Granuloma annulare (GA) is a common, sometimes chronic

skin condition A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this s ...

which presents as reddish bumps on the

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different de ...

arranged in a circle or ring. It can initially occur at any age, though two-thirds of patients are under 30 years old, and it is seen most often in children and young adults. Females are two times as likely to have it than males.

Signs and symptoms

Aside from the visible

rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, c ...

, granuloma annulare is usually asymptomatic. Sometimes the rash may burn or itch. People with GA usually notice a ring of small, firm bumps (papules) over the backs of the forearms, hands or feet, often centered on joints or knuckles. The bumps are caused by the clustering of

T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...

s below the skin. These papules start as very small, pimple looking bumps, which spread over time from that size to dime, quarter, half-dollar size and beyond. Occasionally, multiple rings may join into one. Rarely, GA may appear as a firm nodule under the skin of the arms or legs. It also occurs on the sides and circumferential at the waist and without therapy can continue to be present for many years. Outbreaks continue to develop at the edges of the aging rings.

Causes

The condition is usually seen in otherwise healthy people. Occasionally, it may be associated with

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

thyroid disease Thyroid disease is a medical condition that affects the function of the thyroid gland. The thyroid gland is located at the front of the neck and produces thyroid hormones that travel through the blood to help regulate many other organs, meaning ...

. It has also been associated with auto-immune diseases such as systemic lupus erythematosus,

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are invol ...

Lyme disease Lyme disease, also known as Lyme borreliosis, is a vector-borne disease caused by the ''Borrelia'' bacterium, which is spread by ticks in the genus ''Ixodes''. The most common sign of infection is an expanding red rash, known as erythema migran ...

and

Addison's disease Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adre ...

. At this time, no conclusive connection has been made between patients.

Pathology

Granuloma annulare microscopically consists of

dermal The dermis or corium is a layer of skin between the epidermis (with which it makes up the cutis) and subcutaneous tissues, that primarily consists of dense irregular connective tissue and cushions the body from stress and strain. It is divided ...

epithelioid histiocytes around a central zone of mucin—a so-called palisaded granuloma.

Pathogenesis

Granuloma annulare is an idiopathic condition, though many catalysts have been proposed. Among these is

skin trauma Skin trauma is serious and altering physical injury experienced by the skin or multiple layers of epithelial tissue Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue ...

, UV exposure,

vaccination Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...

tuberculin skin test The Mantoux test or Mendel–Mantoux test (also known as the Mantoux screening test, tuberculin sensitivity test, Pirquet test, or PPD test for purified protein derivative) is a tool for screening for tuberculosis (TB) and for tuberculosis diagn ...

ing, and ''

Borrelia ''Borrelia'' is a genus of bacteria of the spirochete phylum. Several species cause Lyme disease, also called Lyme borreliosis, a zoonotic, vector-borne disease transmitted by ticks. Other species of ''Borrelia'' cause relapsing fever, and are t ...

'' and

viral infection A viral disease (or viral infection) occurs when an organism's body is invaded by pathogenic viruses, and infectious virus particles (virions) attach to and enter susceptible cells. Structural Characteristics Basic structural characteristics, ...

s. The mechanisms proposed at a molecular level vary even more. In 1977, Dahl et al. proposed that since the lesions of GA often display a thickening of, occlusion of, or other trauma to

blood vessel The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away ...

s, blood vessels may be responsible for GA. From their study of 58 patients, they found that immunoglobin M (IgM),

complement A complement is something that completes something else. Complement may refer specifically to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-clas ...

, and

fibrinogen Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood cl ...

were in the blood vessels of GA areas, suggesting that GA may share similarities with an

immune-mediated An immune disorder is a dysfunction of the immune system. These disorders can be characterized in several different ways: * By the component(s) of the immune system affected * By whether the immune system is overactive or underactive * By whether ...

, type 3 reaction or that chronic immune

vasculitis Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily caused ...

may be involved in the

pathogenesis Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...

. Another study found evidence suggesting blood vessel involvement with masses of intercellular fibrin and thickened basal lamina found around capillaries. Umbert et al. (1976), proposed an alternative pathogenesis: cell-mediated immunity. Their data suggests that

lymphokine Lymphokines are a subset of cytokines that are produced by a type of immune cell known as a lymphocyte. They are protein mediators typically produced by T cells to direct the immune system response by signaling between its cells. Lymphokines have ...

s, such as macrophage-inhibiting factor (MIF), leads to sequestration of macrophages and

histiocyte A histiocyte is a vertebrate cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyt ...

s in the dermis. Then, upon lysosomal enzyme release by these sequestered cells, connective tissue damage ensues, which results in GA. Later, these authors found data suggesting that activation of macrophages and fibroblasts are involved in the pathogenesis of GA and that fibrin and the rare IgM and C3 deposition around vessels were more likely a delayed-type hypersensitivity with resulting tissue and vessel changes rather than an immune-complex mediated disease. Further data has been collected supporting this finding.

Diagnosis

Types

Granuloma annulare may be divided into the following types: :* Localized granuloma annulare :*

Generalized granuloma annulare Generalized granuloma annulare is a skin condition of unknown cause, tending to affect women in the fifth and sixth decades, presenting as a diffuse but symmetrical, papular or annular eruption of more than ten skin lesions, and often hundreds. ...

:* Patch-type granuloma annulare :* Subcutaneous granuloma annulare :* Perforating granuloma annulare

Treatment

Because granuloma annulare is usually asymptomatic and self-limiting with a course of about 2 years, initial treatment is generally

topical steroid Topical steroids are the topical forms of corticosteroids. Topical steroids are the most commonly prescribed topical medications for the treatment of rash, eczema, and dermatitis. Topical steroids have anti-inflammatory properties and are classifie ...

s or

calcineurin inhibitors Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified into ...

; if unimproved with topical treatments, it may be treated with intradermal injections of steroids. If local treatment fails it may be treated with systemic corticosteroids. Treatment success varies widely, with most patients finding only brief success with the above-mentioned treatments. Most lesions of granuloma annulare disappear in pre-pubertal patients with no treatment within two years while older patients (50+) have rings for upwards of 20 years. The appearance of new rings years later is not uncommon.

History

The disease was first described in 1895 by Thomas Colcott Fox as a "ringed eruption of the fingers", and it was named ''granuloma annulare'' by Henry Radcliffe Crocker in 1902.

References

External links

* {{Cutaneous ketatosis, ulcer, atrophy, necrobiosis, and vasculitis Monocyte- and macrophage-related cutaneous conditions Ailments of unknown cause Rare diseases