Herbert F. Haberman

NEUROTIC EXCORIATIONS: A REVIEW AND SOME NEW PERSPECTIVES

Neurotic excoriation is a commonly encountered dermatologic syndrome, which is usually associated with psychiatric pathology, most commonly obsessive-compulsive traits and depression. This disorder typically runs a chronic course. In addition to symptomatic dermatologic treatments for the self-inflicted excoriations and secondary pruritus, the treatment for this disorder is primarily psychiatric. In spite of this, neurotic excoriation has received little attention in the psychiatric literature, probably reflecting a lack of adequate collaboration between the dermatologist and the psychiatrist. This article critically reviews the literature on this disorder, and presents the salient features of five consecutive cases seen at the psychiatry-dermatology liaison clinic at our hospital. Possible etiology and treatment strategies in a previously unreported subgroup of patients with seemingly intractable symptoms are discussed. Further, the review highlights the fact that knowledge of this symptom complex is important for all psychiatrists, since it is frequently a “cutaneous sign” of psychopathology. N EUROTIC EXCORIATION is a disorder which has received little attention in the psychiatric literature. ’ It is a dermatologic syndrome where lesions are produced by the patient as a result of repetitive self-excoriations, in the absence of underlying physical pathology2 and usually in association with psychiatric pathology. *,* Unlike other self-inflicted dermatoses, such as dermatitis artefacta and malingering, the patients acknowledge the self-inflicted nature of their lesions. * The lesions vary in number, ranging from a few to several hundred. On occasion this syndrome has been associated with suicide .l In addition to topical dermatological preparations which are used for the symptomatic management of the self-inflicted cutaneous lesions and secondary pruritus, the treatment for this disorder is primarily psychiatric. In our experience at the psychiatry-dermatology liaison clinic, it is a relatively common disorder among both outpatients and inpatients. Therefore, further understanding of this disorder is important for the psychiatrist doing consultation work. Furthermore, the lesions are a “cutaneous sign” of psychopathology and knowledge of their existence can aid the overall assessment of any psychiatric patient. In this article, we present a review of the demographic and clinical features and treatments for this disorder and present the salient features of five consecutive cases seen at our clinic over a 3-month period. All patients presented with some consistent clinical features which have important treatment implications that have not been previously reported.

COMPARISON OF THE EFFECTS OF UV‐VISIBLE IRRADIATION OF MELANINS and MELANIN‐HEMATOPORPHYRIN COMPLEXES FROM HUMAN BLACK and RED HAIR

Clinical evidence indicates that people with light skin and red hair have a higher incidence of UV radiation‐induced diseases including cancer. It is not known whether this is because of the lower protection due to the smaller amounts of eumelanin present in the skin of these people or whether the presence of pheomelanin in their skin is responsible for the higher susceptibility to carcinogenesis. Irradiation of melanoproteins from red hair with UV‐visible light has been reported to produce superoxide. Comparative studies on the formation of superoxide during the irradiation of the melanins isolated from human black and red hair (BHM and RHM, respectively) are reported in this paper. These showed that no superoxide formation could be detected in the case of the BHM. whereas the formation of superoxide during the irradiation of RHM could be definitely demonstrated. Irradiation of the RHM with NADH resulted in the oxidation of more NADH than the irradiation of NADH with BHM. The observation that RHM is an active photosensitizer indicates that this property of pheomelanin present in light skin may at least partly be responsible for the harmful effect of radiation on people with light skin and/or red hair. Administration of hematoporphyrin followed by visible irradiation is a currently used mode of therapy for cancer. The present studies have shown that hematoporphyrin is bound to both BHM and RHM. The binding of hematoporphyrin to the melanins increased the formation of superoxide by RHM and the oxidation of NADH by both the melanins. The binding of porphyrins to melanins may have an influence upon the photosensitivity in diseases such as porphyrias and may also affect the therapeutic efficacy of hematoporphyrin.

Electron transfer properties of melanin.

Abstract Melanin synthesized from mushroom tyrosinase and 3,4-dihydroxyphenylalanine has been shown to oxidize NADH and NADPH, reduce ferricyanide, oxidized forms of cytochrome c and dichlorophenolindophenol, and catalyze the coupled oxidation of NADH and reduction of ferricyanide. Kinetic studies involving the determination of initial velocity at various concentrations of substrates and product inhibition measurements have been carried out on the NADH-ferricyanide-melanin reaction. The results are consistent with a ping-pong mechanism in which one product is formed prior to the reaction of melanin with the second substrate involving the reversible oxidation and reduction of melanin during the reaction. It may be concluded that melanin is capable of acting as an electron transfer agent in several reduction-oxidation systems.

