How To Detect And Treat Granuloma Annulare

By Gary L. Dockery, DPM, FACFAS

   Granuloma annulare (GA) is a benign inflammatory, self-limiting granulomatous dermatoses characterized by a variable clinical presentation of dermal and subcutaneous lesions. Although this condition may occur at any age, it is predominantly a disease of children ranging in age from 2 to 10 and adults who are younger than 30. GA is very common in young females as they are twice as likely to be affected than males. Foot involvement occurs in more than 70 percent of all patients with GA and hand involvement occurs in 60 percent of patients.    The lesions may spontaneously resolve in three months to many years, with the average remission occurring two years after onset. Recurrences are common but newer lesions tend to resolve sooner than the original lesions.    The cause of GA is unknown but traditionally has been hypothesized to be related to insect bites, sun exposure, viral infections, diabetes, thyroiditis and certain medications such as antibiotics, antiinflammatory agents and oral contraceptives. However, none of these suggested etiologic factors has been confirmed. Researchers have also proposed the possibility of a hereditary component in some cases but, again, the evidence is weak because of the low numbers of documented cases.

A Closer Look At The Clinical Variants Of Granuloma Annulare

   There are several clinical variants of GA including localized GA (classical type), subcutaneous GA, generalized GA (disseminated type), nodular GA and perforating GA.    Localized GA. Localized GA is the most common type and it occurs in both children and young adults under the age of 30. This type is characterized by skin-colored or violaceous, well defined, 1 to 2 mm papules. These papules may expand into larger lesions that are arranged in a complete or half-circle configuration, measuring from 1 to 5 cm in diameter. The lesions are most common on the dorsa of the hands and feet, and on the extensor aspects of the legs. The center of the lesions may be erythematous and slightly depressed relative to their borders. These lesions may be solitary or multiple, with over half of all patients presenting with a single lesion. These lesions may improve in winter and worsen in the summer.    Subcutaneous GA. Subcutaneous GA consists of solitary or multiple asymptomatic lesions measuring 1 to 5 mm in diameter. They may coalesce or expand to several centimeters. The soft tissue masses are usually stable for months but they may enlarge rapidly over a period of a few weeks. Palpation of the lesion reveals small firm granular bodies that are very mobile under the skin. One will commonly see subcutaneous GA on the dorsa of the hands and feet. The most commonly reported site of involvement is the lower extremities (65 percent of all cases). These lesions are often on the pretibial surface and top of the foot. Clinicians may also see this condition on the palms and fingers, legs, buttocks and scalp. The deep dermal lesions are attached to fascia and are often mobile. Some of the larger lesions may be pruritic in nature.    Generalized GA. Generalized or disseminated GA is characterized by numerous, widespread, skin-colored, pink or yellow/tan papules or nodules, which one will see on the trunk and all extremities. With this type of GA, it is common for the patient to have multiple lesions that are pruritic and these lesions may become circinate or reticular. Lesions may coalesce into annular plaques, which measure 3 to 6 cm in diameter and may enlarge centrifugally over several weeks. The patients are usually younger than 10 or older than 40. Biopsy is required for a confirmed diagnosis of GA, but it is generally not considered necessary because the clinical presentation is relatively consistent. A very interesting finding is that many lesions will spontaneously resolve after a sectional biopsy. It is not uncommon for the biopsied lesion to be totally gone by the time one receives the pathology report from the lab.    Nodular GA. Nodular GA is characterized by the presence of one or more superficial or deep nodules. One will see this most often in children younger than 18. In most cases, these nodules are firm, skin-colored and non-tender without overlying epidermal alterations. When the nodules are deep, they tend to be solitary and can be confused with juxtaarticular rheumatic nodules in children. In some cases, clinicians may see both subcutaneous and nodular GA together.    Perforating GA. Perforating GA is characterized by small, superficial, 1 to 4 mm skin-colored papules that may coalesce to form annular plaques. In some cases, several small perforations occur in each lesion and small central plugs or crusts may form. In a few patients, the erythematous papules may evolve into yellowish pustular lesions that subsequently exude a thick and creamy or clear and viscous fluid, forming crusting or scaling lesions that heal with atrophic or hyperpigmented scars. However, this is rare.    Larger and more ulcerated plaques are common among middle-aged and elderly female patients. They are also more common among patients with diabetes mellitus. These lesions tend to have a predilection for the dorsa of the hands and feet.

