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.

More About Autoimmune Diseases:
When Should a Primary Care Doc Refer to a Dermatologist?
REM Syndrome

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40 Responses to Granuloma Annulare and Necrobiosis Lipoidica

  1. Pingback: Rings on the Palms and Scales on the Soles |

  2. April says:

    Thank you for the information and pictures. I finally figured out what the ring shaped (almost identical to the one pictured on the website) was… I developed it after I received a “rug burn” on the hospital bed during labor/delivery. It has been two years and is less prevalent and rarely itches. I have just developed a cluster on my back however, which I will seek treatment for. Starts out flesh/purple, then fades to skin colored over the next several months. I have history of Colitis, Celiac, Seasonal Allergies.

  3. Barbara Cott says:

    Would love to know if anything new is discovered about this condition

  4. Amy says:

    I am a 49 year old woman with generalized GA on my torso. I had GA as a child (ankle) which spontaneously resolved. Then generalized onset at 30 which completely cleared when pregnant. After pregnancy, the GA returned and has never resolved.

    Cordran tape gives temporary relief, but the GA returns in the same spots. What treatment do you recommend? My dermatologist is hesitant to treat aggressively as I do not have itching/bothersome symptoms beyond the appearance.

    • DrCamisa says:

      Generalized GA is just very difficult to treat for the reasons you gave. My favorite choices for more aggressive therapy would be plaquenil and PUVA.

  5. Janell oberle says:

    I am 38 years old have type 1 diabetes and have severe granuloma annulare on my legs and are, few spots on my torso. I have been to 3 dermatologist with no seccess. Have been trying some natural things like apple cider vinager, black cumin seed, and was thinking about trying the curcumin. What would be your thoughts on it helping

    • DrCamisa says:

      Curcumin has potent anti-oxidant and anti-inflammatory effects. Since granuloma annulare is a chronic inflammation of the skin, curcumin might have a beneficial effect on it. I think it would be worth trying. I like the new bio-curcumin product from Life Extension.

  6. Travis Novak says:

    I had been suffering with what I thought was ringworm for almost a year. My doctor finally sent me to a dermatologist where I was diagnosed as having GA. I am a 42 year old male and am having a difficult time. I have the rings on my upper chest, elbows, knees, thighs and ankles. Psychologically it is taking a toll on me. I feel like other people are looking at me like I have some contagious disease. I am an active outdoor person but because of this I will not take my shirt off not where shorts. My dermatologist says there is nothing that can be done. Over the last year the rings have become larger and I am at a loss having used steroid creams already with no success. I almost don’t want to go out in public at all. I would really like to know if anything has worked for anyone else.

    • DrCamisa says:

      In addition to topical steroids, shots of cortisone injected directly into lesions, and steroids given internally by pills or intramuscular injection all work for GA temporarily but may have significant side effects. As I said earlier, there are no great treatments for widespread GA, but the safest treatments currently are plaquenil and ultraviolet light A, in my opinion.

  7. Linda says:

    I have what looks to be this rash and have had it off and on for years. Recently I discovered by accident that each time I take zinc it gets better. So then I got myself some sunscreen with a high amount of zinc, and lo and behold, it’s clearing up after 2 applications.

    • DrCamisa says:

      What a great observation! I recommend small amounts of zinc supplementation such as 30-50 mg per day to support the immune system and promote healing. Thus, it is possible that external zinc oxide in sunscreen would help as well. I’m going to give it a try.

  8. Susan Bottwood says:

    I have been diagnosed with GA after a temporary change in lifestyle that means I no longer visit the south of France where I was in the habit of using sunscreen on a daily basis and spending time in a climate with lots of sun and light.
    On my return to the UK I began to notice lesions on my knees, elbows and truck. After almost a year of no sun, no sunscreen I have a regular occurrence of additional lesions. I have been using prescribed cortisone cream for four months but with only minor noticeable improvement and new lesions continue to appear.
    I am thinking of trialling daily use of sunscreen (Lancaster Factor15) despite it being cold and grey here in London. Not sure what the zinc content of the sunscreen is, but intend to find out. What do you think?

