Chronic actinic dermatitis treated with cyclosporine-A

ARTICLE

A case of chronic actinic dermatitis treated with cyclosporine-A

The name chronic actinic dermatitis (CAD) was first proposed by Hawak and Magnus in 1979 [1] and then accepted to resolve the confusing terminology of chronic photodermatosis [2]. It includes a group of clinical manifestations like photosensitive eczema, photosensitivity dermatitis, persistent light reaction and actinic reticuloid [3].

CAD is characterized by an abnormal photosensitivity in the UVB and/or UVA spectrum and even in the visible light range; photo patch testing reveals positivity to one or more photosensitizers [2, 3]. The patients present recurrent eczematous episodes which mainly involve the photo exposed areas and last for months, or even years, despite the presumed removal of the photo allergen [4].

The choice of treatment is influenced by the degree of photosensitivity and its action spectrum. Identification and removal of the photohapten is important as is use of photo-protectors. The administration of potent systemic immunosoppressive drugs or PUVA-therapy are efficient treatments, but often result in only partial or temporary improvements [1, 3]. We report our experience of a case treated with cyclosporine-A (Cy-A).

Case report

A 69-year-old man had presented, for about 12 months, a reddish-brown erythema and shedding with thickened and hypo-elastic skin on the face, scalp, neck and on the back of the hands and forearms, accompanied by severe pruritus (Figs. 1 and 2).

The lesions were diffuse from the outset and initially were characterizated by erythema accompained by slight edema, vescicles and desquamation. Later the skin became more lichenified with acute relapses of edema and vesicles in summer.

Family history revealed nothing worthy of note either physiologically or pathologically. Hematochemical laboratory tests, including urine dosage for uroporfirine and coproporfirine, were within the normal range.

A markedly lowered minimal erythema dose (MED) was observed. It resulted 10 mJ/cm² for broadband UVB (normal values in our laboratory are 30-60 mJ/cm²). MED for long wave UVA (330-460 nm) resulted underdetermined at the dose of 10 J/cm² which is the normal value observed our laboratory.

We applied SIDAPA (Società Italiana Dermatologia Allergologica Professionale: Italian Society of Allergological, Professional and Environmental Dermatology) patch test series that resulted positive to fragrance mix. Patch test of the perfume series were applied and these resulted positive to isoeugenolo 1% (++). The photo patch tests were positive to fenotiazine 2% (++). However, these reactions were not relevant.

The histology evidenced spongiosis and hyperkeratosis orto and parakeratosis. The derma presented perivascular lymphocyte infiltrate, occasional neutrophils and eosinophils.

Initially the patient was treated with beta-carotene 50 mg/die and total protection sun filters. Moreover, all the necessary precautions were taken to avoid contact with those haptens that were positive to patch and photopatch tests. Still no significant improvements were obtained. Subsequently a therapy with Betametasone dysodium phosphate 4 mg/die was administered with symptomatic remission after 10 days treatment. Once the dose was reduced to 1 mg/die the lesions and pruritus reappeared. So, seeing that this treatment had failed, and in view of the fact that the patient tolerated steroid therapy badly and had no intention of resuming it, we proposed PUVA therapy but the patient refused it because he traveled to work and he could not attend the phototherapy service. Therefore we decided to begin treatment with Cy-A at the dose of 4.5 mg/kg/die. One week afterwards the clinical picture had improved. Having obtained the clinical resolution (Fig. 3) after one month's treatment, we progressively reduced Cy-A dosage in the months that followed. At the dose of 1 mg/kg/die a rapid worsening of the clinical manifestations and pruritus was observed. Therefore the drug dosage was readjusted starting again with a dose of 3 mg/kg/die and a new rapid improvement of the clinical picture was obtained. The dose was progressively reduced to 1.5 mg/kg/die and no relapses were observed. Every time the patient spontaneously reduced the dosage or suspended the therapy the manifestations reappeared, only to recede again when the dose of 1.5 mg/kg/die was resumed. Now, 3 years afterwards, he is still on treatment at the dose of 1.5 mg/kg/die with the result that he no longer suffers pruritus, his skin has maintained a normal look and he has been able to live normally even out in the open air.

Discussion

Although the pathogenetic mechanisms are still mostly unknown, it is hypothesized that the frequent relapses observed in CAD patients are due to the unperceived contact with the photosensitizing substance, or with a chemically similar substance (crossed photosensitivity), or else to the eventual persistence of micro-quantities of the substance on the skin [5-7]. Instead, other Authors claim that the interaction between the photo allergen and exposure to visible light range causes the mutation of an endogenous protein to such an extent as to render it immunogenic. Therefore the immune response would be contrasted by the components of the skin itself, which, due to the photo-exposure, modify their antigens [2, 4, 8, 9].

Numerous immunohistochemical studies have demonstrated the presence of an infiltrate of T helper lymphocytes, indicating a type IV (cell-mediated) response probably secondary to a genetically determined anomalous reactivity of the immunitary system [10, 11]. These pathogenetic hypotheses indicate the use of immunosuppressive drugs. One of the most efficient treatments is PUVA therapy, based on the inhibitory effect on Langherans cells and T lymphocytes. The oral administration of 2.5 mg/kg of azathioprine is another efficient treatment [2, 12]. This drug reduces the number of Langerhans cells and the number of suppressor T cells [2]. Azathioprina induces a serious mutagenic risk: it is metabolized into a purine analog that has the potential to be incorporated into DNA, thus causing chromosome breaks. Cy-A is a drug that has a specific antilymphomonocytic activity. It is able to reduce the Langerhans cells' capacity to present the antigen and, by blocking the synthesis of interferon alpha, to inhibit the expression of the adhesion molecules (ICAM1) by the keratinocytes and by the dendritic epidermal cells which present the antigen. Therefore it is able to regulate the traffic of the lymphocyte population in the dermis [13, 14].

In the literature there are some case reports of severe CAD treated with Cy-A at the dose of 4 mg/kg/die that responded excellently, but with relapses after treatment suspension during the summer period [3, 12]. Our case also confirms that the treatment must be continuous. Cy-A was not able to clear CAD but only to keep relapses under control at a low dosage, although this allowed the patient to be exposed to light normally. The necessity to control the clinical manifestations led us to submit the patient to a continuous treatment and for this reason we wonder whether it is correct to expose him to Cy-A side effects and to a prolonged use of the drug. So far our patient has tolerated the low dosage well and the monthly hematochemical tests have always remained within normal range. Cy-A is used successfully for many disorders and in many cases the treatments are continued for a long time. Its side effects, as well as its tolerability, are well known in patients forced to take the drug for very long periods [15, 16]. Therefore, considering that CAD is an invalidating condition and that it is often resistant to traditional treatments, we consider the therapeutic results obtained satisfactory in any case. In conclusion, we think we can propose the use of this drug as an alternative treatment to traditional therapies although the treatment has to continue for a long time.

Article accepted on 28/5/02

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