A report of disseminated actinic granuloma: An unusually extensive presentation

Abstract

In this report, a case of disseminated actinic granuloma in a 50-year-old female with type 2 diabetes mellitus is described. This case is unique due to the unusually extensive cutaneous involvement of the face, neck, trunk, and extremities at initial presentation. The lesions were in a striking photo-distribution, highlighting ultraviolet light as an important environmental trigger for this process. Interestingly, the patient refused the recommended systemic therapy with hydroxychloroquine, despite her significant burden of skin disease. This refusal stems from an unexpected reluctance on the part of the patient to take this medication due to the publicity and media coverage of side effects associated with inappropriate prescribing of this drug during the COVID-19 pandemic, presenting a new and surprising treatment barrier that clinicians may need to overcome.

Introduction

Granulomatous skin diseases represent a clinically and histologically heterogenous group of autoinflammatory, reactive, and infectious diseases including sarcoidosis, necrobiosis lipoidica, granuloma annulare (GA), interstitial granulomatous dermatitis, and mycobacterial infections. ¹ While originally thought to be variants of GA, actinic granuloma and annulare elastolytic giant cell granuloma (AEGCG) were separately described in the 1970s as distinct entities distinguishable from GA based on unique histological features.^2–4 The majority of presentations of actinic granuloma and AEGCG reported in the medical literature are clinically localized. Because these entities share overlapping clinicopathologic presentations, they likely represent variants of the same disease process with actinic granuloma specifically associated with UV exposure. Herein, we describe a case of extensive actinic granuloma with disseminated, photo-distributed lesions and provide discussion of this unique form of granulomatous dermatitis.

Case report

A 50-year-old female with a past medical history of hypertension and type 2 diabetes mellitus presented for evaluation of a progressively worsening skin eruption involving the face, neck, upper back, chest, arms, hands, and lower legs. The patient first noted a lesion on the left extensor forearm 8 years prior. At that time, she was clinically diagnosed with GA and treated with intralesional injection of triamcinolone by an outside provider. The treated lesion improved temporarily but recurred over time. New lesions developed and spread, and she was treated with repeat injections of intralesional triamcinolone, in addition to oral dapsone, topical fluocinonide ointment, and doxycycline, all without improvement.

At the time of presentation to our institution, she reported extensive lesions on the head, neck, trunk, and extremities that were red, raised, and pruritic. The patient denied constitutional or systemic symptoms. She also reported frequent recreational sun exposure and stated that she typically donned sleeveless, scoop-neck tank tops outdoors. Although the patient had previously been diagnosed with diabetes mellitus, she attempted to control it with diet alone and was not on treatment at the time of presentation. She self-reported that her last hemoglobin A1c was 7.

On physical examination, the patient had numerous erythematous, annular patches and plaques disseminated on the temples, lateral cheeks, lateral neck, superior chest, central superior upper back, proximal arms, dorsal forearms, dorsal hands, and distal legs (Figures 1–3). Many lesions had central clearing with hypopigmented atrophic centers and raised peripheral borders, some beaded and some serpiginous (Figures 1–4). The absence of scale or other epidermal change was noted. The lesions were in a distinct photo-distrfibuted pattern on the neck and chest with obvious sparing of areas on her shoulders and chest covered by her sleeveless top, as well as the posterior portions of the neck covered by her hair (Figure 1). Photo-protected locations such as the buttocks, groin, breasts, abdomen, lower back, and axillae were also spared. In areas of high lesion burden such as the upper extremities, many plaques were observed to coalesce (Figures 2 and 4).

Figure 1.

Tetrad of clinical photographs demonstrating the striking photo-distribution of lesions on the upper chest (panel a), lateral face and neck (panels b–d), and upper back (panels b) with notable sparing of portions of her shoulders, lower chest, and neck covered by her tank top and hair (panels a–c). The lesions on the head and neck display distinct raised, serpiginous borders (panel d).

Figure 2.

Tetrad of clinical photographs in panels (a–d) showing numerous coalescing, erythematous plaques with central atrophy diffusely distributed on sun exposed areas of the bilateral upper extremities (dorsal forearms, bilateral proximal arm, and dorsal hands). Many plaques exhibit raised, serpiginous borders.

Figure 3.

Clinical photographs of the bilateral distal legs over the anterior tibial areas demonstrating large geographic plaques and scattered satellite papules with elevated erythematous borders and prominent hypopigmented atrophic centers. Panel (a) depicts the right leg and panel (b) depicts the left leg.

Figure 4.

Close-up clinical view illustrating coalescing plaques on the right dorsal forearm to demonstrate the prominent raised, erythematous borders and notable central clearing with hypopigmentation and atrophy characterizing the typical morphology of the majority of this patient’s lesions.

