Giovanni Luigi Capella

Depression circumstantially related to the administration of finasteride for androgenetic alopecia

In this paper we report 19 patients (14 males, 5 females; mean age 28.16 years ± 7.68 SD) out of a series of 23 (17 males, 5 females) who developed a mood disturbance (moderate to severe depression) during treatment with finasteride, 1 mg/day orally, for androgenetic alopecia (Hamilton subtypes III–V; Ludwig subtypes I–II). Depression, which significatively impaired sociofamilial relations, sleep and eating behaviour, was associated to marked anxiety in some cases, developed after 9–19 weeks of treatment with finasteride, and promptly resolved after suspension of the drug. Two patients accepted reintroduction of the drug, and depression relapsed within 2 weeks. Depression as an adverse effect of finasteride has been reported only once. Further studies are needed to confirm our circumstantial observations, which are based on a retrospective series of patients.

INTRAMUSCULAR LOW DOSE ALPHA‐2B INTERFERON AND ETRETINATE FOR TREATMENT OF MYCOSIS FUNGOIDES

Background. Mycosis fungoides is a lymphoma of cutaneous origin characterized by a proliferation of cells with a T phenotype.

Sarcoidosis presenting as erythema annulare centrifugum

Erythema annulare centrifugum (EAC), a disease belonging to the poorly characterized category of ‘figurate erythemas’, has been associated with a variety of conditions, such as connective tissue diseases, infections, neoplasms and drug reactions. Here we report a case of EAC associated with sarcoidosis, the first case in the literature to our knowledge. EAC was the sole sign of the granulomatous disease process, which was diagnosed by means of appropriate investigations only after the patient reported the sudden resolution of a long‐standing sensitization to perfumes and parabens. Steroid treatment for sarcoidosis improved the patients condition, and restored the allergic response to these substances.

Complementary therapy for psoriasis

ABSTRACT: The authors provide some specifications regarding the correct terminology to be applied in the field of complementary medicine, and review and comment on several complementary treatments for psoriasis. Putative psychotherapeutic equivalents are kept distinct from treatments based on the surreptitious administration of physical or pharmacologic agents. Limits on the application of psychotherapeutic techniques are discussed. Risks inherent to complementary treatments (psychological derangements, moral subjugation, physical damage, economic exploitation) are underscored. The authors plead for the application of adequate scientific criticism in complementary medicine, but warn that any approach to the practice of medicine which is not disinterested and patient oriented—as the academic one should be—will be inappropriate, misleading, or even immoral. In the authors’ opinion, this could also apply to the evidence‐based medicine movement (often perceived as the archenemy of alternative medicine), should this movement be influenced by economical, political, or other nonmedical factors.

A controlled study of comparative efficacy of oral retinoids and topical betamethasone/salicylic acid for chronic hyperkeratotic palmoplantar dermatitis.

BACKGROUND: Chronic hyperkeratotic dermatitis of the palms and soles represents a severe multi‐etiological problem, too often faced with ineffective or tedious topical remedies. METHODS: A single‐blind, matched‐sample design investigation was carried out of 42 patients with chronic hyperkeratotic palmoplantar dermatitis, who were administered acitretin 25–50 mg/day for 1 month, which was controlled versus a conventional topical treatment (betamethasone/salicylic acid ointment). Therapeutic improvement was expressed with the reduction of severity score (expressed on a 0–10 scale). RESULTS: Acitretin was significantly better than the conventional treatment after 30 days (two sided p<0.0001). Moreover, improvement significantly persisted 5 months after suspension of acitretin (p<0.0001), while this was not the case after suspension of the control treatment (p=0.3019). Lesions improved more rapidly with acitretin than with the control treatment (p<0.0002). Some cases of loss of sensitization in patch‐test‐positive patients were observed. Side effects were minimal or absent, and patients expressed overtly their preference for acitretin treatment. CONCLUSION: After evaluating the former literature, the risks and the benefits, as well as the overt superiority of retinoid treatment, the authors conclude that acitretin should be considered a first choice treatment for this fastidious condition.

Psoriasis, lichen planus, and disorders of keratinization: unapproved treatments or indications1

