Confluent and Reticulated Papillomatosis (CRP) is a skin disorder that is benign but causes significant patient distress because of its disfiguring lesions. Conservative treatment is not usually successful or even acceptable. As a result, many types of treatment have been tried in order to evolve a useful regimen which will help the lesions heal and prevent scarring and recurrence.
Among most commonly used antibiotics, minocycline is found to achieve impressive results byinducing almost 100 percent remission in most patients with CRP, though its mechanism of action is still unknown. The recurrence rate is also low, and these episodes respond readily to the restarting of the medication. In fact, the effect of minocycline is so striking that it has been proposed as one of the diagnostic criteria for this condition. Oral doxycycline and tetracycline has also been used for this purpose.
Minocycline causes several side effects such as hypersensitivity reactions, drug-induced lupus reaction, pigmentation disorders, and hearing loss due to vestibular damage. These must be looked for and prevented if possible by meticulous follow-up for the duration of treatment. In pregnant women, minocycline should be replaced by another drug.
As a result, it is likely to be supplanted by azithromycin, which has fewer adverse effects and is required to be taken only three times a week. Other antibiotics used for this purpose include fusidic acid, the macrolides erythromycin and clarithromycin (which are tolerated in pregnancy and have much lower risk of adverse effects) and cefidinir. Which one is used should be determined by determining the sensitivity of the organism concerned, the adverse effects, and the cost of treatment.
The mechanism of action of the macrolides and the tetracyclines may be via their antibacterial and anti-inflammatory actions of these drugs. The tetracyclines inhibit many pro-inflammatory cellular enzymes and cytokines such as the metalloproteinases, TNF-α, IL-1β, and hydrolases. The macrolides, on the other hand, regulate immune activation via IL-8 suppression and preventing the neutrophil oxidative burst. As such, it is necessary for these drug categories to be prescribed at levels which allow them to have anti-inflammatory effects. It is therefore unclear that there is a bacterial etiology for this condition, rather than a disorder of inflammation.
Both systemic and topical antifungal agents have been used in CRP to tackle Malassezia furfur infection, which was once thought to be an etiological factor. One of the first preparations to be clinically successful was topical selenium sulfide. This patient, however, was negative for yeast growth, and therefore the resolution of disease may have been due to keratolysis rather than control of fungal infection.
Other topical antifungals used include ketoconazole, tolnaftate, and itraconazole. Though initial resolution occurred, recurrence was inevitable. Systemic ketoconazole use was associated with the risk of hepatotoxicity and death. Fortunately, better medications options are used today.
Retinoids are vitamin A derivatives which seem to be useful in reducing skin cell turnover, and in smoothing out a rough surface. Both topical retinoids (tretinoin) and systemic (isotretinoin) have been used. Though effective, the use of minocycline is currently preferred because of the lower incidence of severe side effects and, in particular, the lower teratogenic risk. Systemic retinoids are reserved for those with resistant lesions.
Calcipotriol cream is of use in CRP at least in some patients. Tazarotene, urea, tacrolimus, tacalcitol, and selenium sulphide have also been tried, with mixed results. On the other hand, topical treatment is difficult to apply in all involved areas, and may be best suited for limited application to small areas of relapse.
It is important to treat any underlying weight or hormonal disorder, such as ensuring weight loss by healthy and safe means.
CRP usually responds to minocycline and azithromycin as first-line drugs, with remission being sustained for years. Recurrences are more common in those treated with other agents, occurring in up to 15 percent of such patients. The best therapy for recurrent CRP is with minocycline or doxycycline, or repeating the drugs which produced initial remission, because these options produce a very high rate of clearing of CRP lesions.
Reviewed by Afsaneh Khetrapal BSc (Hons)