• 17
    Feb
  • Clinical Study of Porokeratosis Associated with Immunosuppressive Therapy: DISCUSSION

Porokeratosis

Although the mechanism linking immunosuppres- sion and PK remains unclear, there is growing evidence suggests that immunosuppression may give rise to a loss of immunosurveillance, which allows the proliferation of abnormal keratinocyte clones in PK lesions. This suggestion is supported by im- munohistochemical studies that revealed defective expressions of HLA-DR antigens by epidermal Langerhans cells in the lesions of PK. If this is the case, this could lead to the uninhibited expansion of mutant clones of epidermal keratinocytes, which corresponds with the clinical development of PK.

PK development after organ transplantation is by far the commonest type of immunosuppression- associated PK, and this is most common after renal transplantation. The delay between organ transplantation and the appearance of PK ranges from 4 months to 14 years according to published reports, with an average of 4~5 years. In the present study, the average delay was also 4.1 years. It has been reported that the incidence of PK after renal transplantation varies from 0.38% to 10.86%. Herranz et al mentioned that result discrepancies might be explained, in part, by the fact that the clinical picture of PK is easily overlooked by physicians. Immunosuppressant protocol differences might also explain these different incidences, though this suggestion is substantially unsupported 298 patients have undergone renal transplantation at our hospital over the past 6 years, and thus, we would estimate the incidence of PK to be approximately 3%. During this 6-year period, PK was constantly detected among renal transplant patients, and no significant changes were made to the im- munosuppressive regimens used.
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According to a study by Herranz et al, the most common clinical pattern of PK has mixed characteristics of PK Mibelli and the superficial disseminated forms, that is, a few stable, less prominent lesions were scattered over sun-exposed areas of limbs. However, the definition of ‘mixed characteristics’ is unclear, and thus, we were unable to determine this terms means that DSAP and PK Mibelli coexist. In the present study, three cases (cases 4, 8, and 9) of the 9 cases enrolled showed coexisting PK Mibelli and DSAP, which prevents our confirming the dominant clinical variant of PK after renal transplantation. Further studies are required to elucidate this issue.

The premalignant potential of PK in immuno- competent patients has been well documented, as squamous cell carcinoma, basal cell carcinoma, or Bowen’s disease arise in approximately 7% of reported cases. This high incidence is probably related to chromosomal instability in fibroblasts and to the existence of abnormal clones in the epidermis of lesions. Interestingly, the frequency of squamous cell carcinoma has been estimated to be 40 to 250 times higher in renal transplant recipients than in the general population18. In addition to immuno- suppressive agents, human papilloma virus infection and exposure to sunlight are risk factors of cutaneous squamous cell carcinoma in organ transplant recipients. Because squamous cell carcinoma is much more aggressive and more frequently metastasizes in transplant recipients than in the general population, PK development after renal transplantation must be carefully followed up. All of the patients in this study were followed-up for 1 to 5 years, but no malignant change was observed.
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Physical destruction of lesions by electrodessica- tion, cryotherapy, or carbon dioxide laser treatment is an effective therapy for PK, though these treatments have undesirable potentials for scarring and depigmentation. More superficial lesions may response temporarily to topical retinoids or photo- dynamic therapy, and imiquimod (Aldara®; 3M, Loughborough, UK) was recently reported to be an effective treatment for PK. However, in the present study, the single patient treated by imiqui- mod showed little improvement. Previous authors concur with the view that PK lesions in trans-planted patients should be treated to prevent the development of squamous cell carcinoma.

In conclusion, PK in renal transplant recipients can show coexistent clinical variants. Further studies on this topic are needed, and physicians should strive to avoid understanding PK in renal transplant recipients.

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