What do we exactly mean by “unapproved treatments”? Do we refer to the fact that such treatments have not been approved by the FDA? Indeed, albeit highly authoritative, measures taken by this agency are in force only in the United States. Accordingly, to the authors of the present paper, who live and practice in Italy, “unapproved” could mean “straying from the guidelines recommended by the FTN” (the Italian Therapeutic Formulary). A tentative synonym for “unapproved treatments” could be “off-label prescriptions”1 (including use not exactly corresponding to recommendations by the manufacturer). This has the advantage of covering most prescriptions that follow at least some anecdotal source in the scientific literature; however, innovative or experimental therapies, as well as specific agents approved only in foreign countries, escape this definition. Indeed, we believe this nominalistic way of approach leads nowhere. The point is that many somehow accepted (“approved”) treatments are available for several conditions. Indeed, sometimes they do not work2 or cannot be performed. Moreover, the existence of unusual diseases is a fact. An acceptable operational definition of “unusual disease” could be the following one: It is so infrequent a disorder that it cannot be studied with case-control methodology in acceptable time because of case shortage or heterogeneity. The fact that randomized clinical trials cannot be always feasible2,3 must be accepted. Finally, medicine has not come to an end, and undescribed diseases still exist.4 According to this definition, it is not only seldom diagnosed or novel entities that are included in the group of unusual diseases. Indeed, patients with common diseases presenting in forms which are atypical, unresponsive to “approved treatments,” or in which “approved treatments,” albeit necessary, are contraindicated or unfeasible, must be regarded as people suffering from an unusual disorder (Fig 1); they deserve “unapproved treatments” as well. Otherwise such patients will be left at the mercy of their illnesses. We review here several unapproved treatments for the disorders listed in the title. Indeed, the reader must unceasingly bear in mind this methodological foreword to grasp the full meaning of our eclectic approach, which is expressly devoted to the special personalized management of that given a specific patient who is currently cared for. Skills, experience, creativity, as well as fortune5 are the mainstays of every “unapproved therapy.” Accordingly, even obsolete or retired drugs have been briefly quoted in the present review, because they offer the practical clinician an occasion to exercise his or her judgment in finding innovative therapies, which could also consist of rediscovered drugs.1 Why not?

Psoriasis and other papulosquamous diseases in infants and children

Many excellent textbooks on pediatric dermatology are available,2–8 and pediatric diseases are well covered even in many treatises of general dermatology. It would therefore seem useless endeavoring to repeat in a restricted space the matter which is put forth through thousands of printed pages. Accordingly, we will not reproduce here another picture of a “Typical case of PRP of the knee in a child aged . . . ” but we will survey critical items regarding diagnosis and choice of treatment of papulosquamous diseases in this peculiar age subset. This is not an article for beginners, and full knowledge of clinical dermatology is a prerequisite to study it with profit. However, it can also serve as a tool for training of residents in dermatology and clever medical students. Indeed, highlevel clinical practice leans on the same principles as chess mastery: under the guidance of a sound chess strategy, one must thoroughly analyze thousands of critical positions, grasp their deepest significance, and be ready to recollect each of them at the right time in order to exploit the acquired knowledge. Too often, this is called experience, but the choice of such a term sounds inappropriate, as “experience” bears the zest of quackery and of slapdash, parrot-fashion practice. Indeed, the right term is exercise, which must be either theoretical, so that you can diagnose diseases you have never seen before, because you have learned to recognize them, or practical, through engagement in clinical practice and merciless self-quizzing about difficult cases. Continuous meditation on roadmap articles (just like this one!) and book chapters is the bridge spanning the gap between the conceptual and the applied poles of knowledge. We hope such a dynamic approach will provide readers of Clinics in Dermatology with an openminded, flexible outlook on pediatric papulosquamous diseases, which is a sine qua non to broach the following items. In the past, the dermopediatric patient had been regarded as a “small adult with skin complaint,”5 and this concept was rightly blamed; however, the old misconception has been substituted by the commonplace notion that sick children are just something apart, quite unlike adults or elderly suffering from the very same disease. This puts pressure on clinical researchers who struggle to document the originality of skin pediatric diseases. The somewhat amusing result is that you can read chapters in renowned textbooks of pediatric dermatology describing the very adult pattern of a given illness, which then conclude with short notes on peculiar aspects of the child, or with clauses such as “The disease of children is the same as in adults,” “References about children are scarce,” and so on. Particularly in the case of papulosquamous diseases, such efforts are overtly artificial, because in general such diseases contribute to extending the category of “adult skin diseases in the pediatric patient” introduced by Howard and Tsuchiya.9 This article has been written by two clinical, general dermatologists who take care of pediatric patients among others in their daily office practice. The authors advocate that clinical dermatology is a very united corpus of compact doctrine, and that one cannot be a fine diagnostician and therapist of pediatric skin diseases if he or she has a sectorial and limited outlook on the discipline. The dermatologist who takes cares of children must also be a pediatric dermatologist, not solely a dermatologic pediatrician!

Alternating recombinant and natural alpha-interferon helps to prevent clinical resistance to interferon in cutaneous T-cell lymphoma treatment [12] (multiple letters)