Key Diagnostic Principles

   While laboratory studies are not usually helpful in diagnosing GA, they may be helpful in ruling out other conditions (see “A Guide To Differential Diagnosis For Granuloma Annulare” below).    In most cases, the basic laboratory studies would include a CBC count, erythrocyte sedimentation rate and a rheumatoid factor study to assist in ruling out other possible conditions. When the patient presents with the classical presentation for GA and no other remarkable physical examination findings, other than the skin lesions, no further workup is usually necessary.    However, obtaining a biopsy of the skin lesion is very useful for making a positive diagnosis. Even though it is considered an unnecessary procedure by many, I almost always recommend getting a lesion biopsy. This prevents any second guessing of the diagnosis and enables one to provide very specifically directed treatment. When young children under the age of 8 present with GA, I tend to avoid getting the biopsy unless the condition worsens or does not resolve in a timely manner.    The histological appearance of GA shows there is a superficial perivascular lymphocytic infiltrate. Mononuclear cells are present among collagen bundles in association with variable mucin deposition. In well developed lesions, there are zones of mucinous necrobiosis of collagen surrounded by mononuclear cells. One may also see multinucleated giant cells. Fully developed lesions and deep subcutaneous nodules demonstrate palisaded granulomatous dermatitis or a septal and lobular panniculitis respectively. A Guide To Differential Diagnosis For Granuloma Annulare    • Annular lichen planus    • Diabetic dermopathy    • Erythema annulare centrifugum    • Erythema elevatum diutinum    • Erythema migrans of Lyme disease    • Lichen planus    • Necrobiosis lipoidica diabeticorum    • Perforating collagenosis    • Rheumatoid nodules    • Sarcoidosis

Assessing The Treatment Options

   Treatment is not necessary in many cases because GA is self-limiting and usually asymptomatic. However, treatment may be warranted in those cases that occur with pruritus or spreading of the lesions, and in cases in which the patient is very concerned about the appearance of the condition.    For most localized cases, one can generally treat the condition successfully with topical corticosteroids. Clinicians may have the patient apply potent topical steroids such as clobetasol 0.05% (Temovate®) or desoximetasone 0.05% cream (Topicort®) twice a day. I tend to prefer using fluocinolone 0.025% cream (Synalar®) in most cases. One should instruct patients to use these products for up to two weeks without occlusion. Also be sure to caution them to not use these creams on their faces.    Another very successful topical treatment for GA is flurandrenolide adhesive tape (Cordran® Tape). This clear tape has the steroid impregnated into the adhesive and it gradually releases into the tissues once one applies it over an area of dermatoses. This provides occlusion and steroid therapy as well as protection from external irritation and scratching. Patients may have the tape on for eight to 12 hours a day and it can be worn at night while patients are sleeping.    When it comes to larger or more symptomatic lesions, one may employ intralesional injections of dexamethasone or betamethasone sodium phosphate. I have always used a mixture of local anesthetic agent and steroid in a 1:1 ratio for these injections. For even larger lesions and nodular GA, clinicians may use intralesional injections of triamcinolone (Aristocort®) 5 mg/mL. It is important to be aware that steroid injections have the potential for dermal atrophy and pigmentary changes.

What One Can Expect With The Prognosis Of GA

   The prognosis of localized GA is good with over half of all cases spontaneously resolving within two years although many lesions may last for several decades. Unfortunately, approximately 40 percent of cases recur, usually at the same location as the original lesion. However, most recurrent lesions are smaller and may resolve quickly with therapy. The subcutaneous and nodular types of GA may also spontaneously remiss but to a lesser degree. These lesions are also relatively responsive to steroid injection therapy.    Generalized GA and perforating GA, in contrast, have a more chronic course with little reported spontaneous resolution. They are also poorly responsive to most therapy and have a higher recurrence rate.

