Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Granuloma Annulare Clinical Presentation

  • Author: Ruby Ghadially, MBChB, FRCP(C)Derm; Chief Editor: William D James, MD  more...
 
Updated: May 24, 2016
 

History

Both localized and generalized granuloma annulare lesions usually manifest as asymptomatic cutaneous lesions. Lesions may improve in winter and worsen in summer.

Subcutaneous granuloma annulare most often manifests as a large, asymptomatic soft tissue mass. Although nodules are usually stable for months, they may rapidly enlarge over the course of weeks.

Next

Physical

Patients with localized granuloma annulare commonly present with groups of 1- to 2-mm papules that range in color from flesh-toned to erythematous, often in an annular arrangement over distal extremities. Grouped lesions may expand into arciform or annular plaques measuring 1-5 cm in diameter. Centers of lesions may be slightly hyperpigmented and depressed relative to their borders, which may be solid or composed of numerous dermal papules. Lesions most commonly manifest on the dorsal surfaces of the feet, hands, and fingers, and on the extensor aspects of the arms and legs. Rarely, lesions appear on the face, scalp, or penis.

Patients with generalized granuloma annulare characteristically present with a few to thousands of 1- to 2-mm papules or nodules that range in color from flesh-toned to erythematous and involve multiple body regions. Lesions may coalesce into annular plaques, which measure 3-6 cm in diameter and which may enlarge centrifugally over weeks to months. Although any part of the cutaneous surface may be involved, lesions tend to be symmetrically disposed over acral areas and the trunk. Rarely, the head, palms, soles, and mucous membranes are involved.

Patients with subcutaneous granuloma annulare present with a firm, nontender, flesh-colored or pinkish nodule without overlying epidermal alteration. Lesions are typically solitary but may occur in clusters. The most commonly reported site of involvement is the lower extremities (65% of cases), often on the pretibial surface. Other typical sites include the fingers and palms and the dorsa of the feet. The buttocks, forehead, and scalp are less commonly affected. Deep dermal or subcutaneous nodules on the extremities are attached to fascia and are often therefore mobile, whereas lesions on the scalp are attached to underlying periosteum and are therefore fixed or only slightly mobile.

Patients with perforating granuloma annulare present with 1 to hundreds of grouped 1- to 4-mm papules that range in color from flesh-toned to erythematous. Papules often coalesce to form annular plaques. In some patients, the erythematous papules may evolve into yellowish pustular lesions that subsequently exude a thick and creamy or clear and viscous fluid, forming umbilicating, crusting, or scaling papular lesions that heal, leaving atrophic hypopigmented or hyperpigmented scars. Larger and more ulcerated plaques are common in middle-aged and elderly patients. Lesions affect all areas of the body but have a predilection for the extensor surfaces of extremities and the dorsa of hands and fingers.

Arcuate dermal erythema is an uncommon form of granuloma annulare that manifests as infiltrated erythematous patches that may form large, hyperpigmented rings with central clearing. Papules are a less prominent feature in this variant. Patches typically appear on the trunk and may spread centrifugally over weeks to months.

Patients with actinic annulare present with 1-10 plaques, which tend to be annular or serpiginous areas with raised erythematous borders. Lesions may be hypopigmented centrally; the epidermis is otherwise spared. Plaques are typically distributed over sun-exposed areas, such as the arms, neck, face, and dorsa of the hands. Other than by their location on heat- or sun-damaged skin, actinic annulare lesions are difficult to distinguish clinically from eruptions of granuloma annulare.

Previous
Next

Causes

The etiology of granuloma annulare is usually unknown, and the pathogenetic mechanisms are poorly understood, with a vast majority of granuloma annulare cases occurring in patients who are otherwise healthy. The range of predisposing events and associated diseases is diverse, and granuloma annulare is thought to represent a reaction pattern with many different initiating factors.

Granuloma annulare has been hypothesized to be associated with tuberculosis, insect bites, trauma, sun exposure, thyroiditis, vaccinations, and viral infections, including HIV, Epstein-Barr virus, hepatitis B virus, hepatitis C virus, and herpes zoster virus. However, these suggested etiologic factors remain unproven.

Familial cases of granuloma annulare observed in identical twins and siblings in several generations, along with an association of granuloma annulare with HLA phenotypes, suggest the possibility of a hereditary component in some cases. The HLA-B8 level has been reported to be increased in localized granuloma annulare; HLA-A29 and HLA-BW35 levels are reported to be increased in generalized granuloma annulare.