Cutaneous Associations of Chronic Renal Failure and Dialysis

C renal failure (CRF) is associated with several dermatologic conditions. With better management, patients with CRF are living longer, and some of the cutaneous complications of CRF and dialysis are becoming more commonplace. Cutaneous changes associated with the following need to be considered: (1) drugs used to treat the underlying disease or manifestation of CRF; (2) CRF per se; (3) the treatment modality used in CRF, for example, hemodialysis or peritoneal dialysis; (4) renal transplantation, (5) primary disease process leading to CRF. This review is concerned with the first three categories. The cutaneous complications associated with renal transplantation are the subject of another paper; those associated with the primary disease process(es) leading to CRF have not been discussed. Table 1 lists the common causes of CRF in adults. Glomerulonephritis accounts for approximately 40% of the cases.

Oxidation of NADH by melanin and melanoproteins

Abstract The oxidation of NADH by melanin was employed as a means for studying the properties of melanin isolated from melanoma. The NADH-oxidizing activity of melanin isolated from B16 melanoma (tumour-melanin) was compared with that of the melanin synthesized by the action of monophenol monooxygenase (tyrosinase, EC 1.14.18.1) on 3,4-dihydroxyphenylalanine (dopa-melanin). Unlike dopa-melanin, the tumour-melanin did not oxidize NADH. When the proteins associated with the tumour-melanin were hydrolyzed by acid treatment, the resulting product readily oxidized NADH. Conversely, addition of bovine serum albumin to the melanin-synthesizing system or to the melanin already synthesized decreased the oxidation of NADH by the melanin. Similarly, polyarginine and polylysine decreased the NADH oxidizing activity while polyglutamate and polyaspartate did not have any effect. The results indicate that basic components of the proteins bound to melanin may be blocking the active sites of melanin involved in the oxidation of NADH. It is postulated that the electron transfer properties of melanin may be important in its protective role against radiation and toxic free radicals and that the inactive melanoprotein, as it occurs in the cell, may be converted to active melanin upon dissociation or degradation of the protein by agents such as irradiation.

MECHANISMS OF ACTION OF MELANINS

Melanin is a descriptive term (G. Melas — black), and is used to denote a number of compounds of varying chemical and physical properties and having a wide range of colours such as yellow, red, brown and black. Melanin is found at all phylogenetic levels, from the fungi to man. In the more complex organisms it occurs only in specialized cells and tissues. In man it is present in skin and hair, retinal pigment epithelium and irides of the eye, adrenal medulla, pineal body, substantia nigra of the brain, neutrophils, eosinophils, and possibly myocytes of the heart, hepatocytes and Kupffer cells of the liver (Blois, 1969; Edelstein, 1971; Lerner, 1974; Okun, Donnellan, Pearson & Edelstein, 1974; Van Woert, Prasad & Borg, 1967; Van Woert & Ambani, 1974). There are differences between the melanins present in various species, and even within a single species melanin in a particular tissue may be different from that in other tissues (Edelstein, 1971). Melanin absorbs light over a wide range of wavelengths. However, it has no distinct absorption bands in the ultraviolet, visible or near infrared regions. In the far infrared region there is a series of absorption bands which are quite similar in melanins of different sources, e.g. natural squid melanin, melanin from substantia nigra, as well as the melanins derived from different sources obtained by the autoxidation of dopa, L-adrenaline, tyramine, serotonin, dopamine, tryptamine, catechol, noradrenaline, and hydroquinone. These bands are however absent in some other black substances e.g. charcoal and graphite (Blois, 1969; Van Woert, Prasad & Borg, 1967). X-ray diffraction studies of natural melanins have revealed similar patterns in different melanins irrespective of the starting substance (Tathachari & Blois, 1969). The absorption spectra and X-ray diffraction data suggest that despite the differences in the physical and chemical properties of the various melanins, they show similarities. An important property of melanins is their characteristic electron spin resonance (E.S.R.) signals (Blois, Zahlan & Maling, 1964; Commoner, Townsend, & Pake, 1954; Grady & Borg, 1968; Mason, Ingram & Allen, i960; Van Woert, Prasad & Borg, 1967). Analysis of these E.S.R. signals has made important contributions to the knowledge of the chemical structure of melanin and may indicate various aspects of the mechanism of the role of melanin as a protective agent. Several difficulties are encountered in determining the chemical structures of melanins. The classical Raper-Mason pathway (Mason, 1959; Raper, 1928) for the synthesis of melanins had long been widely accepted. According to this pathway tyrosine is oxidized to 3,4-dihydroxyphenylalanine (dopa) which is oxidized to dopaquinone, both steps being catalyzed by the enzyme tyrosinase or dopa oxidase. By means of a series of non-enzymic reactions dopaquinone yields indole-5,6-quinone. Melanin was considered to be a homopolymer consisting of indole-5, 6-quinone units. However, the free radical properties of melanins and the analytical data from the chemical degradation of melanins do not support this rather simple structure for melanins. The new findings show that several intermediates mentioned in the Raper-Mason pathway, as well as derivatives of these compounds, are also incorporated into melanins. Thus the structure of melanin probably includes several types of bonds viz. carboncarbon, peroxide, ether, carbon-nitrogen etc. Since each of the polymers is polyfunctional, the melanin chain could be branched at any monomeric position and could also form a three-dimensional structure. Thus melanins probably consist of random structures (Blois, 1971; Nicolaus, 1968; Swan, 1973). It is generally accepted that the main function of cutaneous melanin is to protect tissues against acute and chronic changes due to ultraviolet radiation viz. sunburn, ageing and carcinogenesis. How-

