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Disease Profile

Granuloma annulare

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

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ICD-10

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Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Categories

Skin Diseases

Summary

Granuloma annulare (GA) is skin disorder that most often causes a rash with red bumps (erythematous papules) arranged in a circle or ring pattern (annular).[1][2][3] GA is not contagious and is not cancerous.[2] The rash may be localized or generalized. Localized GA is the most common form of GA (75% of the cases) and usually affects the forearms, hands, or feet. The generalized form of GA (15% of cases) presents with numerous erythematous papules that form larger, slightly raised patches (plaques) anywhere on the body, including the palms of hands and soles of feet. The plaques may or may not be in the ring pattern and can vary in color. Less common forms of GA include subcutaneous, perforating, and patch variants.[2][3][4][5] 

The underlying cause of GA is unknown, but there are several factors that may trigger the disorder, including injury to the skin, viral infections, and certain medications and medical diseases. However, most cases of GA develop in healthy people.[1][2][3][4][6] Some researchers propose unknown genetic factors may increase a person's risk to develop GA.[3][5] Diagnosis of GA is made by the appearance of skin lesions and lack of other physical findings or symptoms. GA may be confirmed by a biopsy and tests may be performed to rule out other associated diseases.[1][3] GA usually goes away without treatment within a few weeks to several years. However GA can sometimes last for decades, especially the generalized form. Steroids creams or injections and other therapies may be used to clear the rash more quickly, but are not successful in all cases, especially for those with the generalized form. Even after GA completely goes away, it may develop again.[1][3][4][6]

Symptoms

Signs of granuloma annulare (GA) vary depending on the specific form:[1][2][3][4][5]

  • Localized GA presents with small, skin-colored or reddish firm bumps (erythematous papules) on the back of arms, wrists, ankles, hands, and feet. The bumps are usually, but not always, arranged in a circular or ring pattern. Involvement of the palms of the hands, face, scalp, and genitals is rare. Lesions of localized GA typically grow slowly, and in about 50% of the cases there is more than one lesion.
  • Generalized GA may present as widespread bumps (papules), multiple ring shaped, raised patches (plaques), and/or large discolored, oddly shaped plaques. The color of the papules and plaques may be skin color, yellow, reddish pink, or violet and may cause itching.[3] The sizes of the plaques may range from millimeters to several centimeters in diameter. The lesions of generalized GA can form anywhere on the body, but are most common on the trunk, arms, and legs. Generalized GA can affect the neck, face, scalp, soles of feet, and palms of hands.
  • Subcutaneous GA presents with painless, round, firm lumps (nodules) that develop under the skin on the knees, ankles, feet, hands, scalp, eyelids, and/or buttocks. There can be one lump or a cluster of lumps. The lumps are usually less than 4 cm in size. The skin over the lumps may be skin colored, pink, or red, but otherwise normal in appearance. In some cases, the lumps of subcutaneous GA may grow quickly. 
  • Perforating GA presents with small bumps with crusted centers (umbilicated papules) that may leak fluid, itch, and be painful. The bumps may feel scaly and become filled with pus or ulcerate. This rare form usually affects the hands and fingers. However perforated GA may develop anywhere on the body, especially in scars. A person may have a few bumps or many bumps that join together to form raised patches of skin (plaques). This is the only type of GA that usually leaves scars when it heals.
  • Patch GA presents with patch-like lesions that may be localized or generalized and are most commonly located in the legs or arms. The patches may be red, reddish brown, or violet.

Children tend to get the localized and subcutaneous types of granuloma annulare. The generalized and perforating types are more common in older adults.[1][2]

In addition to the above forms, GA has been reported to occur in a linear pattern or as very painful papules or plaques.[3]

