Giuliano Brandozzi

Long-term experience with low-dose interferon-α and PUVA in the management of early mycosis fungoides

Abstract:  Objectives: Combined high‐dose Interferon‐α and psoralen plus ultraviolet A irradiation (PUVA) have been reported to be effective in the treatment of early mycosis fungoides (MF); however, our study is the first controlled prospective study in the literature exploring the activity and tolerability of the combination with low dosages and evaluating further clinical outcome of early‐MF patients. Methods: We carried out a multicentric prospective Phase II clinical study on 89 patients with early‐stage IA to IIA MF treated for 14 months with low‐dose IFN‐α2b (6–18 MU/wk) and PUVA. Treatment success was analysed in terms of freedom from treatment failure. Results and conclusions: Complete remission (CR) was achieved in 84% and an overall response rate in 98% of cases: six‐month CR was associated with a non‐confluent skin infiltrate at histology (P = 0.044) and 14‐month CR with high epidermal CD1a+ dendritic‐cell density (P = 0.030). The combination protocol was successfully tolerated and the most common reason of ‘failure’ was related to relapse and not to toxicity. Sustained remissions were achieved in 20% of patients. High CD8+ lymphoid T‐cell density was associated with a lower relapse rate (P = 0.002). We think that our combination therapy can be considered an alternative approach compared with other modalities. Good immunological host surveillance in the skin lesions seems to be an optimal basis for the therapeutic success.

Lichen striatus in adults and pimecrolimus: open, off‐label clinical study

Background  Lichen striatus is a well‐known, acquired, self‐healing, linear inflammatory dermatosis. Lichen striatus occurring in adults tends to be more extensive and itchy than in children, sometimes requiring symptomatic treatment. The therapeutic approach usually adopted is topical steroids, even though prolonged use may lead to several side‐effects, particularly cutaneous atrophy.

Atypical neurothekeoma: a new case and review of the literature

Background:  Neurothekeoma is a rare neoplasm ascribed into the broad category of benign peripheral nerve sheath tumors. The atypical cellular variant of this neoplasm, showing a peculiar histological pattern, has been very rarely reported in literature.

Results of a prospective phase II trial with oral low-dose bexarotene plus photochemotherapy (PUVA) in refractory and/or relapsed patients with mycosis fungoides

IntroductionBexarotene is a synthetic retinoid effective in early and advanced stages of mycosis fungoides (MF)/Sezary Syndrome (SS) both in monotherapy and combination schemes.ObjectivesWe aimed to assess disease response to low-dose bexarotene and PUVA in maintenance in refractory and/or resistant patients with early and advanced stage MF/SS.MethodsWe followed prospectively 21 patients (stages IB-IV): 15 with early stage MF and 6 with advanced disease. “Mini” and standard protocols were respectively applied to patients who failed PUVA or several systemic regimens. The dose of bexarotene and the administration of PUVA were titrated individually and tailored during induction and maintenance according to previous therapy, disease stage and toxicity. We evaluated overall response (OR) at the end of maintenance, safety and event-free survival (EFS).ResultsAfter induction phase, OR was 85.6%, higher in early MF (93.4%) than in advanced disease (66.6%). At the end of maintenance, OR was 76.2%, including 33.3% of CR. Median EFS for the whole group was 31 months. Bexarotene was well tolerated regarding the side effects, with prophylaxis and progressive drug increase in the induction phase of the protocol. Side effects were mainly of low and moderate grades.ConclusionsWe observed a favorable rate of therapeutic effects and few, generally mild, side effects with low doses of bexarotene combined with PUVA.

Normolipemic plane xanthomatosis with acute development preceding the clinical onset of rheumatoid arthritis

To the Editor, In December 2006 a 52 year-old woman was referred to our department because of the presence of asymptomatic, wide yellow plaques located on the upper and inferior eyelids bilaterally, and associated with a diffuse yellow discoloration of the nape and neck (Fig. 1A,B). Lesions had appeared 9 months before our clinical observation and rapidly extended over the affected area. Patient denied systemic symptoms including fever, sense of fatigue, loss of appetite, myalgias, weakness or loss of energy, symmetric joint stiffness or swelling of the hands and feet early in the morning. On physical examination no locoregional lymphoadenopathy or abdominal organomegaly were present. Several laboratory investigations were performed: hemoglobin, hematocrit, platelet count, liver and kidney functional tests, glucose, bilirubin, lactate dehydrogenase, total cholesterol (192 mg/dl) triglycerides (97 mg/dl), low-density lipoprotein (LDL) cholesterol (119 mg/dl), high-density lipoprotein (HDL) cholesterol (60 mg/dl), serum protein electrophoresis, C4, C1q, CH50 complement, and urinary Bence-Jones protein. All were within normal limits; only the erythrocyte sedimentation rate and C-reactive protein were moderately elevated. A variety of non-organ specific (Cryoglobulin, antineutrophil cytoplasmic antibodies (ANCA), extractable nuclear antigen antibodies (ENA), antinuclear antibodies (ANA), aPL, anti-DNA, anti-beta2glycoprotein, anti-keratin) and organ specific (antithyroid, anti-parathyroid glands, anti-adrenal cortex, anti-ovary, anti-pancreatic islet cells, anti-gastric parietal cells, anti-liver, antikidney) autoantibodies were tested, and all were found within normal levels except for the presence of low levels of anti-cyclic citrullinated peptide antibodies (110 U/ml). X-ray examination of the chest and joints of both hands showed no pathological findings, and also abdominal and pelvic ultrasonography were within normal limits. Histologic examination of a biopsy specimen, obtained from the affected area on the neck, revealed the presence of foamy cells with a diffuse pattern of distribution throughout the superficial and middermis, and a mild diffuse lympho-histiocytic infiltrate, while the overlying epidermis was completely spared (Fig. 2). Granulomas, Touton giant cells and necrobiotic areas were not detected. Clinical and histopathological findings were consistent with the diagnosis of normolipemic plane xanthomatosis. Owing to the acute onset of the cutaneous lesions, we decided on a ‘wait and see’ approach, asking the patient to come back after 6 months. Four months later, the patient was hospitalized in the rheumatological department due to morning occurrence of a symmetrical, bilateral, diffuse stiffness and swelling of metacarpophalangeal joints, lasting over 1 h. Routine hematological analyses, including lipid profile, still persisted within normal levels except for a marked elevation of serum levels of rheumatoid factor (850 IU/ml), anti-cyclic citrullinated peptide antibodies (235 U/ml), erythrocyte sedimentation rate for 1 h (71 mm) and C-reactive protein (2,3 mg/dl). Nuclear magnetic resonance (NMR) confirmed the clinical suspicion of rheumatoid arthritis (RA), showing symmetric synovitis, bone marrow edema and erosions of metacarpophalangeal joints. The patient was discharged with the diagnosis of RA, because