A comparison of the phototoxicity of protoporphyrin, coproporphyrin and uroporphyrin using a cellular system in vitro

The photobiological effects of protoporphyrin (PP), coproporphyrin (CP) and uroporphyrin (UP) were investigated using an in vitro model. Suspensions of Ehrlich ascites carcinoma cells were labelled with 51Cr and irradiated in the presence of a wide range of concentrations of PP, CP and UP. It was found that PP was the most potent photosensitizer in this system; CP was less effective than PP and UP was the least potent. The cell lysis by CP was enhanced by superoxide dismutase (SOD) and inhibited by catalase; the lysis by UP was also inhibited by catalase; on the other hand, the lysis by PP was not affected by SOD or catalase. These indicate that the cell lysis by CP and UP was largely due to hydrogen peroxide produced from superoxide formed during the irradiation. The lysis produced by PP was not mediated by hydrogen peroxide. These differences in the mechanisms of the phototoxicity of the various porphyrins may have relevance in the etiology and treatment of the porphyrias.

Carbon dioxide laser-treatment of resistant verrucae vulgaris : Retrospective analysis

Background: Verrucae are a very common dermatological problem that can be both painful and bothersome to the individual as well as costly to the health care system. In some cases Verrucae can be notoriously resistant to therapy. Objective: To determine the cure rate, side effect profile, and overall satisfaction with CO2 laser treatment of recalcitrant Verrucae vulgaris. Methods: A retrospective survey was sent to over 200 patients who had resistant Verrucae vulgaris treated with the carbon dioxide laser at The Toronto Hospital (Western Division) from 1989 to 1994. Results: Ninety-two complete responses were received. The overall cure rate was 64.1% at 12 months. There was no significant difference in cure rates between single compared to multiple warts (p = .824 Fishers exact test). The duration of the wart being present showed no difference in cure rate (p = .801 Fishers exact test). The location of the wart also had no influence on the cure rate (p = .433 Fishers exact test). Overall, 71.7% of the patients were happy with the laser treatment and 85.7% would have it done again. Conclusion: The carbon dioxide laser is an effective treatment of resistant Verrucae vulgaris.

Quantitation of hydrogen peroxide formed during UV-visible irradiation of protoporphyrin, coproporphyrin and uroporphyrin

Free porphyrins are strong photosensitizers. Previously reported findings indicate that the in vitro cell lysis induced by irradiation in the presence of coproporphyrin (CP) and uroporphyrin (UP) is mediated by H2O2 and that induced by irradiation with protoporphyrin (PP) is not mediated by H2O2. In the present study the possible role of H2O2 in the porphyrin photosensitization was investigated by direct measurement of the H2O2 formed during the irradiation of PP, CP and UP. Our results show that the amount of H2O2 formed decreased in the following order: UP, CP, PP. The amounts of H2O2 formed during irradiation of CP and PP were approximately 86% and 38% respectively in comparison to the H2O2 formed during the irradiation of UP. The formation of H2O2 was inhibited by sodium azide, a strong quencher of singlet oxygen. These observations are in good agreement with the previous report that the in vitro photolysis of Ehrlich ascites carcinoma cells by UP and CP, but not that by PP, was inhibited by catalase and clinical findings with patients with erythropoietic protoporphyria (EPP) and porphyria cutanea tarda (PCT). The patients with EPP, where the photosensitivity is due to PP, respond well to beta-carotene while beta-carotene does not protect against the photosensitivity in PCT, in which case the photosensitivity is due to uroporphyrin.

A qualitative study of the melanins from blue and brown human eyes.

Abstract This investigation compares the physical and chemical properties of melanins isolated from the human Eye Bank eyes which were divided into two groups viz. blue and brown on the basis of the colour of the iris. The uveal tissues in each group were pooled and homogenized with water. The supernatants after removal of debris were mixed with equal volumes of 12 n -HCl. The mixture was refluxed for 48 hr. The protein-free melanin was washed with water and dried. The melanin from blue eyes had a bluish tinge and that from brown eyes was brown. There was no significant difference between the U.V.-vis spectra of the two melanins. The i.r. spectra showed a characteristic major band in the region of 1000/cm which was absent in dopa melanin. Both blue and brown eye melanins showed similar composition of C,H,N and S. Protoporphyrin, chlorpromazine and paraquat formed complexes with these melanins. Both melanins catalyzed a few oxidation-reduction reactions. No significant difference in their catalytic activity in the coupled oxidation of NADH and reduction of ferricyanide was observed. However, the brown melanin-protoporphyrin complex showed decreased activity in the oxidation-reduction reaction as compared with blue melanin complex. Our studies show that although they are similar in most respects there are some differences in the physical and chemical properties of melanins from the blue and brown eyes.