Extensive hypertrophic lupus erythematosus: atypical presentation.

Lupus erythematosus (LE) is a disease with a wide spectrum of cutaneous and systemic manifestations. Clinical features of patients with LE show a great variation, and for this reason it is difficult to develop a unifying concept of this disease. Our objective is to present a case of hypertrophic LE with atypical morphology and extensive involvement, who responded favorably to isotretinoin. Diagnosis of hypertrophic lupus erythematosus (HLE) was confirmed by characteristic histopathological findings. Combination therapy with isotretinoin and hydroxychloroquine resulted in flattening and repression of previously refractory skin lesions. Sometimes, HLE lesions may present a diagnostic and therapeutic dilemma. In long standing lesions, squamous cell carcinoma may arise. Therefore, HLE requires adequate therapy with clinical and histopathological follow up.

What was known?

1. Hypertrophic or verrucous DLE (hypertrophic LE) is a unique subset, in which unusual lesions occur.

2. Verrucous lesions, chronicity and resistance to treatment are hallmarks of the disease.

3. Hypertrophic lupus erythematosus with lesions limited to the extremities and face have been previously reported in literature.

Introduction

Lupus erythematosus (LE) is a disease with a wide spectrum of cutaneous and systemic manifestations and has been the subject of many studies over several decades. Clinical features of patients with cutaneous LE also show a great variation. Hypertrophic or verrucous DLE (hypertrophic LE) is a unique subset, in which unusual lesions occur. The thick, adherent scale is replaced by massive hyperkeratosis, and the lesions look like warts or squamous cell carcinomas. It was also described as verrucous lupus erythematosus or keratotic lupus erythematosus. Verrucous lesions, chronicity and resistance to treatment are hallmarks of the disease. Hypertrophic lupus erythematosus with lesions limited to the extremities and face have been previously reported in literature. We hereby describe a case with extensive involvement and disfigurement, which responded very well to isotretinoin and hydroxychloroquine.

Case Report

A 32-year-old farmer presented with itchy, pigmented and disfiguring lesions over face, trunk and limbs, since five years. Within two years of the appearance of facial lesions, he developed numerous lesions on trunk and extremities. He had used high-potency topical corticosteroids and various medications but with partial response. Partial disease control was achieved only by a combination of systemic prednisone with hydroxychloroquine, but he developed steroid psychosis and so prednisone was withdrawn. Due to the disfigurement, he stopped working and confined himself to his room. On examination, he had lesions spread over the entire skin surface with erythematous and violaceous scaly plaques on the face, trunk and extremities. Few areas also showed atrophy and hyperpigmentation at the margins. The extremities showed discrete verrucous plaques with surrounding hyperpigmentation [Figure 1]. Palms, soles, hair, nails and mucosa were normal. Systemic examination was unremarkable.

Figure 1

Pre-treatment picture showing erythematous and violaceous hyperkeratotic plaques on the trunk and verrucous plaques on arms

Histopathology from the extremities and trunk showed acanthosis, hyperkeratosis with focal parakeratosis and vacuolar interface changes. In the superficial and mid dermis, a moderately dense lymphocytic infiltrate was present, extending to and obliterating the dermoepidermal junction [Figure 2]. Laboratory evaluation revealed platelet counts of 90,000/ml with ESR 30mm, ANA was 1:160 and anti-ds DNA, anti-SSA and anti-SSB were negative.

Figure 2

Histopathology from lesions showing hyperkeratotic, pseudoepitheliomatous hyperplasia of the epidermis with interface and deep lymphocytic infiltration and hydropic degeneration of the basal keratinocytes. (H and E ×40, ×100)

The patient was diagnosed as hypertrophic DLE and started on hydroxychloroquine 400 mg and topical clobetasol propionate; however he did not respond and lesions kept increasing; so isotretinoin 40 mg/d was added. After 10 weeks, the plaques resolved with residual erythema, scarring and pigmentation [Figure 3]. The patient was continued on same therapy for another three months. Then, the dose of isotretinoin was reduced to 20 mg daily. The periodic check on liver function tests, lipid profile and complete blood count were normal. Platelet count was also in the normal range. After six months, isotretinoin was stopped. He had a relapse 2 months after stopping the therapy, and was restarted on isotretinoin and he is still continuing on maintenance dose of 20 mg isotretinoin daily.