    • DrCamisa says:

      I’m thinking that it was the sunlight exposure that was helping the Granuloma Annulare (GA). We use both Ultraviolet-B and Ultraviolet-A light to treat generalized GA in our phototherapy cabinets. Zinc oxide is present in many sunscreens in various concentrations, but I think it is inert with the skin and only blocks all UV rays and also water contact with skin. We use it to treat napkin dermatitis. If you want to take biologically active zinc that benefits the immune system, take a low dose of a supplement, such as 50 mg once daily.

  9. Sandra Balkin says:

    I have GA on the top of my foot. Quite often the top of my foot hurts. Could this be from the GA? It has been there for a year and a half and appears to be getting larger. I used steroid cream, but it did not help. My sister cannot eat gluten. Do you think that could be the problem?

    • DrCamisa says:

      Granuloma Annuare (GA) usually does not cause pain. Steroid creams don’t always help GA. Sometimes it’s necessary to apply an steroid-impregnated tape (Cordran) or receive injections of the steroid right into the skin lesions. Ask your Dermatologist about those treatments. As for the gluten question, please see my article on this blog. To my knowledge, gluten intolerance is not associated with GA, but it wouldn’t hurt to try your sister’s diet for a month or so. Thanks for your intuitive questions that are helpful to our other readers.

  10. Carolyn I says:

    Thank you for the article on Granuloma Annulare. I have this and didn’t connect the new lumps on my knuckles until reading this article and seeing the pictures. It appears my hands are just starting with these lumps, but they are causing some pain. As these lumps get bigger, will removing them be an option since they are so unsightly? I have found that the bumps on my arms and legs and once on my torso go away on their own, except for the one that was biopsied and found out what it was. Also, the lumps on my knuckles are harder than the other ones on my body. Are they the same material inside?

    • DrCamisa says:

      Some people who have Granuloma Annulare (GA) all over their body may also develop deeper firmer nodules of GA on their hands, fingers, elbows and knees. The “material” in the nodules is the same as in the thinner softer lesions on the body, only deeper and more of it. That material is actually the infiltration of inflammatory cells around collagen bundles and the accumulation of a polysaccharide called mucin. I have found that subcutaneous GA usually responds well to local injections of a triamcinolone solution.

  11. Lt says:

    Thank you for your work and interest in this terrible condition. I am wondering if most people with the generalized form typically get the nodules on hands and knuckles. This disease is so horrible.
    Please tell me if you are aware of success with ROM therapy once a month. Rifampin, oxyfloxacin, minocycline? I saw two articles that mentioned success , but study was limited to just a few individuals.

    • DrCamisa says:

      Nodules on the hands and knuckles are fairly common in the generalized form of granuloma annulare. I have not heard of “ROM” therapy. I probably wouldn’t recommend it because I don’t see a role for antibiotics in this disease

  12. Lee says:

    I’ve had GA for about four years with it first appearing on the back of one hand. Now I have it on both hands, an elbow, back of the neck and a leg. I had a biopsy to confirm what it was and use a steroid cream but my doctor said not to use it daily because it will thin the skin, plus other side effects and it really doesn’t seem to be doing any good. Thank you for the information you’ve provided. I am going to try adding zinc to my diet. Also, I did read that in rare cases Amlodipine seems to have caused GA in some people. Since I do take this I’m going to ask my doctor for an alternative and see what happens. The GA appeared about three months after starting it. Have you had any experience related to Amlodipine?

    • DrCamisa says:

      Thank you for question. I have many patients who take amlodipine for high blood pressure, and it’s a good drug. I haven’t seen any patients who developed GA after taking amlodipine. However, anything is possible, so if your doctor thinks it’s safe to stop amlodipine, then you should do that for at least one month to see if it makes a difference in the GA. The doctor may want to substitute a different medicine to control your blood pressure while you’re off amlodipine. Good luck.

  13. e. beaven says:

    I have generalized granuloma annulare for 30 years. Google: generalized granuloma annulare and ROM therapy. New treatment being explored and sounds good. Henry Ford Health System and India study with good results. Am going to discuss with my Dermatologist on next visit. Good luck to us all.