Sir, (WellferonB , Glaxo-Wellcome), natural leukocyte (CilferonB , Janssen-Cilag) and raIFN (Intron-AB , Schering-Plough), 3 It is well known that prolonged administration of recombinant alpha interferon (raIFN) in several viral and malignant disMU intramuscularly, daily or on alternate days depending on the clinical outcome, evaluated as in our former paper (4). eases can be followed by loss of clinical activity of the drug. In the majority of these cases, the occurrence of insensitiveness Etretinate, 50 mg/day orally, is routinely coupled. After more than 3 years of experience, we have observed no loss of clinical to raIFN could depend on the synthesis of biologically active raIFN-neutralizing endogenous antibodies (1), although some effectiveness of IFNs in 7 of the 8 patients we have been treating. argue that a cause-and-effect relation between these facts has not been proven (2). Recently, others have pointed out that Formerly we predicted that alternative use of various kinds of IFNs could prove effective in treating lymphoproliferative even non-neutralizing IFN antibodies could be relevant in affecting alpha interferon efficacy (3). We started using alterndiseases of the skin selectively (4). On the ground of our satisfying pilot results we confirm our belief, and we encourage ate treatment with different interferons (IFNs) in 1994, when we observed our first case of resistance to raIFN in connection other groups to try such alternating protocols on extended series of CTCL patients in order to lay the groundwork for with the treatment of cutaneous T-cell lymphoma (CTCL). These are our pilot reports. controlled studies. Incidentally, we must unfortunately recognize that public health service officials are indifferent to, or even mistrustful of empirical therapeutic attempts, which are CASE REPORTS needed in the specialized management of rare conditions for Case 1 which codified therapy is unavailable or often ineffective. In A 44-year-old man with CTCL (Scandinavian MF group stage II ) Italy the use of natural IFNs is limited by bureaucratic and (4) had been treated with raIFN, 3 MU/day intramuscularly, and administrative restrictions, and special authorisations must be etretinate, 50 mg/day orally, according to the protocol described obtained. elsewhere for a former series of CTCL patients treated with IFN (4). Clinical resistance ensued 98 days after the beginning of the treatment. His condition deteriorated to stage III in a few days. Thus we decided REFERENCES to treat this patient with natural IFNs, as already done by other researchers in chronic myelogenous leukemia patients (5). In a fort1. Kuzel TM, Roenigk HH Jr, Samuelson E. Suppression of antinight the disease regressed to a stationary stage II, which has lasted interferon alpha-2a antibody formation in patients with mycosis for more than 3 years up to now. fungoides by exposure to long wave UV radiation in the A range and methoxsalen. J Natl Cancer Inst 1992; 84: 119–121. Cases 2 to 8 2. Steis RG, Smith JW, Urba WJ. Resistance to recombinant interFearing that other cases of resistance to raIFN could ensue, we feron alfa-2a in hairy-cell leukemia associated with neutralizing prophylactically turned the other patients currently treated with raIFN anti-interferon antibodies. N Engl J Med 1988; 318: 1409–1413. or newly enrolled (7 males; 5 stage II, 1 stage III, 1 stage IVa; mean 3. Rajan GP, Seifert B, Prümmer O, Joller-Jemelka HI, Burg G, age 57; range 42–74; mean disease duration 0.5 years) to alternating Dummer R. Incidence and in vivo relevance of anti-interferon IFNs. Partial remissions (4 cases) or reductions of progressive disease antibodies during treatment of low-grade cutaneous T-cell to a stable one (3 cases) were always obtained and maintained (range lymphomas with interferon-alpha-2a combined with acitretin or 9–32 months), except in the stage III case: he became insensitive to PUVA. Arch Dermatol Res 1996; 288: 534–548. IFNs in 1 month and had to be treated with total body electron beam 4. Altomare GF, Capella GL, Pigatto PD, Finzi AF. Intramuscular irradiation, which was successful. low dose alpha-2b interferon and etretinate for treatment of mycosis fungoides. Int J Dermatol 1993; 32: 138–141. 5. Von Wussow P, Jakschies D, Freund H. Treatment of anti rIFN DISCUSSION alpha 2 antibody positive CML patients with natural interferon When we decided to put the first patient of our series on alpha. J Interferon Res 1989; 9 (Suppl 2): S113 (Abstract). 6. Galton J, Finter N, Nethersell A. Low incidence of neutralizing alternating IFNs, we had considered the fact that the developantibodies in patients treated with human lymphoblastoid interment of antibodies to natural IFNs presented with a lower feron (IFN-alfaN1). J Interferon Res 1989; 9 (Suppl 2): S128 incidence and seemed to induce loss of clinical responsiveness (Abstract). less frequently (6). Moreover, it had already been stated that 7. Dianzani F, Antonelli P, Amicucci P. Low incidence of neutralizing in many instances therapeutic efficacy could be re-established antibody formation to interferon-alfa 2b in human recipients. by resuming treatment with natural alpha-IFN (7). These J Interferon Res 1989; 9 (Suppl 1): S33–36. facts opened up the outlook of administration of various IFN mixtures in rotation to CTCL patients. Our results were quite encouraging; thus we extended the rotation administration of Accepted October 1, 1997. IFNs to all of our CTCL patients currently treated with raIFN, without expecting the clinical onset of resistance to a Gianfranco Altomare, Giovanni Luigi Capella and Elena Frigerio given IFN. The ‘‘rotation protocol’’ we now follow consists Istituto di Dermatologia dell’Università, Ospedale Maggiore IRCCS, Via Pace 9, I-20122 Milan, Italy. of alternating 3-month cycles of natural lymphoblastoid

DENSITOMETRY OF PAUTRIER'S MICROABSCESS CELLS IN CUTANEOUS T CELL LYMPHOMA

Background. Epidermotropic lymphoid T cell infiltrates are part of a continuous spectrum of lesions ranging from “benign” parapsoriasis to frank cutaneous T cell lymphoma (CTCL, mycosis fungoides). Either the clinical or histologic differentiation between these entities prove often difficult and the prognosis may be difficult to assess.