Oral Psoralen-UV-A for Systemic Scleroderma

Abstract

W e read with great interest the case report of Downs and Kennedy 1 about the successful treatment of intractable palmoplantar pruritus with ondansetron. Because of our continuous research on pruritus and the action of serotonin type 3 (5-HT3) receptor antagonists, we think that there are major points that should be clarified. First of all, palmoplantar pruritus is an unusual location and a descriptive term but is not a diagnostic and disease entity. This raises the question on the etiology of palmoplantar pruritus. According to the report, neurological examinations, including electroneurography and upper spine radiography, had not been performed. It is possible that the palmoplantar pruritus was caused by nerve compression, nerve alteration, or neuropathy. The report further lacks important information such as the occupation and hobbies of the patient, to rule out external factors. The medical history does not mention the patient's prior external medications. Elderly patients often use vasoactive emollients and ointments, especially after having experienced vein thrombosis. Such therapeutics, applied by the patients themselves, sometimes cause contact dermatitis, which the authors might see excluded by the lack of skin lesions and the corresponding histological findings. Furthermore, topical agents such as those containing, for example, capsaicin, can lead to various skin sensations without specific skin lesions and histological findings. Unfortunately, there are no data on allergological examinations such as atopy screening (except for total IgE levels) and epicutaneous tests. Neither histamine, eosinophilic cationic protein, serotonin, nor 5-hydroxyindolacetic acid had been measured as a standard parameter in the peripheral blood. It seems that the authors did not consider an adverse drug reaction in their differential diagnosis. Drug-induced itching is usually generalized, but localized varieties occur. 2 The authors mentioned that the patient's hands and feet appeared "healthy" so that "pruritus sine materia" would be the more appropriate term to characterize this type of pruritus. Altogether, we think that there are important data missing in this case report. The nature of substances that mediate cholestatic and uremic pruritus are not completely known. It needs to be clarified that the mechanisms of action leading to the clinically observed antipruritic effect of 5-HT3 receptor antagonists in these types of pruritus are not understood. The first case reports on the antipruritic effect of 5-HT3 receptor antagonists 3 encouraged us to investigate the antipruritic potency of a 5-HT3 receptor antagonist (tropisetron) under experimental conditions. In healthy volunteers, we could not verify an antipruritic effect of tropisetron on histamine-and serotonininduced itch under experimental conditions. 4 As our first results also pointed toward a major role of skin mast cells (which cannot be explained in more detail in this letter) we performed the same experimental design when skin mast cells were depleted before. ...

European Dermatology Forum S1‐guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes

“…In the early phase with limited or localized skin involvement, UVA1 or bath‐PUVA or oral PUVA should be considered. Similarly to the successful treatment of LS with UVA modalities, a number of uncontrolled studies have indicated a beneficial effect on fibrosis in SSc . However, controlled studies are still lacking.…”

UVA/UVA1 phototherapy and PUVA photochemotherapy in connective tissue diseases and related disorders: a research based review

“…The study included four women suffering from SSc receiving a PUVA protocol consisting of 0.5 to 4 J/cm 2 single dose UVA given three times a week for ten weeks and a mean cumulative dose of 70.5 J/cm 2 UVA. Even though posttherapeutic skin severity scores did not alter significantly, at least microscopic analysis of the histological skin scores of all patients revealed visible improvements [33]. The last case report appeared in 2003 discussing the use of PUVA bath in a young girl, proposing that PUVA bath could also be used in childhood [34].…”

Phototherapy in Scleroderma

“…No difference between the groupsNoEl-Mofty et al [51]Prospective uncontrolled study12MorpheaUVA20 J/cm 2 3 times a week4006 + weeks2090% cure of early lesions, 50% cure of “late” lesionsNoEl-Mofty et al [12]Prospective uncontrolled study11SclerodermaOral + topical PUVA, Narrowband UVBUnavailableUnavailableUnavailableMean 10Most lesions had a decreased dermal thickness on ultrasound at 12 weeksUnknownBuense et al [56]Prospective uncontrolled study12Systemic sclerosisPUVA, bath or oralUnavailableMedian cumulative exposure 68.25UnavailableMedian 24Improvement in 11 patientsNoUsmani et al [29]Prospective uncontrolled study4Localized sclerodermaPUVA cream4 times a week. Maximum single dose of 3.5 J/cm 2 89.5 (range 67.5–121)Unavailable30Decrease in dermal thickeningNoGrundmann-Kollmann et al [76]Prospective uncontrolled study4Systemic sclerosisPUVA oral3 times a week for 10 weeksMean of 70.5 (range 50.5–92.0)10 weeks30Improvement of skin, joint mobility, grip strength, and skin thickness in three of four patientsNoHofer and Soyer [77]Prospective uncontrolled study17Localized sclerodermaPUVA bath0.2–0.5 J/cm 2 up to 1.2–3.5 J/cm 2 per treatment. First 20 treatments 4 times a week,...…”