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Actinic granuloma is a condition characterised, histologically, by a preponderance of giant cells in close relation with damaged elastic fibres and the absence of necrobiosis, lipid, mucin, and palisading of the granuloma.1 The term was coined in 1975 by O’Brien who described similar histological features in cutaneous lesions of patients with sun damaged skin.2 Actinic elastosis is the hallmark of pingueculae and has been noted in association with a granulomatous reaction in only one previous report.3
The paucity of reports ensures that the condition is under-recognised both clinically and pathologically. We describe a further case with the novel association of scleral thinning, and further review the literature with reference to pathogenesis, disease associations, treatment, and significance for both ophthalmologists and pathologists.
A 67 year old white woman presented to the ophthalmology department with a 3 week history of a painless, red right eye. She had no previous ophthalmic problems. Significant past medical history included treated pulmonary tuberculosis and a lumpectomy for breast carcinoma 10 years previously. She had no significant family history and otherwise was generally well.
Ocular examination demonstrated a 3 × 3 mm, raised, flesh coloured, vascularised lesion on the right nasal bulbar conjunctiva with an associated corneal dellen (Fig 1). Further scleral changes were observed circumferentially around the limbus under an apparently healthy conjunctiva (Fig 1, arrowhead).
Initial differential diagnosis was carcinoma in situ of the conjunctiva or metastasis from breast carcinoma, although the lesion was not clinically typical of either.
An excision biopsy was performed. During surgery the underlying sclera was noted to be degenerate with significant thinning.
Histology of the lesion demonstrated dysplasia within the squamous epithelium and prominent solar elastosis with a granulomatous response to degenerative elastic fibres. There was a lymphoplasmacytic infiltrate characteristic of an inflamed pinguecula with granulomatous features suggestive of actinic granuloma (Fig 2).
Investigations into the cause of the underlying focal scleral atrophy included full blood count, erythrocyte sedimentation rate, serum VDRL, serum complement, anti-ro and anti-la antibodies, and rheumatoid factor which were all within normal limits. A screening serum ANCA was weakly positive (1:20) but antimyeloperoxidase assays were negative.
Anterior segment ultrasonography was normal. Fluorescein angiography of the anterior segment demonstrated an evenly perfused iris, but a filling defect clearly delineated the atrophy and thinning at the lesion site. Our patient was subsequently treated with topical antibiotics and eye padding and responded favourably over several weeks with progressive epithelialisation over the excision defect (Fig 3). The scleral changes persisted after resolution of the epithelial defect (Fig 3, arrowhead).
O’Brien, in his original description of actinic granuloma, described the pathogenesis as a phenomenon of repair occurring in damaged connective tissue.2 This concept was disputed by Ragaz and Ackerman7 who believed that the granulomatous inflammation was not a response to degenerative elastotic fibres but that the lesions described by O’Brien represented variants of granuloma annulare, a disorder of skin and ocular adnexae.8,9 The existence of conjunctival actinic granulomas in isolation distinguishes this condition from granuloma annulare and implies that granuloma formation can occur in response to elastotic material. Furthermore, actinic granulomas are histologically distinct with prominent elastotic degeneration of connective tissue fibres, giant cells, and inconspicuous palisading of epithelioid histiocytes.
McGrae postulated that actinic granuloma represented a cell mediated immune response to weakly antigenic determinants on actinically altered elastotic fibres with a predominance of helper T cells in the lymphocytic infiltrate.1
More recently the association of temporal arteritis and actinic granulomas of the skin has been documented.10 It is hypothesised that actinic radiation selectively injures elastic tissue in the skin and its superficial arteries and this tissue may then become antigenic, with local, humoral, and systemic overtones.
It is reported that the serum of patients with untreated giant cell arteritis contains a significantly elevated level of an elastase in the form of matrix metalloproteinase 9 (MMP-9) and that this enzyme was found to be abundant in the vicinity of damaged temporal internal elastic laminae.11 Gillot et al12 observed that sera from 12 of 13 patients with untreated giant cell arteritis contained high levels of elastase derived elastin peptides and that the peptides were targeted by T lymphocytes such as appear in the actual lesions of actinic granuloma1 and giant cell arteritis.13 This mode of autoimmune reaction complies with the “danger” model of autoimmunity described by Matzinger and appraised by Larkin.14
Our case presented with the novel association of an underlying focal scleral atrophy. Negative investigations for scleritis would suggest that this feature may be an extension of the autoimmune process representative of actinic granuloma rather than an independent idiopathic scleritis.
It is interesting to note that all documented cases of actinic granuloma of the conjunctiva have occurred in females which would be supportive of an autoimmune pathogenesis. Clinically, the differential diagnosis of conjunctival actinic granuloma includes pingueculitis, Bowen’s disease, conjunctival naevus, granuloma annulare (pseudorheumatoid nodule), and episcleral rheumatoid nodule.
Pathologically, the differential diagnosis includes pingueculae, pingueculitis, infection—particularly fungal, parasitic, or mycobacterial—and foreign body reactions. However, there is no granulomatous reaction to the actinic elastosis in pingueculae. In fungal and parasitic lesions there is often a prominent eosinophilic infiltrate associated with the granulomas. Caseous necrosis is seen in mycobacterial infections. In difficult cases special stains may help. Polarised light microscopy rules out the presence of any birefringent material.
Actinic granuloma of the conjunctiva represents a distinct clinical, histopathological, and immunological entity. Its classic presentation over a short period of a few weeks and poor response to topical steroid treatment should aid the ophthalmologist in recognising this lesion. Of practical importance to the ophthalmic pathologist is recognition that the granulomatous inflammation may be associated with elastotic degeneration and does not necessarily imply the presence of a foreign body, fungal, or mycobacterial infection.