tretinoin and Arthritis--Psoriatic

Retinoids derived from retinol or beta-carotene are inactivated, among other ways, by enzymes belonging to the P450 cytochrome group. Liarozole, an imidazole-containing compound, is known to be a potent inhibitor of the cytochrome P450-mediated metabolism of all-trans retinoic acid. As a result, increased levels of this retinoid are found in skin and plasma. Therefore, in the treatment of psoriasis, therapeutic effects may be expected with liarozole which are similar to those observed with synthetic retinoids. In an open study, oral liarozole was given at a daily dose of 75 mg b.i.d., for 12 weeks to 31 patients with severe psoriasis. After 1 month, this dosage could be increased to 150 mg b.i.d. if there was no improvement or only moderate improvement. Initially, the effect of liarozole was mainly on scaling. A decrease in the Psoriasis Area and Severity Index (PASI) score of 45% at week 4, of 69% at week 8 and of 77% at week 12 was obtained, compared with baseline. A further decrease in the PASI score of up to 87% was observed in the 16 patients who were allowed to continue treatment for a maximum period of 12 months. An excellent or good improvement was noted in 77% of the patients within 12 weeks of starting treatment. This response rate had increased to 88% by the last follow-up visit. Nearly all patients (29 of 31) experienced adverse reactions, such as dry oral mucosa, headache and itching. These were mostly mild and transient, but four patients dropped out of the study because of an adverse event. Haematological, biochemical and cardiovascular parameters were not significantly influenced by liarozole. Six patients showed an increase in triglycerides, which normalized in three of four patients during further treatment. The results of this pilot study suggest that, at doses of 75-150 mg b.i.d., liarozole is an active antipsoriatic drug, and may be a useful addition to the existing therapeutic armamentarium. Controlled studies should be performed to compare liarozole with standard oral treatments.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites; Arthritis, Psoriatic; Female; Humans; Imidazoles; Male; Middle Aged; Psoriasis; Severity of Illness Index; Treatment Outcome; Tretinoin

Granulocytic sarcoma (GS) is a localized tumor composed of immature myeloid cells. This extramedullary tumor can present before, concurrent with or after the diagnosis of acute myeloid leukemia. GS is extremely uncommon in acute promyelocytic leukemia (APL). As a proportion of patients never develop systemic disease, correct and timely diagnosis may be rather difficult, but is a prerequisite for optimal outcome. GS should be considered in the differential diagnosis of children with unusual bone lesions. We describe a patient with GS who presented with symptoms mimicking osteomyelytis or rheumatoid disease.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Arthritis, Psoriatic; Biomarkers, Tumor; Diagnostic Errors; Female; Humans; Leukemia, Promyelocytic, Acute; Oncogene Proteins, Fusion; Osteolysis; Osteomyelitis; Remission Induction; Sarcoma, Myeloid; Shoulder Pain; Tretinoin

Superoxide dismutases' (SODs) expression is altered in several diseases including Alzheimer, atherosclerosis, cancer and psoriasis. Previously, we reported a marked increase in Mn-SOD and Cu,Zn-SOD functional activity in human dermal psoriatic fibroblasts. As retinoic acid (RA) has been used in the treatment of psoriasis and a mechanism for its beneficial effects is not understood, we investigated the effects of RA on SOD mRNA and protein expression levels in human normal and psoriatic fibroblasts. Prior to RA exposure, Cu,Zn-SOD protein and mRNA levels were similar in normal compared to psoriatic fibroblasts while Mn-SOD protein and mRNA levels were increased in psoriatic cells. However, in contrast to normal fibroblasts, exposure of psoriatic fibroblasts to 1 microM RA down-regulated Mn-SOD mRNA, and also decreased Mn-SOD activity by approximately 80% with no change in Mn-SOD protein levels. In contrast, Cu,Zn-SOD protein and enzymatic activity were modestly reduced by RA treatment in both normal and psoriatic fibroblasts. Furthermore, RA treatment of psoriatic fibroblasts also caused a decrease in Cu,Zn-SOD steady-state mRNA levels. These results indicate that RA can serve as a regulatory agent to down-regulate the steady-state levels of both Mn-SOD and Cu,Zn-SOD in psoriatic cells. These findings offer a new model for the antiinflammatory activity of RA when used in the treatment of psoriasis.

Topics: Arthritis, Psoriatic; Cells, Cultured; Female; Fibroblasts; Gene Expression Regulation, Enzymologic; Humans; Male; RNA Stability; RNA, Messenger; Superoxide Dismutase; Time Factors; Tretinoin