Traitements (pour les professionnels)

Treatment (For Professionals)

How is seborrheic keratosis amenable to treatment?

Here follows a description some of the available and tried treatments and then a criticism of the methodology of all applied treatments follows:

1. Actual Guidelines

According to Dubertret et al.( Thérapeutique dermatologique). the following treaments are recommended:

– Cryotherapy with liquid nitrogen {Kee, 1967} would be the treatment of first choice. The lesion is blanched one mm around the lesion and the cycle is repeated two or three times. The results following cryotherapy {Kee, 1967} depend on the vasculature of the lesion, its thickness and how long and how often the liquid nitrogen is applied. Complications include transient hypopigmentation with peripheral hyperpigmenation and rarely, the formation of a scar. Unfortunately, SKs tend to recur following cryotherapy.

– In second intention and if the lesions are of small size, curettage is recommended.

– Thirdly the topical application of trichloroacetic acid is recommended.

2. Surgical Treatment

In case of a diagnostic doubt, the lesion should be removed. Systematic shave biopsy is even advocated by some {Thomas, 2004}. Cryotherapy destroys SK lesions and thus renders histological interpretation impossible. Thomas et al. (2004) {Thomas, 2004} as well as other authors {Kwittken, 1981; Mikhail, 1982; Sloan, 1993; Yap, 1997} considers that melanomas can arise within clinical lesions resembling SK, and that a histological examination should be done for any SK lesion excised.

Additional procedures such as lasers with promising results have been tried.

Lasers, which take aim at blood vessels by coagulating them,  lead to exfoliation of the superficial part of warts {Jacobsen, 1997; Webster, 1995}. Some lasers take aim at the melanin {Anderson, 1994}. The pulsed dye laser doesn’t seem to work because of its small energetical fluence and insufficient deepness of penetration {Mehrabi, 2002}.

{Khatri, 2003}Nd-YAGlaser was applied on 363 benign and premalinant skin lesions on 27 patients, including SK with a complete clinical and histological resolution {Mehrabi, 2002}. Alexandrite laser take aim at melanin-containing keratinocytes {Anderson, 1994}. It penetrates sufficiently in depth and has enough energetical fluence. This laser doesn’t affect surrounding tissues. After having applied the laser, SKs blacken, become friable and fall off two weeks after treatment. Even though alexandrite lasers have been used on small melanocytic naevi without forming any scars, hypopigmentation is sometimes encountered. Moreover some SK tend to reappear two months after treatment.

3. Topical Treatment

The most seemingly promising topical treatment for SK tazarotene appears to be effective when applied twice daily at a concentration of 0,1%{Herron, 2004}.  In a group of 15 patients, clinical and histological improvement was demonstrated in seven patients. Let us note that a once daily application did not provoke any improvement. But tazarotene, a synthetic retinoid that binds to RXR nuclear receptors, is known for its irritating effects {Menter, 2000} and ten of the patients reported initial burning, pruritus and redness following tazarotene application. Nevertheless, none of the patients discontinued tazarotene because of its side effects.

Another interesting topical treatment is a chemical peel of trichloracetic acid with pressure applied on the treated zone. The study was done on 49 korean patients with a type IV or V phototype. Diappearance of lesions was obtained in 42 patients {Chun, 2004 #374}.

{Van Scott, 1989} Alpha-hydroxy acids (AHA) applied topically have been proposed as an alternative for treating SK. They act by reducing the thickness of the stratum corneum by reducing cell cohesion between the corneocytes, in other words, it induces epidermolysis. The topical is to be applied before curettage. The procedure is not suitable for thick, densely hyperkeratotic lesions because penetration proceeds too slowly and large hypertrophic dermal papillae make epidermal curettage cumbersome. It is to be noted that AHA are damaging to the skin by provoking epidermolysis and a careless application is dangerous especially when concentrations 25 to 40% are used. No study of any dimension to our knowledge has shown the efficiency of this treatment.

{Klaus, 1990}Topically, ammonium lactate has been applied in a double blind approach against its vehicle in 58 patients aged between 37 to 82 years. Only elevation of the SK showed a significant decrease with ammonium lactate treatment, the length, colour and surface characteristics showing no difference with the control group. Two of the 58 SKs disappeared.

Topically, derivatives of vitamin D are considered by some as ineffective. In one study {Herron, 2004}, the application, once daily of calcipotriene 0,005% ointment did not result in clinical improvement. A recent article demonstrates the oppostite. In a clinical study over 8 years of over 100 patients, derivatives of vitamin D (calcipotriol, tacalcitol, maxacalcitol) were applied on the skin for a duration of three months. Overall, over 30% of cases showed an improvement of over 80% of the initial volume (see table below). Maxacalcitol was the most effective with over around half of the cases showing improvement (Mitsuhashi). Tacalcitol was the least effective, the authors attribute that to the low doses employed (2 micrograms per gram). Although unpublished, the action of active forms of apoptosis would be through apoptosis (Mitsuhashi, Yamagata university). The lesions showed no local inflammation lnor systemic side effects (no eryrthema, pruritus nor oedema). Even lesions which didn’t diminish in volume (surface x height) diminished according to the patients in pigmentation.

