.

Psoralen-UVA, isoretinoin, dapsone, and Antituberculous medications have also been used successfully.

Other agents in both localized and generalized granuloma annulare involve tacrolimus, pimecrolimus and imiquimod cream.

Generalized granuloma annulare tends to be more persistent and severe.

In generalized granuloma annulare use of isotretinoin or phototherapy with oral psoralen and UV-A (PUVA) are acceptible options.

Methyl aminolevulinate photodynamic therapy has moderate success with photodynamic therapy using 20% 5-aminolevulinic acid (ALA) gel.

Recalcitrant disease has been treated with monthly combination therapy including rifampin at 600 mg, ofloxacin at 400 mg, and minocycline hydrochloride at 100 mg monthly for 3 months.

Anecdotal reports of successful treatment with adalimumab, cyclosporine, dapsone, efalizumab, etanercept, fumaric esters, hydroxychloroquine,infliximab, interferon-gamma, nicotinamide, pentoxifylline, and systemic steroids.

Initial therapy for localized granuloma annulare include intralesional corticosteroids, potent topical corticosteroids alone or under occlusion, and cryotherapy.

Reassurance and observation or generally sufficient therapy come to hasten resolution intralesional and topical corticosteroids may be tried but there may be secondary atrophy, telangiectasia and pigmentary changes.

Differential diagnosis: tinea, nummular eczema, pityriasis rosea, urticaria, erythema chronicum migrans, and erythema multiforme.

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