Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Art & Psychiatry
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Conference Oration
Conference Summary
Continuing Medical Education
Cosmetic Dermatology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
Editor Speaks
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Miscellaneous Letter
Net Case
Net case report
Net Image
Net Letter
Net Quiz
Net Study
New Preparations
News & Views
Observation Letter
Observation Letters
Original Article
Original Contributions
Pattern of Skin Diseases
Pediatric Dermatology
Pediatric Rounds
Presedential Address
Presidential Address
Presidents Remarks
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Review Article
Review Articles
Revision Corner
Self Assessment Programme
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Special Article
Specialty Interface
Study Letter
Study Letters
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapy Letter
Therapy Letters
View Point
What’s new in Dermatology
View/Download PDF

Translate this page into:

Case Report
doi: 10.4103/0378-6323.51251
PMID: 19439883

Generalized granuloma annulare in a patient with myelocytic leukemia and chronic hepatitis B virus infection

Ulku Askin, Murat Durdu, Engin Senel
 Department of Dermatology, Baskent University Faculty of Medicine, Ankara, Turkey

Correspondence Address:
Engin Senel
Baskent University Faculty of Medicine, Department of Dermatology, 5. sokak No: 48 Bahcelievler, Ankara 06490
How to cite this article:
Askin U, Durdu M, Senel E. Generalized granuloma annulare in a patient with myelocytic leukemia and chronic hepatitis B virus infection. Indian J Dermatol Venereol Leprol 2009;75:287-289
Copyright: (C)2009 Indian Journal of Dermatology, Venereology, and Leprology


Granuloma annulare is a granulomatous disorder of the dermis and subcutaneous tissue, with different clinical types. Generalized granuloma annulare is a rarely encountered clinical entity. We describe a 60-year-old woman with a 4-month history of generalized annular lesions. She had a history of myelocytic leukemia and chronic hepatitis B virus infection. To date, both acute myelocytic leukemia and hepatitis B virus infection have been described independently in association with generalized granuloma annulare but have never been described together in association with generalized granuloma annulare. Probable etiological causes of granuloma annulare are discussed in our patient.
Keywords: Generalized granuloma annulare, Acute myelocytic leukemia, Hepatitis B, Tzanck smear


Granuloma annulare (GA) is an idiopathic and benign granulomatous disorder with classic features including single or multiple papules with a tendency to form annular lesions. There is a wide spectrum of clinical subsets including localized, generalized, perforating, and subcutaneous types. Generalized granuloma annulare (GGA) is a rare variant of GA, observed predominantly in women aged 30 to 70 years. Although the pathogenesis of GGA is unknown, it has been described in patients with diabetes mellitus, malignancies, thyroid diseases, hepatitis B and C virus infections, medications, and acquired immunodeficiency syndrome. [1],[2],[3],[4] Here, we report GGA in a patient with a history of acute myelocytic leukemia and chronic hepatitis B virus (HBV) infection and describe the Tzanck smear findings of GA.

Case Report

A 60-year-old woman presented at our institution with a 4-month history of generalized annular lesions. The patient had been diagnosed as having acute myelocytic leukemia (AML M1-2) two years earlier and had been treated with chemotherapy (cytarabine); however, her leukemia did not respond to treatment. She also had chronic HBV infection for 2 years and had been treated with oral lamivudine (100mg/day) for 6 months. A dermatologic examination revealed symmetrical, generalized, yellow-brown-to-erythematous papules and annular plaques measuring 0.3 to 3cm distributed predominantly over her back, chest, and upper extremities [Figure - 1]. Histopathological examination showed that the mucin-positive granulomatous infiltrate included lymphocytes and multinucleated giant cells in the upper and mid-dermis. The results of biopsy staining and cultures for fungi and mycobacteria were negative. Polymerase chain reaction (PCR) analysis for HBV DNA was negative. A Tzanck smear disclosed granuloma with mucin and Langhans-type giant cell [Figure - 2]. The findings of histopathology and Tzanck smear were consistent with the diagnosis of GA.

Results of serologic tests for hepatitis HBsAg and anti- HBe were positive, whereas those of HBeAg, anti- HBs and anti-HCV were negative. No significant changes were seen in renal, hepatic or thyroid function tests, or on a urine analysis. The serum glucose level was normal. Laboratory analysis demonstrated the following values: Hemoglobin, 10.9g/dL; leukocyte, 2680/mm 3 ; and platelet count, 4,91,000/mm 3 . Peripheral smear showed 5% atypical mononuclear cells. Bone marrow aspiration revealed blastic infiltration, dysmyelopoiesis and dyserythropoiesis. Results of a chest radiograph and abdominal ultrasonographic examination were normal.

She was treated with a topical steroid (clobetasol propionate), and the skin lesions completely resolved 3 months later [Figure 3a] and [Figure 3b]. Treatment with cytarabine and lamivudine was continued. No recurrence was seen at 1-year follow-up.