What One Retrospective Study Of Granuloma Annulare Revealed

   A retrospective study was performed on 29 patients with granuloma annulare who presented at the Seattle Foot and Ankle Clinic from 1986 through 1998. Documentation at the time of the first visit included the patient’s age, sex, location of skin lesion(s), the type of GA present, duration of lesion(s) and the association of other disease states (see “What One Retrospective Study Of Granuloma Annulare Revealed” below). We also took photographs of all clinical lesions at the initial presentation.    While there was no predilection for any particular racial type, there were a large number of fair complexioned females in this study. The average follow-up was 12 months. During the follow-up, no patients developed signs or symptoms of rheumatologic disease or atopic dermatitis.    There were 20 females and nine males in the study and they ranged from 4 to 35 years of age. There were 12 cases of subcutaneous GA (41 percent), seven cases of localized GA (24 percent), six cases of nodular GA (21 percent), two cases of generalized GA (7 percent) and two cases of perforating GA (7 percent). Patients reported very few symptoms although 10 patients (35 percent) did complain of mild to moderate pruritus or irritation of the lesion with shoe gear.    As one can see from the table of data, there is some overlap of the sites of lesion occurrence. Seventeen patients (59 percent) had pretibial GA lesions, 14 patients (48 percent) had foot and ankle lesions, and 12 patients (41 percent) had hand lesions. The two oldest patients in the study (a 31-year-old male and 35-year-old female) both had the perforating type of GA and both had insulin-dependent diabetes mellitus.    Additional findings showed there were 10 patients (35 percent), representing nine females and one male, who were 10 or younger. There were also 16 patients (55 percent), representing eight females and eight males, who were 15 or older. There were only three patients (1 percent) who were 30 or older. The left extremity was involved in 19 patients, the right extremity in seven patients and both extremities in three patients.    We confirmed the diagnosis pathologically by biopsy specimen for 23 patients (79 percent) and clinically in the remaining six patients (five of whom were 8 years of age or younger). The majority of biopsies were of the 4 mm punch type (17 patients or 74 percent of the biopsies) and the others were all of the incisional biopsy type (six patients or 26 percent of the biopsies). For four patients, the lesions resolved soon after we obtained the biopsy and none of these cases were treated.    When given a choice between treatment and no treatment, the majority of patients chose the treatment option. We provided treatment for 20 patients (69 percent) and the remaining nine patients (including the four who had resolved conditions after the biopsy) received only advice and follow-up examinations. It is interesting to note that all but one of the non-treated cases was under the age of 10.    For most cases of localized GA, we treated patients with topical fluocinolone 0.025% cream (Synalar®) if the lesions were greater than 3 cm in diameter or flurandrenolide 4 mcg/cm2 adhesive tape (Cordran® Tape) if the lesions were less than 3 cm in diameter. We treated most of the subcutaneous GA cases with intralesional injections of 0.5% bupivacaine and dexamethasone sodium phosphate 4 mg/mL mixed in equal parts. For patients who had nodular GA, we employed intralesional injections of 0.5% bupivacaine and triamcinolone 5 mg/mL in equal parts. We treated the two cases of perforating GA and one case of generalized GA with a combination of topical and injectional therapies. In all of the cases we treated, there was significant improvement or resolution of clinical appearance and/or symptoms within three weeks of starting therapy.

Case Study: A 16-Year-Old With Pruritic Dermatitis For One Month

   A 16-year-old female presented with a complaint of pruritic dermatitis on the left foot of one month duration. The only positive history was for birth control pills, which she had started taking three weeks prior to noticing the skin condition.    This lesion was in an annular pattern on the dorsum of the foot and lateral ankle region. The lesion had slightly elevated peripheral borders with palpable and mobile subcutaneous granules. Further examination revealed a much smaller but similar lesion on the top of the right hand. We recommended a biopsy but the patient declined. We made a clinical diagnosis of subcutaneous granuloma annulare based upon the appearance, location and presenting findings in the case.    We began treating the foot lesion with an intralesional injection of equal parts of 0.5% bupivacaine and dexamethasone sodium phosphate. The patient subsequently received a prescription for a 15-gm tube of fluocinolone 0.025% cream with instructions to apply the cream twice a day to all lesions.    In two weeks, the patient had approximately 80 percent clearing of the lesions on the foot. At a four-week follow-up, there were no signs of the lesions present. We did tell the patient about the possibility of recurrence and instructed her to return if the lesions came back.

In Conclusion

   Granuloma annulare is a benign inflammatory skin condition that occurs most frequently in the lower extremities (anterior pretibial and foot region) among young patients, predominantly in females. The incidence of spontaneous remission is high with the localized type of GA and there is an elevated incidence of recurrence and formation of multiple lesions. While a biopsy is required for definitive diagnosis, it is not always necessary, especially when it comes to cases of recurrent lesions with a previous biopsy and when assessing young children. One should advise the patient and family as to the benign and noninfectious nature of the skin condition as well as the recurrent nature of the lesions. Dr. Dockery is a Fellow of the American College of Foot and Ankle Surgeons, the American College of Foot and Ankle Pediatrics and the American Society of Podiatric Dermatology. He is the Chairman of the Board and Director of Scientific Affairs at the Northwest Podiatric Foundation for Education and Research, USA in Seattle.



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