Figure 3

Post treatment - clearance of lesions and healing with hypopigmentation and hyperpigmentation

Discussion

Hypertrophic discoid lupus erythematosus or verrucous lupus erythematosus is an uncommon subtype of chronic cutaneous lupus erythematosus. But it rarely can be seen in subacute cutaneous LE or even SLE. It was first described by Behcet[1] in 1942. It represents approximately 2% of chronic cutaneous LE. The morphology of the lesions varies from squamous violet and painful papules and blackish hyperkeratotic ulcers[2] to depigmented atrophic plaques on the back, hyperkeratotic papules on the upper extremities[3] and disseminated keratoacanthoma like papulonodular verrucous lesions.[4] These lesions may resemble hypertrophic psoriasis, lichen planus, verrucae, keratoacanthoma or squamous cell carcinoma.

Histopathology of hypertrophic LE include hyperkeratosis, acanthosis and papillomatosis, in addition to the classic features of LE such as vacuolar lichenoid dermatitis, basement membrane thickening, superficial and deep inflammatory cell infiltrate and increased dermal mucin deposition. Two distinct histologic variants of hypertrophic LE have been described; lichen planus-like and keratoacanthoma-like patterns.[45] Due to the presence of pseudocarcinomatous hyperplasia, the histopathologic differential diagnosis may include hypertrophic lichen planus, squamous cell carcinoma, keratoacanthoma, halogenoderma, atypical mycobacterial and deep fungal infections such as blastomycosis. Immunofluorescence of the papulo-nodular lesions shows the deposition of IgG and IgM in a globular pattern at the dermal-epidermal junction. Discontinuous deposition of these antibodies is also seen at the basement membrane zone.[45]

Chronicity, absence of regression, therapeutic failures and potential to develop malignancy are causes of concern. Squamous cell carcinoma may arise on long standing hypertrophic lupus erythematosus lesions. Therefore, these patients require clinical and histological follow up.[35]

Hypertrophic LE is difficult to treat and we need treatment that must take care of both, the specific inflammatory infiltrate as well as the hyperkeratosis, which are elicited by inflammatory T cells.[6-9] Acitretin, isotretinoin and combination therapy of isotretinoin with hydroxychloroquine have been used to treat resistant hypertrophic lupus erythematosus, but the response is usually short-lived and maintenance therapy is required. In our case, combination of isotretinoin with hydroxychloroquine proved highly effective and the hyperkeratotic plaques disappeared promptly within the first three months of treatment but the patient relapsed after stopping the therapy; so he was started on isotretinoin again. There were concerns about isotretinoin worsening the thrombocytopenia; however, throughout the study period his platelets remained within normal limits.[10]

Our case had extensive involvement, which has rarely been reported. The lesions were lichenoid on the trunk and verrucous on the extremities. ANA and histopathological features guided us to the diagnosis and then the treatment with isotretinoin helped patient in leading a normal life.

Hypertrophic LE is difficult to treat and the new treatment modalities like biologicals, thalidomide and immunomodulators like mycophenolate mofetil[9] are expensive, which many patients cannot afford. We had limited treatment options due to poor socioeconomic status of the patient; however, he responded very well to isotretinoin and we feel that isotretinoin can be considered as first line of treatment in patients with hypertrophic LE.

What is new?

1. We describe an uncommon clinical presentation with extensive involvement.

2. We have shown good response to treatment with isotretinoin and hydroxychloroquin in Hypertrophic DLE which is known to be resistant to most of the therapies.

3. We feel that isotretinoin can be considered as first line of treatment in patients with hypertrophic LE