Some reports associate chronic stress with granuloma annulare as a trigger of the disease. Granuloma annulare also has some predilection for the sun-exposed areas and photodamaged skin. Photosensitive granuloma annulare has been found in association with HIV infection. Finally, some cases of granuloma annulare or granuloma annulare–like reactions have been reported after gold therapy and treatment with allopurinol, diclofenac, quinidine, calcitonin, amlodipine, ACE inhibitors, daclizumab,[4] and calcium channel blockers.

Relationship to systemic diseases

Granuloma annulare has been associated primarily with type I diabetes mellitus, but it is only rarely associated with type II diabetes mellitus and thyroid disease, based on an increased number of granuloma annulare patients with these diseases in small case series.[5]

Small case series have reported granuloma annulare to occur in association with malignancy, AIDS, and herpes zoster lesions. Although no definite patterns relating granuloma annulare and systemic disease have been thoroughly established, it has been suggested that an atypical histologic (vasculopathy or extravascular neutrophilia) or clinical presentation (unusual appearance or location) may indicate an associated disease. In the case of malignancy, a 2003 study by Li et al reviewed classic cases in the literature and could find no definite relationship between granuloma annulare and malignant neoplasms.[6]

Relationship with malignant diseases

Certain malignancies are accompanied by different mucocutaneous paraneoplastic syndromes. Lesions that mimic granuloma annulare or are histologically confirmed as granuloma annulare have occurred in association with the following:

Previous
 
 
Contributor Information and Disclosures
Author

Ruby Ghadially, MBChB, FRCP(C)Derm Professor, Department of Dermatology, University of California, San Francisco, School of Medicine

Ruby Ghadially, MBChB, FRCP(C)Derm is a member of the following medical societies: American Academy of Dermatology, Ontario Medical Association, Royal College of Physicians and Surgeons of Canada, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

Akos Z Szabo, MD Resident Physician, Department of Obstetrics and Gynecology, University of Heidelberg Medical Center, Germany

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Steven R Feldman, MD, PhD Professor, Departments of Dermatology, Pathology and Public Health Sciences, and Molecular Medicine and Translational Science, Wake Forest Baptist Health; Director, Center for Dermatology Research, Director of Industry Relations, Department of Dermatology, Wake Forest University School of Medicine

Steven R Feldman, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, North Carolina Medical Society, Society for Investigative Dermatology

Disclosure: Received honoraria from Amgen for consulting; Received honoraria from Abbvie for consulting; Received honoraria from Galderma for speaking and teaching; Received consulting fee from Lilly for consulting; Received ownership interest from www.DrScore.com for management position; Received ownership interest from Causa Reseasrch for management position; Received grant/research funds from Janssen for consulting; Received honoraria from Pfizer for speaking and teaching; Received consulting fee from No.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Arash Taheri, MD Research Fellow, Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

Amit Garg, MD Director of Clinical Elective in Dermatology, Assistant Professor, Department of Internal Medicine, Division of Dermatology, University of Massachusetts Medical School

Amit Garg, MD is a member of the following medical societies: American Academy of Dermatology and American Medical Student Association/Foundation

Disclosure: Abbott Immunology Honoraria Speaking and teaching; Centocor Grant/research funds Other; RegenRx Grant/research funds Other

References
  1. Felner EI, Steinberg JB, Weinberg AG. Subcutaneous granuloma annulare: a review of 47 cases. Pediatrics. 1997 Dec. 100(6):965-7. [Medline].

  2. Penas PF, Jones-Caballero M, Fraga J, Sanchez-Perez J, Garcia-Diez A. Perforating granuloma annulare. Int J Dermatol. 1997 May. 36(5):340-8. [Medline].

  3. Ghadially R. Granuloma annulare, actinic granuloma. Arndt K, et al, eds. Cutaneous Medicine and Surgery. WB Saunders Co; 1996. 438-443.

  4. Mehta LR, Rose JW. Recurrent granuloma annulare during treatment with daclizumab. Mult Scler. 2009 Apr. 15(4):527-8. [Medline].

  5. Kakourou T, Psychou F, Voutetakis A, Xaidara A, Stefanaki K, Dacou-Voutetakis C. Low serum insulin values in children with multiple lesions of granuloma annulare: a prospective study. J Eur Acad Dermatol Venereol. 2005 Jan. 19(1):30-4. [Medline].

  6. Li A, Hogan DJ, Sanusi ID, Smoller BR. Granuloma annulare and malignant neoplasms. Am J Dermatopathol. 2003 Apr. 25(2):113-6. [Medline].

