Non-infectious Granulomatous Diseases of the Skin and their Associated Systemic Diseases: An Evidence-based Update to Important Clinical Questions

Elena Balestreire Hawryluk; Leonid Izikson; Joseph C. English III

Disclosures

Am J Clin Dermatol. 2010;11(3):171-181. 

In This Article

1. is Granuloma Annulare Associated with Hematopoietic and Solid Malignancy?

GA is a benign inflammatory condition that often presents with a ring of multiple small, erythematous or flesh-colored, firm papules on the dorsal surface of the hands and/or feet. GA is further classified according to lesion morphology into subgroups: localized, macular or patch, and atypical (consisting of perforating, subcutaneous, disseminated, palmar, photodistributed, or generalized forms). Lesions are generally non-pruritic and self-limited, often resolvingwithout treatmentwithin 2 years, though a variety of treatments have been attempted.

In 2003, Li et al.[11] published a summary review of 14 case reports and two correlation studies to explore the association of GA with malignant neoplasms, and found a diagnosis of neoplasm ranging from 18 months prior to 7 years after onset of GA. The coexistent neoplasms included carcinomas, lymphomas, and acute myeloid leukemia, while separate manuscripts described additional cases of GA in patients with schwannoma,[12] visceral malignancy,[13] Hodgkin disease,[14] and chronic myelomonocytic leukemia.[15] While Li et al.[11] found no definite relationship between GA and malignancy, they suggest the investigation of underlying malignancies particularly for older patients with skin lesions that histologically, but not necessarily clinically, resemble GA.

In a retrospective study of Mayo Clinic GA patients with over 20 years of follow-up, most patients remained relatively healthy and did not develop rare diseases, but rather were afflicted with common conditions or diseases of aging, such as hypertension, diabetes, and atherosclerosis.[16] Only one of the 32 patients in the study had any type of malignancy: non- Hodgkin lymphoma. Two correlation studies (albeit with disadvantages in terms of assessing relationships among diseases) revealed no statistical relationship between GA and malignancy.[17,18] It was suggested that the increased incidence of malignancy previously reported may reflect an overall increased prevalence of malignancy in the older populations studied, although it has been noted that GA has been reported in children with leukemia or lymphoma.[11]

Although no statistical relationship was found, the 1989 correlation study by Dabski and Winkelmann[18] reported an incidence of malignant disease of 11.9% and 18.2% in patients with annular GA and atypical non-annular lesions, respectively. Importantly, IGD could be misdiagnosed as GA, and IGD is in fact associated with malignancy,[19] which may account for some of the discrepancies in reported associations. Regardless, GA has been included as one of several conditions with dermatologic manifestations, along with relapsing polychondritis, sarcoidosis, and systemic lupus erythematosus, which may signify an underlying hematologic or other type of malignancy.[20]

A clinically similar, non-infectious granulomatous disease is annular elastolytic giant cell granuloma (AEGCG), which is often regarded as 'GA in sun-exposed areas.' It has been postulated that AEGCG is caused by severe degeneration of skin elastic tissues in response to actinic injury.[21] While the clinical features of AEGCG and GA are similar and these conditions are often treated with the same approach, they are histologically distinct. Unlike GA, AEGCGis characterized by a central zone of dermal atrophy that lacks elastic tissue; additionally, AEGCG lesions do not show necrobiosis and palisading granuloma.[22] Like GA, the literature includes several reports that present an association of AEGCG with malignancy, for example, an AEGCG patient who also had adult T-cell leukemia.[23] A particularly interesting case report described a patient in whom AEGCG lesions heralded the onset and recurrence of acute myelogenous leukemia.[24] Therefore, the clinically similar AEGCG lesions should also prompt an appropriate investigation for underlying malignancy.

1.1 Summary and Recommendations

No causative relationship between malignancy and GA has been substantiated by the literature. However, there is evidence that GA has presented in patients with both hematopoietic and solid malignancies of varying types. Patients with atypical GA, older patients with GA, and patients with GA-like granulomatous dermatitis should undergo age-appropriate screening tests for solid and hematologic malignancy, as well as a screening for any underlying immunosuppressed state that may otherwise predispose these patients to malignancy.

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