Usage of active forms of vitamin D on SK (study from march 1996 to june 2004)(Adapted from Mitsuhashi)

Imiquimod 5% has been tried in a group of 15 patients but didn’t enable any clinical nor histological improvement {Herron, 2004}. Redness, burning, and ulceration in the treatment in five of the patients and all five patients discontinued topical imiquimod due to discomfort and ulceration persisting for more than one month.

4. Oral Treatment

One treatment tried is oral vitamin D (1,25 dihydroxyvitamin D3) {Asagami, 1996}. Two groups of patients, one with lesions over 1 cm (n=14), the other with lesions under 1 cm (n=37) were treated with 0,5 µg (15 patients) and 0,25 µg (36 patients) respectively, except for one patient with a lesion under 1cm of diameter who received a dose of 0,5 micrograms.

The patients with the strong 0,5 µg dosage replaced their lesions by extensive scarring, and thus no subsequent reapparition of the lesions.

34 of the patients with the 0,25 µg dose showed a disappearance of the lesions without scarring, but with an ultimate reapperance of the lesions.

In the 39 treated patients who had a histology compatible with irritated SK, the lesions disappeared.

In the Mitsuhashi group only 10 patients were treated with oral vitamin D, but without any effect. Perhaps the local skin concentrations were too low. This explains why they tried active forms of vitamin D topically (see above).

Vitamin D and retinoids act on specific nuclear receptors (VDR and RAR, respectively) which form heterocomplexes with the nuclear receptors RXR (Mangelsdorf 1995). No association of vitamin D and retinoids has been tried in SK. In vitro, prostatic cancer cells have been inhibited to proliferate.

EVALUATION OF PREVIOUS TREATMENT METHODOLOGY IN THE TOPICAL TREATMENT OF SK

These previous studies evaluate the efficiency of a topical treatment and sometimes compare the effect of different substances locally applied on the skin. What is never taken into account, is the clininical or histological features. What has been demonstrated previously is that smooth surfaced SK correspond to the RA histological type and that ruguous surfaces SK correspond to the AHCS histological type, which we all know has a thick stratum corneum. Conversely, the acanthotic, smooth surfaced SK has a stratum corneum comparable with normal skin. This suggests that  substances should be able to penetrate more easily in the latter histological type.

Previous studies on topical medication therefore do not compare different histological types of SK. They don’t systematically take the histological type into account either. According to the clinical.histological section, clinical presentations correspond to histological types. Any normal skin with an important stratum corneum will not enable topical medication, especially when hydrophobic to penetrate easily. The clinical presentation (enabling to guess the histological type) should be taken into account when applying topical treatment in future studies to evaluate the efficiency of a treatment per se and to be able to compare it with other treatments.

CONCLUSION

The weakness of previous studies of topical treatment is that they do not take into account clinical and/or histological features. This means that all seborrheic keratosis will react in the same way following treatment, which is false. A documented clinical evaluation is necessary before any trial is undertaken.

Finally, most treatments are destructive, but suitable if there is little diagnostic doubt. Cryotherapy and the more recently applied vitamin D seem adequate: the latter only if the histology enables a penetration of that  substance.

According to our study, seborrheic keratosis doesn’t necessarily seem to affect light phototypes. Therefore destructive treatment is suitable if there is no diagnostic doubt, but shave biopsy with histological is preferable in case of a diagnostic doubt with a melanocytic lesion. For diagnostic purposes as for therapeutical purposes histology types need not be 5 but should be diminished to two types, or three if clonal seborrheic keratosis should be considered. A first type should regroup the reticulate and acanthotic SK under reticulo-acanthotic SK (RA) and the other should be called acantho-hyperkeratotic SK (AHCS). The reason is that clinically the disgnosis of the histological type can be guessed and destructive therapy given with a good estimate of the penetrability of the substance. The second fact  is that such a reduction in three histological types will not alter the dedifferentiation with a melanocytic lesion. The differentiation between basal cell carcinoma and clonal type of SK is yet another histological problem.

Conservative treatment should also be applied to photoexposed light phototype patients where the possibility of a colliding basal cell carcinoma is prevalent.

Nevertheless, we do hope that a preventive treatment for seborrheic keratosis as well as its colliding elements will become available in the future, so that the only shave biopsy will be only necessary if a life threatening melanoma is suspected.

This advice is for informational purposes  only and does not replace therapeutic judgement done by a skin doctor.

Contributors:

Dr Christophe HSU – dermatologist. Geneva, Switzerland