  7. O'Brien JP, Regan W. Actinically degenerate elastic tissue is the likely antigenic basis of actinic granuloma of the skin and of temporal arteritis. J Am Acad Dermatol. 1999 Feb. 40(2 Pt 1):214-22. [Medline].

  8. De Maeseneer M, Vande Walle H, Lenchik L, Machiels F, Desprechins B. Subcutaneous granuloma annulare: MR imaging findings. Skeletal Radiol. 1998 Apr. 27(4):215-7. [Medline].

  9. Shehan JM, El-Azhary RA. Magnetic resonance imaging features of subcutaneous granuloma annulare. Pediatr Dermatol. 2005 Jul-Aug. 22(4):377-8. [Medline].

  10. Blume-Peytavi U, Zouboulis CC, Jacobi H, Scholz A, Bisson S, Orfanos CE. Successful outcome of cryosurgery in patients with granuloma annulare. Br J Dermatol. 1994 Apr. 130(4):494-7. [Medline].

  11. Sniezek PJ, DeBloom JR 2nd, Arpey CJ. Treatment of granuloma annulare with the 585 nm pulsed dye laser. Dermatol Surg. 2005 Oct. 31 (10):1370-3. [Medline].

  12. Sliger BN, Burk CJ, Alvarez-Connelly E. Treatment of granuloma annulare with the 595 nm pulsed dye laser in a pediatric patient. Pediatr Dermatol. 2008 Mar-Apr. 25 (2):196-7. [Medline].

  13. Liu A, Hexsel CL, Moy RL, Ozog DM. Granuloma annulare successfully treated using fractional photothermolysis with a 1,550-nm erbium-doped yttrium aluminum garnet fractionated laser. Dermatol Surg. 2011 May. 37 (5):712-5. [Medline].

  14. Bronfenbrener R, Ragi J, Milgraum S. Granuloma annulare treated with excimer laser. J Clin Aesthet Dermatol. 2012 Nov. 5 (11):43-5. [Medline].

  15. Passeron T, Fusade T, Vabres P, Bousquet-Rouaud R, Collet-Vilette AM, Dahan S, et al. Treatment of granuloma annulare with the 595-nm pulsed dye laser, a multicentre retrospective study with long-term follow-up. J Eur Acad Dermatol Venereol. 2011 Dec 21. [Medline].

  16. Harth W, Linse R. Topical tacrolimus in granuloma annulare and necrobiosis lipoidica. Br J Dermatol. 2004 Apr. 150(4):792-4. [Medline].

  17. Jain S, Stephens CJ. Successful treatment of disseminated granuloma annulare with topical tacrolimus. Br J Dermatol. 2004 May. 150(5):1042-3. [Medline].

  18. Rigopoulos D, Prantsidis A, Christofidou E, Ioannides D, Gregoriou S, Katsambas A. Pimecrolimus 1% cream in the treatment of disseminated granuloma annulare. Br J Dermatol. 2005 Jun. 152(6):1364-5. [Medline].

  19. Lopez-Navarro N, Castillo R, Gallardo MA, Alcaide A, Matilla A, Herrera E. Successful treatment of perforating granuloma annulare with 0.1% tacrolimus ointment. J Dermatolog Treat. 2008. 19 (6):376-7. [Medline].

  20. Grieco T, Cantisani C, Faina P, Cantoresi F, Lacobellis F, Silvestri E, et al. Tacrolimus 0.1% and granuloma annulare: description of three cases. J Eur Acad Dermatol Venereol. 2009 Dec. 23 (12):1445-6. [Medline].

  21. Gomez-Moyano E, Vera-Casaño A, Martinez S, Sanz A. Periorbital granuloma annulare successfully treated with tacrolimus 0.1% ointment. Int J Dermatol. 2014 Feb. 53 (2):e156-7. [Medline].

  22. Kuwahara RT, Naylor MF, Skinner RB. Treatment of granuloma annulare with topical 5% imiquimod cream. Pediatr Dermatol. 2003 Jan-Feb. 20(1):90. [Medline].

  23. Badavanis G, Monastirli A, Pasmatzi E, Tsambaos D. Successful treatment of granuloma annulare with imiquimod cream 5%: a report of four cases. Acta Derm Venereol. 2005. 85(6):547-8. [Medline].

  24. Errichetti E, Stinco G, Pegolo E, Patrone P. Generalized Granuloma Annulare in a Cirrhotic Patient Treated with Narrowband Ultraviolet B Therapy. Indian J Dermatol. 2016 Jan-Feb. 61 (1):127. [Medline].

