O'Brien Actinic Granuloma: A Case Report and Brief Review of Literature.

O'Brien first described the actinic granuloma in 1975, as an infrequent granulomatous disorder occurring in sun-exposed skin, with a slow but often self-limited course. Ever since its initial description, the actinic physiopathogenic hypothesis has been debated by many authors. We report a 60-year-old female rural worker that presented with a 14 × 7 cm annular lesion with erythematous elevated borders and an atrophic center on the right calf. The lesion was evolving for 2 years, and histopathology confirmed actinic granuloma. She started acitretin with halting of disease progression after 6 months of therapy. Our case can also be associated to actinic damage, despite its unusual location, therefore highlighting the role of solar elastosis in the development of O'Brien actinic granuloma.

What was known?

O’Brien actinic granuloma is a rare granulomatous dermatosis. It is now considered an independent entity from granuloma annulare but controversy still exists regarding association with systemic illnesses. Its relation to photodamage is a matter of debate although most lesions show photodistribution.

Introduction

Actinic granuloma (AG) was first described by O’Brien in 1975, as a rare granulomatous disease.[1] Lesions present on sun-exposed sites, most commonly on the face, neck and scalp with a slight predominance in middle-aged women. They are generally asymptomatic, single or multiple, annular or polycyclic lesions that can measure up to 6 cm, showing slow centrifugal expansion, with an erythematous elevated edge and a hypopigmented, atrophic center.[2]

Despite initial debate regarding whether AG would represent a variant of granuloma annulare, it is now considered a distinct entity, believed to be related to photo damage. We report a case that further corroborates this hypothesis.

Case Report

A 60-year-old female rural worker presented with an annular lesion with elevated, erythematous borders and a hypopigmented, atrophic center, located on the right calf [Figure 1]. It measured approximately 14 × 7 cm and was slowly extending centrifugally for more than 2 years, despite treatment with systemic and topical antifungals.

Figure 1

Annular lesion with erythematous scalloped borders and an atrophic center occupying the right calf

The patient had a previous history of dyslipidemia, treated with atorvastatine, 40 mg daily. She had no history of diabetes mellitus, temporal arteritis, polymyalgia rhematica, relapsing polychondritis and pseudoxanthoma elasticum. She had worked in the fields for several decades, usually with exposed legs due to the use of skirts.

Complete blood count, erythrocyte sedimentation rate, chemistry panel with renal and hepatic function and nuclear antibodies were all negative or within normal range. Microscopic examination of skin scrapings was negative for fungal elements.

A biopsy taken across the border of the lesion showed a superficial dermal granulomatous infiltrate with multinucleated giant cells that exhibited elastophagocytosis [Figure 2]. With Verhoeff van Gieson stain, solar elastosis in the upper and mid dermis became evident, as well as phagocytosis of elastotic fibers [Figure 3].

Figure 2

Multinucleated giant cells composing a granulomatous infiltrate occupying the upper and mid dermis, with foci of elastophagocytosis (arrow), adjacent to areas of solar elastosis (star). (H and E, original magnification ×200)

Figure 3

A detailed image of elastophagocytosis using Verhoeff van Gieson stain. (original magnification ×400)

A diagnosis of O’ Brien AG was made, and the patient started clobetasol 0.05% ointment, that she maintained daily for 2 months with slow but progressive extension of the lesion.

She then began acitretin 25 mg daily for 6 months, with stabilization of the lesion and further discontinuation of therapy.

Discussion

According to O’Brien, AG consisted of a granulomatous reaction to solar damage, with histiocytes and foreign-body type multinucleated cells engulfing elastotic fibers within a background of solar elastosis. The absence of elastic fibers would characterize the center of the granuloma, corresponding clinically to the atrophic, hypopigmented center of the lesion.

He concluded that this was also the likely diagnosis for other previously described entities such as “Miescher's granuloma of the face” and “necrobiosis lipoidica presenting on the face and scalp” and in 1985 he further characterized AG in four subvariants[3], the original giant cell annular form, the necrobiotic form, the histiocytic and the sarcoidal variant.

Predilection for sun-exposed skin and a three-zone typical histopathology were the clinical and pathological hallmarks of AG and seemed to support the “actinic hypothesis” proposed by O’Brien.

Hypothetically, elastotic fibers resulting from actinic radiation could represent an antigenic trigger for an autoimmune granulomatous reaction that would then ensue. A report associating AG with giant cell temporal arteritis (GCA)[4] further strengthened this belief.

In GCA, actinic damage of the internal elastic lamina of the artery would occur with surrounding presence of matrix metalloproteinase 9 and macrophages.

While McGrae was demonstrating a T-helper cell infiltrate[5] with perivascular and interstitial distribution amidst the granulomatous reaction of AG, also elastase-derived elastin peptides were reported to be high in the sera of patients with GCA,[6] being targeted by T-helper lymphocytes, in an analogous manner to what was happening in AG.

The actinic pathogenesis, however, was opposed by Ragaz and Ackerman that viewed elastolytic granuloma as a variant of granuloma annulare in solar-damaged skin.

Others preferred the descriptive term of annular elastolytic giant cell granuloma (AEGCG), stating its independent classification from granuloma annulare (highlighted by the absence of mucin deposition) but not finding definite evidence for the actinic hypothesis. They believed that the association between solar elastosis and granulomatous inflammation should not necessarily imply a cause–effect relationship, despite noting some cases with excess of actinically damaged elastic fibers.

Case reports showing the occurrence of the granuloma on sun-protected skin further supported this idea. Currently, the denomination of AEGCG is still in use, with disregard for O’Brien's original view on the actinic pathogenesis

Recently, reports associating lesions of AG in skin affected by late-onset X-linked protoporphyria[7] and vitiligo[8] again corroborate the causative role of elastotic fibers and solar damage.

Our case displays a typical lesion with typical histopathology in an unusual anatomic location. However, in our patient, this location was subjected to chronic sun exposure, in accordance to most described reports.

Other associated entities include diabetes and leukemia, polymialgia rheumatica, relapsing polychondritis and pseudoxanthoma elasticum, although the relevance of these associations remains unproven.

O’Brien AG is reported to have a slow but self-limiting course and can take up to 10 years to resolve. Nonetheless, because lesions are often extensive and frequently affect sites of cosmetic importance such as the face, therapy is necessary in order to prevent new lesions and enlargement of existing ones.

Although oral and topical corticosteroid therapy is generally ineffective, there are reports of successful treatment with systemic retinoids, such as acitretin[9] but also with isotretinoin.[10] In our patient, the progression of the lesion was halted after 6 months of the former drug and didn’t return on its suspension. Nonetheless, we cannot prove whether this was due to acitretin or to the self-limiting nature of the disease.

AG is currently a widely accepted entity, even though its pathogenesis is not fully clarified.

Its specific histopathologic findings suffice to establish it outside the granuloma annulare spectrum, however, the full grasp of the role of actinic damage and its consequences not only in the skin, but also systemically, still remains elusive.

What is new?

The role of actinic damage has been favored by the concomitant occurrence of O’Brien's actinic granuloma, protoporphyria and vitiligo. Its diagnosis should be considered in patients presenting with annular plaques with photodistribution even if they are located in an unusual site. Despite its slow self-limiting course, therapeutic options include systemic retinoids, namely acitretin.