Granuloma Annulare and Necrobiosis Lipoidica

Granuloma annulare (GA) is a skin disease commonly encountered in our clinic, either as an initial self-motivated visit or on consultation from another physician. The rash consists of small smooth bumps that may be skin-colored, pink, reddish-purple, brownish-orange. The bumps may coalesce into rings with clearing in the center; that is what the descriptive annulare implies. The word granuloma refers to a type of chronic inflammation in the dermis (second layer of skin) consisting of lymphocytes and histiocytes that  alters the microscopic appearance of the connective tissue.

Patients who have GA are generally aware of their rash because they can see it on their skin, but it usually doesn’t cause symptoms in localized cases. I will occasionally find previously unsuspected areas of localized GA lesions on patients during a routine skin examination. Some patients experience a more generalized form of GA and complain of a tingling or burning type of sensation in the skin. While most granulomas are superficial, it is possible to have deeper subcutaneous nodules of GA, and these may be painful if they are located on pressure-bearing points such as the elbows, knees, or hands.

GA can occur anywhere on the body skin, but it is most commonly seen on the upper and lower extremities, especially hands, feet, wrists and ankles. Face and neck involvement is uncommon. The cause is not known. An association with diabetes mellitus has been considered for decades but never proven conclusively. Dermatologists used to order fasting blood sugar tests on patients with new-onset GA, but that is rarely done now. GA occurs in children and adults. I have noticed that children’s GA rash tends to be the annular or ring-shaped type localized to hands and feet that often resolves spontaneously over time, sometimes years. The adult type of GA tends to be more widespread and may consist of individual bumps that coalesce into larger plaques. Some of these have a tendency to show central clearing. Other bumps join to form rings, partial rings, or arcs. I believe the more generalized cases of GA are much less likely to clear spontaneously and are more resistant to medical treatments.

How is the diagnosis of GA made? In children, the skin lesions are usually so typical for GA, that the diagnosis can be made by a Dermatologist on clinical grounds alone. A Pediatrician may consider that the ring of GA resembles “ringworm” or fungal infection, but the latter lesion is redder and more scaly than GA. In adults, although the rash may be recognizable, it is desirable to confirm the diagnosis by taking a skin biopsy because there are a few other diseases that resemble GA. One of these is sarcoidosis. Sarcoidosis is a multi-system disease of unknown cause marked by granulomatous inflammation of skin, eyes, lungs, liver, spleen, bone, and other internal organs. Biopsies of involved skin show deeper and more organized granulomas. Where subcutaneous GA is suspected, in the proper setting, rheumatoid nodules must also be considered.

Necrobiosis lipoidica

Another possibility when considering GA is necrobiosis lipoidica.

Necrobiosis lesions are generally found on the shins, have an  association with diabetes, and resemble GA lesions except for thin yellowed waxy skin in the center of a plaque with capillaries visible on the surface. While the cause of Necrobiosis lipoidica is not known, the current accepted theory is that oxygen delivery to the affected skin is compromised by deposits of glycoprotein leading to thickening of blood vessel walls. The association of Necrobiosis lipoidica with diabetes may also have been exaggerated. A recent review article (November 2013 Journal of the American Academy of Dermatology) stated that the incidence of necrobiosis in diabetics is only 0.3% to 1.2%. Moreover, in patients who have both, Necrobiosis preceded the diagnosis of diabetes in about 14%, occurred simultaneously in 24%, and followed the diagnosis of diabetes in 62%. About half the cases of coexisting Necrobiosis and diabetes become insulin-dependent.

I have seen several cases where GA lesions actually coexisted along side Necrobiosis lesions, leading some investigators to speculate that GA is caused by damage to small blood vessels called “microangiopathy” similar to that observed in Necrobiosis associated with diabetes.

Treatment of Granuloma Annulare

Note the similarity between Rheumatoid nodules of the fingers and subcutaneous GA.

How is GA treated? Curiously, a localized lesion of GA may actually resolve after a skin biopsy without active treatment. We call this a “therapeutic biopsy.” (I have also observed this phenomenon after a biopsy of a large resistant plaque of psoriasis.)  More often, a corticosteroid in the form of a cream, ointment, impregnated occlusive tape (Cordran), or locally injected dilute suspension (Kenalog) is effective, at least in the short-term. In more disseminated or generalized cases, intramuscular Kenalog or oral prednisone tablets give at least temporary improvement. Phototherapy, that is, ultraviolet light, narrow band UVB or PUVA, is also effective in some cases. For the most resistant cases, anti-inflammatory drugs such as plaquenil, dapsone, and pentoxyphylline may be prescribed for a trial of therapy.

A November 2012 case was reported in Clinical and Aesthetic Dermatology where a 73-year-old woman with generalized GA for 40 years was treated with the excimer laser.  She had complete clearing after 15 exposures with this laser which generates a potent, highly focussed beam of narrow band UVB.  To my knowledge, this was the first report of excimer laser used for GA, and I look forward to trying this modality on my patients who have failed to respond to conventional therapies.

What’s New?

An important paper in my opinion was published in the October 2012 issue of the Archives of Dermatology. In this article, the authors showed that 140 patients with GA had a startlingly high prevalence of abnormal fasting blood lipids (79%) compared to 420 matched case control subjects without GA (52%). Moreover, patients with generalized GA were even more likely to have abnormal lipids than other GA types. After controlling for all other risk factors, it was 4 times more likely to find abnormal lipids in GA patients than in control patients without GA.  The authors and the accompanying editorial suggested that we should screen for fasting levels of cholesterol, triglycerides, HDL-C, and LDL-C in patients with GA. The finding of previously unknown lipid abnormalities may suggest the need for lipid-lowering agents in these patients as well as other lifestyle changes intended to reduce risk to the cardiovascular system.

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