Cause

The cause of granuloma annulare (GA) is unknown but many researchers have proposed it may involve an immune and/or inflammatory response.[3][4][6] While most cases occur in people who are otherwise healthy, there are a number of triggers and associated diseases. It has been reported to follow insect bites, sun exposure, tuberculin skin tests, tattoos, other injuries to the skin, certain medications (allopurinol, diclofenac, quinidine, calcitonin, amlodipine, ACE inhibitors, daclizumab, and calcium channel blockers), and viral infections (including Epstein-Barrhepatitis C, herpes zoster, and HIV). GA has been associated with the development of other medical conditions including autoimmune thyroiditis, diabetesdyslipidemia, and cancer.[1][3][4][5] Chronic stress may be another trigger.[1] However, researchers do not understand why GA only develops in a few people who are exposed to any of these triggers. Although a genetic predisposition to develop GA has been proposed, no specific genetic change (variant) has been found.[1][3][5]

Since there are many different triggers and possible associated diseases, as well as different forms of GA, some researchers suggest that there is no single cause of GA, but rather multiple pathways that when triggered can lead to the development of this skin disorder.[6] 

Treatment

If granuloma annulare (GA) does not cause bothersome symptoms like itching, then it usually does not need to be treated.[3][7] If GA does cause symptoms, it can be difficult to find the best treatment, because treatment options for GA have not been studied in large clinical trials. Information about treatment options is available only through published reports from individual cases, a small number of cases, or small uncontrolled studies.[3][4]

The localized form of GA may be treated with topical steroid creams, topical tacrolimus or pimecrolimus, freezing the lesions (cryotherapy), or laser therapy. Injecting triamcinolone acetonide, a type of steroid, into lesions has also been successful in some cases. In general, steroid creams are usually tried first.[3][4][7]

The generalized form of granuloma annulare can be more difficult to treat and many treatment options have been tried. Again, the first treatment is usually topical steroid cream or steroid injections into the lesions. These treatments work best before the lesions are very widespread. Predinsone taken orally (systemic steroid treatment) may also be effective early in the treatment of generalized GA, but the lesions may return when the steroid treatment is stopped. Light therapy, also called phototherapy, is the next main treatment option and involves exposing the skin to ultraviolet light. Light therapy options may include UVA1 phototherapyPUVA photochemotherapy, or photodynamic therapy.[3][4]

Other medications that may be given for generalized granuloma annulare include hydroxychloroquine, isotretinoin, or dapsone. Combinations of certain antibiotics (rifampin, ofloxacin, and minocycline) have been shown to be successful in some cases. For people with very severe disease, treatment options may include cyclosporineinfliximab, or adalimumab.[3][4][7] In Europe where fumeric ester acids (FEA) have been approved for the treatment of severe psoriasis, FEA has been reported to be effective in treating some cases of generalized GA.[4]

Many of these treatments have shown results in only a few patients and can have side effects. The risks and benefits of each treatment option should be discussed with your doctor.[3][4]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Social Networking Websites

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • DermNet New Zealand is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated. DermNet NZ provides information about this condition.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Granuloma annulare. Click on the link to view a sample search on this topic.

References

  1. Ghadially R. Granuloma Annulare. MedScape Reference. October 29, 2018; https://emedicine.medscape.com/article/1123031-overview.
  2. Granuloma annulare. American Academy of Dermatology. February 8, 2018; https://www.aad.org/public/diseases/rashes/granuloma-annulare#overview.
  3. Brodell RT. Granuloma annulare. UpToDate. January 3, 2020; https://www.uptodate.com/contents/granuloma-annulare.
  4. Wang J, Khachemoune A. Granuloma Annulare: A Focused Review of Therapeutic Options. Am J Clin Dermatol. June 2018; 19(3):333-344. https://www.ncbi.nlm.nih.gov/pubmed/29230666.
  5. Piette EW, Rosenbach M. Granuloma annulare: Clinical and histologic variants, epidemiology, and genetics. J Am Acad Dermatol. September 2016; 75(3):457-465. https://www.ncbi.nlm.nih.gov/pubmed/27543209.
  6. Piette EW, Rosenbach M. Granuloma annulare: Pathogenesis, disease associations and triggers, and therapeutic options. J Am Acad Dermatol. September 2016; 75(3):467-479. https://www.ncbi.nlm.nih.gov/pubmed/27543210.
  7. Oakley A. Granuloma annulare. DermNet New Zealand. October 2015; https://www.dermnetnz.org/topics/granuloma-annulare.

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