  25. Ine K, Kabashima K, Koga C, Kobayashi M, Tokura Y, Kabashima K. Eruptive generalized granuloma annulare presenting with numerous micropapules. Int J Dermatol. 2010 Jan. 49 (1):104-5. [Medline].

  26. Inui S, Nishida Y, Itami S, Katayama I. Disseminated granuloma annulare responsive to narrowband ultraviolet B therapy. J Am Acad Dermatol. 2005 Sep. 53 (3):533-4. [Medline].

  27. Samson Yashar S, Gielczyk R, Scherschun L, Lim HW. Narrow-band ultraviolet B treatment for vitiligo, pruritus, and inflammatory dermatoses. Photodermatol Photoimmunol Photomed. 2003 Aug. 19 (4):164-8. [Medline].

  28. Yong A, Chong WS, Pan JY. Disseminated granuloma annulare responding to narrowband UVB phototherapy. Photodermatol Photoimmunol Photomed. 2016 Mar. 32 (2):107-9. [Medline].

  29. Mikami E, Yanase M, Ito M, Kanzaki A, Saeki H. Generalized granuloma annulare successfully treated with narrowband ultraviolet B and anti-hepatitis C virus therapy. J Dermatol. 2016 Feb 19. [Medline].

  30. Pavlovsky M, Samuelov L, Sprecher E, Matz H. NB-UVB phototherapy for generalized granuloma annulare. Dermatol Ther. 2015 Dec 2. [Medline].

  31. Kerker BJ, Huang CP, Morison WL. Photochemotherapy of generalized granuloma annulare. Arch Dermatol. 1990 Mar. 126(3):359-61. [Medline].

  32. Batchelor R, Clark S. Clearance of generalized papular umbilicated granuloma annulare in a child with bath PUVA therapy. Pediatr Dermatol. 2006 Jan-Feb. 23 (1):72-4. [Medline].

  33. Grundmann-Kollmann M, Ochsendorf FR, Zollner TM, Tegeder I, Kaufmann R, Podda M. Cream psoralen plus ultraviolet A therapy for granuloma annulare. Br J Dermatol. 2001 May. 144 (5):996-9. [Medline].

  34. Browne F, Turner D, Goulden V. Psoralen and ultraviolet A in the treatment of granuloma annulare. Photodermatol Photoimmunol Photomed. 2011 Apr. 27 (2):81-4. [Medline].

  35. Looney M, Smith KM. Isotretinoin in the treatment of granuloma annulare. Ann Pharmacother. 2004 Mar. 38(3):494-7. [Medline].

  36. Schleicher SM, Milstein HJ. Resolution of disseminated granuloma annulare following isotretinoin therapy. Cutis. 1985 Aug. 36 (2):147-8. [Medline].

  37. Schleicher SM, Milstein HJ, Lim SJ, Stanton CD. Resolution of disseminated granuloma annulare with isotretinoin. Int J Dermatol. 1992 May. 31 (5):371-2. [Medline].

  38. Tang WY, Chong LY, Lo KK. Resolution of generalized granuloma annulare with isotretinoin therapy. Int J Dermatol. 1996 Jun. 35 (6):455-6. [Medline].

  39. Sahin MT, Türel-Ermertcan A, Oztürkcan S, Türkdogan P. Generalized granuloma annulare in a patient with type II diabetes mellitus: successful treatment with isotretinoin. J Eur Acad Dermatol Venereol. 2006 Jan. 20 (1):111-4. [Medline].

  40. Pasmatzi E, Georgiou S, Monastirli A, Tsambaos D. Temporary remission of disseminated granuloma annulare under oral isotretinoin therapy. Int J Dermatol. 2005 Feb. 44 (2):169-71. [Medline].

  41. Adams DC, Hogan DJ. Improvement of chronic generalized granuloma annulare with isotretinoin. Arch Dermatol. 2002 Nov. 138 (11):1518-9. [Medline].

  42. Piaserico S, Zattra E, Linder D, Peserico A. Generalized granuloma annulare treated with methylaminolevulinate photodynamic therapy. Dermatology. 2009. 218(3):282-4. [Medline].

  43. Weisenseel P, Kuznetsov AV, Molin S, Ruzicka T, Berking C, Prinz JC. Photodynamic therapy for granuloma annulare: more than a shot in the dark. Dermatology. 2008. 217(4):329-32. [Medline].

  44. Calzavara-Pinton PG, Rossi MT, Sala R, Italian Group For Photodynamic Therapy. A retrospective analysis of real-life practice of off-label photodynamic therapy using methyl aminolevulinate (MAL-PDT) in 20 Italian dermatology departments. Part 2: oncologic and infectious indications. Photochem Photobiol Sci. 2013 Jan. 12 (1):158-65. [Medline].