  14. KS says:

    I have been diagnosed w/ GA.All of the spots are splotchy areas and circular in nature. I had a biopsy of one of the spots on my leg.The dr suggested a steroid cream, but I did not use it. I chose instead to take all gluten out of my diet.These areas slowly began to fade. At times when I have found I was eating “hidden” gluten, a spot or two would come back.Again, when I would discover the gluten and remove it, the spot(s) would begin to disappear.

    • DrCamisa says:

      Granuloma annulare is not considered to be a skin disease that is caused or aggravated by the ingestion of the wheat protein called gluten. However, the cause of GA is not known. Therefore, it is possible that some cases like yours may be sensitive to gluten. Following a strict gluten-free diet is difficult, but it is safe. A trial of a gluten-free diet for a month or more may be a reasonable approach for GA-sufferers.

      • S.R. says:

        I was diagnosed 16 years ago with this on my toes, About 2 years ago it became obvious on my knuckles, I went for another biopsy about a month ago, and the dr. suggested trying Niacinamide (a non-flush version of niacin), I take 2 pills daily of 500mg. each (without insurance…the cost is under $3.00 a month) and so far… 1 month later the hand nodules have receded about 85%! I also take fish oil and a multivitamin daily.

  15. CDG says:

    i have had generalized GA for about 4 years. Narrow band UVB phototherapy helped but was only a temporary fix. After a year I was tired of the 3 time a week treatments and the lesions returned. I was put on pentoxyphilline(Trental) 3times a day and the results are remarkable. Within 3 months the lesions faded and I have been on it now for 2years with no side effects. I tried a trial on 2x a day but after 2 months had a breakout of new lesions.

    • DrCamisa says:

      There have been numerous case reports of Trental helping GA, but it has never been proven effective in a double-blind trial. I have used it in a number of GA and Necrobiosis cases with limited effectiveness.

  16. Robert says:

    I am 65 year old male and have been afflicted with GA for roughly 5 years. I have tried cortisone creams and they are ineffective, was wondering since the last post if you have any more information regarding ROM treatment or laser treatment. In reading the previous posts they seem the most promising.

    • DrCamisa says:

      For those who haven’t been following this blog, ROM refers to 3 different antibiotics, Rifampin, Ofloxacin, Minocycline administered monthly. There was a recent report (2015) of 6 cases (5 generalized) that responded to it. I haven’t prescribed ROM yet because there haven’t been any placebo-controlled studies, but I may soon because it seems pretty safe.

  17. Emma McManus says:

    Hello everyone. I’m a 29 year old female from Ireland. I’ve been diagnosed with GA and have 3 lesions. The largest on the back of my calf which has been there for 2 years, the next on my ankle for about 6 months and a tiny one on my elbow just in the past week.
    I’ve been told it’s localised but I’m terrified of it spreading all over my body. Is it possible for the locAlised version to become generalised over time??
    I’m so frustrated that the knowledge and treatment for this condition is so poor. I know it may not be life threatening but it’s life altering and it has me mentally, emotionally drained.

    • DrCamisa says:

      It’s hard to predict whether localized GA will become generalized in an adult. In your relatively stable case, it’s probably unlikely to generalize. In similar cases, I have given intralesional injections of a corticosteroid suspension such as triamcinolone.

  18. Suzanne McDonald says:

    Interesting. It sounds like it is resistant to all kinds of medications and treatments, and chronic. In that respect it compares to MRSA/ORSA Skin Infection (MRSA has many different presentations over the body/skin) the common denominators with GA are it’s resistance, and seems to be responding to the same antibiotics: ROM). At the jails where I used to work for almost 10 years, many of the inmates would come in contact with MRSA (methicillin resistant staph aureus). Our protocol at the time was to take cultures and treat aggressively with two types of antibiotic therapy; we could choose from, 1: Bactrim DS w/Rifampin, or 2: Doxycycline w/Rifampin, or, 3: Clindamycin w/ Rifampin. Treating early was effective. Also together with wound care: cleansing w/ Normal Saline, or H2O2, applying Triple Antibiotic Ointment w/ an occlusive dry dressing x 14 days until healed, and repeat culture after treatment for test of cure. oh and contact isolation. If it recurred we’d culture the nares as it can colonize in the nostrils; and it will likely recur. We treated the nares w/ Bactroban 2% ointment, for 7days, if still recurs then we’d sometimes use Vyvox, or Dapsone.

