eMedicine Specialties > Dermatology > Reactive & Inflammatory Dermatoses

Granuloma Annulare: Differential Diagnoses & Workup

Author: Ruby Ghadially, MBChB, FRCP(C)Derm, Professor, Department of Dermatology, University of California, San Francisco, School of Medicine
Coauthor(s): Akos Z Szabo, MD, Resident Physician, Department of Plastic and Hand Surgery, Freiburg University Medical Center; Amit Garg, MD, Director of Clinical Elective in Dermatology, Assistant Professor, Department of Internal Medicine, Division of Dermatology, University of Massachusetts Medical School
Contributor Information and Disclosures

Updated: Aug 26, 2009

Differential Diagnoses

Erythema Annulare Centrifugum
Erythema Elevatum Diutinum
Lichen Planus

Other Problems to Be Considered

Localized granuloma annulare
Annular lichen planus
Acute febrile neutrophilic dermatosis
Erythema annulare centrifugum
Erythema elevatum diutinum
Erythema migrans of Lyme disease
Fat necrosis
Giant cell arteritis8
Hansen disease (leprosy)
Mucocutaneous paraneoplastic syndrome
Necrobiosis lipoidica diabeticorum
Neonatal lupus erythematosus
Subacute cutaneous lupus erythematosus
Tinea corporis

Generalized granuloma annulare
Cutaneous metastases
Cutaneous paraneoplastic syndrome
Lichen myxedematous
Lichen planus
Sarcoidosis

Subcutaneous granuloma annulare

 Dermoid cyst
Erythema nodosum
Rheumatoid nodule

Perforating granuloma annulare
Elastosis perforans serpiginosa
Foreign body granuloma
Insect bites
Molluscum contagiosum
Pityriasis lichenoides
Perforating collagenosis

Actinic granuloma annulare
Erythema annulare centrifugum
Necrobiosis lipoidica diabeticorum
Sarcoidosis

Workup

Laboratory Studies

  • Laboratory studies are largely noncontributory in patients with granuloma annulare (GA). With a classic history and unremarkable physical examination findings (other than the presenting lesion[s]), no additional workup is necessary.
    • If, however, a thorough history is not available or systemic disease is considered likely, appropriate laboratory evaluations should be performed to exclude other diagnostic possibilities.
    • For example, in subcutaneous granuloma annulare, a CBC count, an erythrocyte sedimentation rate, and a rheumatoid factor study may assist in excluding other possible causes for nodules.

Imaging Studies

  • Imaging studies are not generally necessary in diagnosing granuloma annulare. However, radiographs, CT scans, or MRIs may be helpful in the evaluation of atypical subcutaneous lesions.
    • Radiographs of subcutaneous granuloma annulare show a nonspecific soft tissue mass without calcification.
    • On CT scans, subcutaneous granuloma annulare appears as a poorly defined mass with variable attenuation and variable contrast enhancement.
    • On MRIs, subcutaneous granuloma annulare appears as a mass with poorly defined margins that is limited to subcutaneous tissue. MRI findings may be suggestive of, but not diagnostic of, subcutaneous granuloma annulare.9,10

Procedures

  • Biopsy is recommended for a subcutaneous lesion and for an atypical presentation with respect to history (ie, rapid enlargement, pain) or location of lesion.

Histologic Findings

Early interstitial or incomplete granuloma annulare lesions show an interstitial pattern characterized by lymphocytes around vessels of the superficial and deep plexuses and by macrophages scattered between reticular dermal collagen bundles that are separated by mucin within which mast cells may be found. Mucin in granuloma annulare is hyaluronic acid and is visible in sections stained with hematoxylin and eosin as faintly basophilic stringy material. Its presence can be confirmed by staining with colloidal iron or Alcian blue at pH 2.5.

Fully evolved granuloma annulare lesions and deep subcutaneous granuloma annulare nodules demonstrate palisaded granulomatous dermatitis or a septal and lobular panniculitis, respectively. Macrophages surround acellular necrobiotic areas in which collagen bundles are thinned, or they sometimes have a pale, homogeneous, light-blue appearance, the latter of which is due to the presence of mucin.

In many cases of subcutaneous granuloma annulare, and in some dermal infiltrates, the centers of granulomas contain degenerated, homogeneous-appearing collagen and are deeply eosinophilic. In some sections, necrotic small vessels in the centers of palisaded foci are surrounded by nuclear dust. Presence of fibrinogen can be shown by direct immunofluorescence in the centers of palisaded granulomas. In perforating lesions, necrobiotic material is extruded through focal perforations. Epidermal hyperplasia at the edge of the perforation forms a pseudochannel communicating with an underlying necrobiotic granuloma.

Rare cases of nonnecrobiotic, sarcoidal, or tuberculoid granuloma annulare are also described.
Actinic annulare, also known as annular elastolytic giant cell granuloma, may lack the classic palisaded arrangement observed in granuloma annulare. Although elastosis is abundant in the mid dermis outside the granuloma, elastic tissue is absent from the center of the annulus. Giant cells frequently abut elastotic tissue, and phagocytosed elastotic fibers are noted in histiocytic cells at the advancing edge. Collagen has a normal appearance outside the lesion but a finely fibrillar pattern within the annulus. Mucin deposition is not increased as it is in granuloma annulare. Thus, actinic annulare can be distinguished histologically from granuloma annulare by a preponderance of giant cells in relation to elastotic tissue, by absence of mucin, and, occasionally, by absence of palisading histiocytes around granulomas.

More on Granuloma Annulare

Overview: Granuloma Annulare
Differential Diagnoses & Workup: Granuloma Annulare
Treatment & Medication: Granuloma Annulare
Follow-up: Granuloma Annulare
References
[ CLOSE WINDOW ]

References

  1. Argent JD, Fairhurst JJ, Clarke NM. Subcutaneous granuloma annulare: four cases and review of the literature. Pediatr Radiol. 1994;24(7):527-9. [Medline].

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

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

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

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

  6. 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. Jan 2005;19(1):30-4. [Medline].

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

  8. 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. Feb 1999;40(2 Pt 1):214-22. [Medline].

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

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

  11. 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. Apr 1994;130(4):494-7. [Medline].

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

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

  14. 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. Jun 2005;152(6):1364-5. [Medline].

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

  16. 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].

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

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

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

  20. 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].

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

  22. 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].

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

  24. [Guideline] Frykberg RG, Zgonis T, Armstrong DG, et al. Diabetic foot disorders. A clinical practice guideline (2006 revision). J Foot Ankle Surg. Sep-Oct 2006;45(5 Suppl):S1-66. [Medline].

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

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

granuloma annulare, GA, dermatosis, dermal papules, annular plaques, localized granuloma annulare, generalized granuloma annulare, subcutaneous granuloma annulare, perforating granuloma annulare, arcuate dermal erythema, actinic granuloma, AG, annular elastolytic giant cell granuloma, Miescher granuloma, type IV cell-mediated immunity, immune complex vasculitis

[ CLOSE WINDOW ]

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, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Coauthor(s)

Akos Z Szabo, MD, Resident Physician, Department of Plastic and Hand Surgery, Freiburg University Medical Center
Disclosure: Nothing to disclose.

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

Medical Editor

James J Nordlund, MD, Professor Emeritus, Department of Dermatology, University of Cincinnati College of Medicine
James J Nordlund, MD is a member of the following medical societies: American Academy of Dermatology, Sigma Xi, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Rosalie Elenitsas, MD, Herman Beerman Associate Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System
Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology and American Society of Dermatopathology
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.