Punch biopsies of skin were obtained from the right shin, anterior base of neck, and right hand. On histology, all three specimens demonstrated granulomatous inflammation and scattered multinucleate giant cells, with some containing intracellular elastic fibers consistent with elastophagocytosis (Figures 5–7). Laboratory work-up revealed a negative anti-nuclear antibody, an elevated glucose of 188 on an otherwise normal complete metabolic panel, and a normal complete blood count with differential. Based on the clinical and histological findings and sun-exposed distribution of lesions, she was diagnosed with disseminated actinic granuloma.

Figure 5.

Punch biopsy of skin biopsy (hematoxylin and eosin stain, magnification 2×) showing diffuse dermal palisaded granulomatous inflammation with scattered multinucleate cells.

Figure 6.

Histopathologic image at higher magnification (hematoxylin and eosin stain, magnification 20×) showing numerous histiocytes and multinucleate cells, many of which contain intracellular elastic fibers consistent with elastophagocytosis.

Figure 7.

Elastin stain (Verhoeff–Van Gieson stain, magnification 20×) highlighting the intracellular elastic fibers within multinucleate cells, a phenomenon known as elastophagocytosis.

Due to her extensive disease and self-reported failure to improve with multiple prior treatments administered by an outside clinician, systemic treatment with hydroxychloroquine was advised. Surprisingly, the patient repeatedly declined treatment with this medication in part because of concern for serious side effects due to media coverage surrounding the inappropriate use of hydroxychloroquine for treatment of COVID-19 infections. Diligent sun protection measures and strict diabetic control were stressed to the patient. Because the patient preferred conservative management, topical betamethasone dipropionate 0.05% ointment applied twice daily for 3 weeks, followed by maintenance treatment with twice-daily topical tacrolimus 0.1% ointment, were initiated. However, she failed to show significant improvement with topical treatment. Months later, her primary care physician administered intramuscular triamcinolone to treat chronic bronchitis. After receiving systemic steroids, her skin lesions rapidly and completely cleared and have remained in remission with vigilant sun protection.

Discussion

Actinic granuloma was first described by O’Brien, who proposed that ultraviolet damage to dermal elastic fibers serves as an antigenic stimulus, triggering an autoimmune granulomatous inflammatory response.^2,5 This rare cutaneous process has a female predilection, typically presenting in middle-aged individuals as annular and polycyclic plaques in a photo-distribution.^6–8 Plaques expand centrifugally and characteristically develop hypopigmented, atrophic centers. ⁹ The pathogenesis of actinic granuloma is unknown, although it is hypothesized that ultraviolent light may lead to degeneration and antigenicity of dermal elastic fibers.^4,5 A related entity, AEGCG, first termed by Hanke et al., ³ presents with lesions of similar clinical and histologic appearance on photo-protected sites and may be associated with underlying diabetes mellitus.^4–6 On histopathology, both are characterized by granulomatous inflammation with elastophagocytosis, multinucleate giant cells, fragmentation of elastic fibers, and absence of necrobiosis or mucin deposition.^2,5,6,10 Given the shared histologic patterns and overlapping clinical morphology, these two entities likely represent a spectrum of the same disease. ⁴ While prior case reports describe localized actinic granuloma, Lazzarini et al. documented an “extensive” presentation with involvement of the face, scalp, and ears.^4–6,8,9 In contrast, the current report demonstrates an unusually widespread case of actinic granuloma with disseminated involvement of the face, neck, chest, upper back, arms, hands, and legs.

Although ideal treatment remains unclear, therapeutic options include topical, intralesional, and systemic corticosteroids, as well as cryotherapy, topical and oral retinoids, topical calcineurin inhibitors, tetracyclines, dapsone, antimalarials, adalimumab, immunosuppressants, and laser therapy.^4,7,11–21 While hydroxychloroquine has demonstrated efficacy in treating actinic granuloma in numerous reports; the patient described herein refused hydroxychloroquine treatment due to apprehension regarding adverse effects based on her perception of negative media coverage of the medication during the COVID-19 pandemic.^4,19–21 While concern for hydroxychloroquine shortages was reported in the rheumatologic literature early in the pandemic, little is written about sensationalism associated with hydroxychloroquine during the COVID-19 pandemic and its potential to affect patients’ future decision-making with respect to treatment with this drug for rheumatologic and dermatologic conditions. ²² As a result of the pandemic, clinicians may need to overcome this unexpected treatment barrier when prescribing hydroxychloroquine.

Actinic granuloma is a rare cutaneous granulomatous disease typically presenting with single or multiple annular erythematous or skin-colored plaques on sun-exposed skin. In this report, we demonstrate that actinic granuloma may also present with unusually extensive cutaneous involvement, underscoring the potential for a high lesional burden in a photo-distributed pattern, as in this case of disseminated actinic granuloma.