    Skin infection is a very legitimate concern for all, as we know the skin is an important line of defense. We’ve even had to use iv Vancomycin. Also all linens and clothing were washed in hot water every day for 7 days, and disinfected all surfaces the patient could come in contact with everyday. This was done to prevent re-infection. Many of the inmate/patients were immunocompromised, (ie: hiv, liver disease, cirrhosis, pregnancy, etc) add stress, not much sunlight or exercise, not enough sleep as all the conditions in jail, on top of everything, including all their/patient’s comorbidities, it is no wonder how they may have become infected.

    Possibly intralesional injections of a corticosteroid together with ROM would increase treatment efficacy in GA. What do you think? ROM is relatively safe as long as the patient is not liver compromised, or have hiv infection due to the drug to drug interactions with many of the antiretroviral medications currently used for treatment of hiv, or the liver toxicity of mainly Rifampin.

  19. Nat says:

    My son is 7 and has had GA since he was 18 months. It started on his hands and then progressed to his feet. Cortisone cream helped a little as did oral doses of anti-inflamatory compounds like Vitamin E, Omega 3 and zinc. However recently he has taken to swimming and they do a lot of kick with flippers and this aggravates a large nodule on his foot. I would love to reduce this to a manageable size knowing currently a cure is out of the question.

    Surely with the knowledge gained over the past half decade there must be some theory as to what causes this unfortunate condition? Anti inflamatory substances seem to help and it seems some people respond well to a gluten free diet. UV treatment also has some effect as does antibiotic treatment – is this a clue as to what causes GA? Have any biopsies shown a viral infection? GA is a inflamatory condition and a lot of recent studies have shown a clear link between gut flora and many types of inflamatory responses. Surely someone somewhere is conducting research into this condition either by collating data and performing statistical analysis, or physiological testing of tissue and DNA.

    • Dr. Camisa says:

      The cause of GA is still a mystery. Perhaps a little intralesional injection of a cortsione solution will shrink the nodule. This type of localized GA in children has a very good chance of resolving on its own in time.

  20. David says:

    I occasionally get localized GA. Whenever it shows up, it will mirror on both sides of the body. It likes to show up on my inner arms near the armpit, and on my upper thighs and lower abdomen. There seems to be two different things that set it off. Intense heat…where I feel hot and sweaty and just cant seem to cool down…it will then show up a day or two later…and any intense nerve pain sometimes sets it off…

    Clobex helps a lot…but insurance doesnt cover the brand name…so the clobetasol SPRAY seems to help the most…typically goes away in about 5 days with the off brand…clobex used to do it in 2 or 3 days..

  21. Theresa Disney says:

    I was a 27 year old female when first diagnosed with GA. Now I am 61 years old. Over the years I’ve had every treatment I think possible. It used to be arms legs feet then legs. Now it is all over my body. I don’t know how much more I can take I don’t know where to go for help. Thx for listening. None of my family or friends understand.

  22. Mike Stiller says:

    I am a 52 year old male w/ no health issues, other than GA that started about 3 1/2 years ago, first noticed when I woke up one morning had a set of (small) GA rings on the back of my hand. I thought it was a bug bite…not so and not ring worm either. The GA rings now cover quite a bit of area on the back of my hands and some have appeared on my lower arms and neck. I also appear to have some subcutaneous GA on my arms as well. The dermatologist (in Akron, OH) I currently see has never seen a case of this in person and, aside from prescribing topical cortisone cream, has no great treatments to prescribe. After finding your blog, I’m certainly going to look into a number of the treatments suggested. Can you refer me to a different dermatologist in NE Ohio?

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