  45. Marcus DV, Mahmoud BH, Hamzavi IH. Granuloma annulare treated with rifampin, ofloxacin, and minocycline combination therapy. Arch Dermatol. 2009 Jul. 145(7):787-9. [Medline].

  46. Garg S, Baveja S. Monthly rifampicin, ofloxacin, and minocycline therapy for generalized and localized granuloma annulare. Indian J Dermatol Venereol Leprol. 2015 Jan-Feb. 81 (1):35-9. [Medline].

  47. Steiner A, Pehamberger H, Wolff K. Sulfone treatment of granuloma annulare. J Am Acad Dermatol. 1985 Dec. 13 (6):1004-8. [Medline].

  48. Czarnecki DB, Gin D. The response of generalized granuloma annulare to dapsone. Acta Derm Venereol. 1986. 66 (1):82-4. [Medline].

  49. Wolf F, Grezard P, Berard F, Clavel G, Perrot H. Generalized granuloma annulare and hepatitis B vaccination. Eur J Dermatol. 1998 Sep. 8 (6):435-6. [Medline].

  50. Saied N, Schwartz RA, Estes SA. Treatment of generalized granuloma annulare with dapsone. Arch Dermatol. 1980 Dec. 116 (12):1345-6. [Medline].

  51. Cannistraci C, Lesnoni La Parola I, Falchi M, Picardo M. Treatment of generalized granuloma annulare with hydroxychloroquine. Dermatology. 2005. 211 (2):167-8. [Medline].

  52. Simon M Jr, von den Driesch P. Antimalarials for control of disseminated granuloma annulare in children. J Am Acad Dermatol. 1994 Dec. 31 (6):1064-5. [Medline].

  53. Weber HO, Borelli C, Rocken M, Schaller M. Treatment of disseminated granuloma annulare with low-dose fumaric acid. Acta Derm Venereol. 2009. 89(3):295-8. [Medline].

  54. Shupack J, Siu K. Resolving granuloma annulare with etanercept. Arch Dermatol. 2006 Mar. 142 (3):394-5. [Medline].

  55. Kreuter A, Altmeyer P, Gambichler T. Failure of etanercept therapy in disseminated granuloma annulare. Arch Dermatol. 2006 Sep. 142 (9):1236-7; author reply 1237. [Medline].

  56. Hertl MS, Haendle I, Schuler G, Hertl M. Rapid improvement of recalcitrant disseminated granuloma annulare upon treatment with the tumour necrosis factor-alpha inhibitor, infliximab. Br J Dermatol. 2005 Mar. 152 (3):552-5. [Medline].

  57. Murdaca G, Colombo BM, Barabino G, Caiti M, Cagnati P, Puppo F. Anti-tumor necrosis factor-α treatment with infliximab for disseminated granuloma annulare. Am J Clin Dermatol. 2010 Dec 1. 11 (6):437-9. [Medline].

  58. Amy de la Breteque M, Saussine A, Rybojad M, Kramkimel N, Vignon Pennamen MD, Bagot M, et al. Infliximab in recalcitrant granuloma annulare. Int J Dermatol. 2016 Feb. 55 (2):220-2. [Medline].

  59. Rosmarin D, LaRaia A, Schlauder S, Gottlieb AB. Successful treatment of disseminated granuloma annulare with adalimumab. J Drugs Dermatol. 2009 Feb. 8(2):169-71. [Medline].

  60. Torres T, Pinto Almeida T, Alves R, Sanches M, Selores M. Treatment of recalcitrant generalized granuloma annulare with adalimumab. J Drugs Dermatol. 2011 Dec. 10(12):1466-8. [Medline].

  61. Min MS, Lebwohl M. Treatment of recalcitrant granuloma annulare (GA) with adalimumab: A single-center, observational study. J Am Acad Dermatol. 2016 Jan. 74 (1):127-33. [Medline].

  62. Mahmood T, Mansouri B, Menter A. Successful treatment of generalized granuloma annulare with adalimumab. Clin Exp Dermatol. 2015 Jul. 40 (5):537-9. [Medline].

  63. Werchau S, Enk A, Hartmann M. Generalized interstitial granuloma annulare--response to adalimumab. Int J Dermatol. 2010 Apr. 49 (4):457-60. [Medline].

  64. Gass JK, Todd PM, Rytina E. Generalized granuloma annulare in a photosensitive distribution resolving with scarring and milia formation. Clin Exp Dermatol. 2009 Jul. 34(5):e53-5. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.