GA is a benign, usually self-limited, inflammatory dermatosis of unknown etiology. Clinical variants of GA are localized, generalized, subcutaneous and perforating. GGA is a rare variant that represents 8.5% to 15% of all cases of GA. GGA presents clinically with skin-colored, erythematous or violaceous dermal papules and/or small annular plaques with slightly elevated borders. In nearly 70% of cases, these plaques are asymptomatic, but they may cause pruritus or a burning sensation. The pathogenesis of GA is still not well understood. The antigenic stimulus that initiates the delayed-type hypersensitivity reaction is unknown, but various associations have been reported, which include diabetes mellitus, malignancies, thyroid diseases, hepatitis B and C virus infection, medications and acquired immunodeficiency syndrome. [1],[2],[3],[4],[5]

Harman et al. , first reported an association of GA and malignancy in 1977. [6] Later, in a series of 100 patients with GGA, Dabski and Winkelmann found 14 cases of internal malignancies preceding or following the skin eruption; however, they rejected a causative relationship between the 2 disorders owing to the wide variation in time between their onsets. [2] The mechanism of the association between GA and malignancies is unknown. It is speculated that GA results from an immunologic reaction stimulated by an unidentified tumor antigen. These patients may have decreased cell-mediated immunity due to tumors. Tumor cells may directly or indirectly cause secretion of cytokines; cytokine activation of fibroblasts might produce an inflammatory reaction that mediates the formation of a granuloma. In addition to patients with malignancy and tumor-related immunodeficiency, GA has also been observed in individuals with deficiencies in cell-mediated immunity, such as patients with HIV infection [7] or sarcoidosis; [8] this suggests that immunologic factors may have a role in the development of malignancy-associated GA.

In most patients with malignancy, a diagnosis of cancer had previously been established, and the appearance of GA lesions was not temporally associated with detecting an underlying malignancy. [1] Although uncommon, GA may be temporally associated with detecting a previously undiagnosed malignancy or recurrent metastatic disease, and resolution of the dermatosis may be temporally associated with successful treatment of that cancer. [1]

Among the hematologic malignancies, malignant lymphoma has been commonly reported, but there is only one report in the literature of GGA with acute myelocytic leukemia. [9] In our patient, this association might have been coincidental, because the skin lesions resolved with topical treatment after 3 months, although the leukemia did not respond to treatment.

There is one report in the literature of GGA associated with chronic HBV infection, suggesting a link between GGA and HBV infection, which was further confirmed by HBV-DNA in the biopsy papules of GGA. [4] Moreover, a GA-like eruption caused by chronic hepatitis C virus infection and hepatitis B vaccination has been reported.[10] In our patient, although the DNA of HBV in the biopsy specimen and the serum HBV DNA quantitative PCR assay showed negative results, the eruption also could have been caused by HBV infection that provoked a cellular immune response via T lymphocytes.

The time interval between GA and cancer and HBV infection cannot be exactly evaluated, because both of these are usually asymptomatic during the early stages and are often ignored. Therefore, the association must be readily clarified by further studies and new case reports.

The Tzanck smear can be used as a cytologic diagnostic tool for granulomatous diseases. The Tzanck smear will demonstrate granulomas and Langhans-type giant cells in sarcoidosis and tuberculosis. In our case, cytologic examination showed Langhans giant cells, granulomas and mucinous materials. The Tzanck smear findings were concordant with the histopathological findings and are the first such findings to be described in the literature for GA.

In conclusion, GA with acute myelocytic leukemia and HBV infection is rare. Clinicians should be aware of underlying cancers, especially in elderly patients with GA.

Cohen PR. Granuloma annulare associated with malignancy. South Med J 1997;90:1056-9.
[Google Scholar]
Dabski K, Winkelmann RK. Generalized granuloma annulare: Clinical and laboratory findings in 100 patients. J Am Acad Dermatol 1989;20:39-47.
[Google Scholar]
Shimizu S, Yasui C, Tsuchiya K. Atypical generalized granuloma annulare associated with two visceral cancers. J Am Acad Dermatol 2006;54:S236-8.
[Google Scholar]
Ma HJ, Zhu WY, Yue XZ. Generalized granuloma annulare associated with chronic hepatitis B virus infection. J Eur Acad Dermatol Venereol 2006;20:186-9.
[Google Scholar]
Lim AC, Hart K, Murrell D. A granuloma annulare-like eruption associated with the use of amlodipine. Australas J Dermatol 2002;43:24-7.
[Google Scholar]
Harman RR. Hodgkin's disease, seminoma of testicle and widespread granuloma annulare. Br J Dermatol 1977;97:S50-1.
[Google Scholar]
Cohen PR, Grossman ME, Silvers DN, DeLeo VA. Human immunodeficiency virus-associated granuloma annulare. Int J STD AIDS 1991;2:168-71.
[Google Scholar]
Umbert P, Winkelmann RK. Granuloma annulare and sarcoidosis. Br J Dermatol 1977;97:481-6.
[Google Scholar]
Vestey JP, Turner M, Biddlestone L, McLaren K, Goulden N, Hunter JA. Disseminated cutaneous granulomatous eruptions associated with myelodysplastic syndrome and acute myeloid leukaemia. Clin Exp Dermatol 1993;18:559-63.
[Google Scholar]
Wolf F, Grezard P, Berard F, Clavel G, Perrot H. Generalized granuloma annulare and hepatitis B vaccination. Eur J Dermatol 1998;8:435-6.
[Google Scholar]

Fulltext Views

PDF downloads
Show Sections