Giuseppe Hautmann

Neuropeptides in skin

Neuropeptides are a heterogeneous group of more than 50 molecules that play a role in various cutaneous functions and diseases; they act as neuromodulators, neurotransmitters, neurohormones, and hormones. In the skin, neuropeptides are synthesized locally (i.e., in keratinocytes and in endothelial cells) and are transported by nerve fibers or immune cells (i.e., lymphocytes, monocytes, and polymorphonuclear cells). Specific receptors and binding sites for neuropeptides have been described in different cell lines in the skin (keratinocytes, endothelial cells, immune cells, fibroblasts). Many different biologic actions of neuropeptides have been demonstrated. Depletion of cutaneous neuropeptides (i.e., with capsaicin cream) or therapeutic use of neuropeptide agonists and/or antagonists may aid in the treatment of skin diseases.

Cigarette smoking, wound healing, and face-lift

Cigarette smoking is one of the major health problems in Western countries and is the single most preventable cause of death and disease in the United States.1 More than 30% of cancer-related deaths are due to tobacco use.2 Worldwide, tobacco is estimated to be responsible for approximately 3 million deaths yearly.3 Cigarette smoke contains over 1500 different components that have wide-ranging pharmacological effects on a variety of tissues in the body.4 The harmful effects of direct exposure to the components of cigarette smoke include an increased risk for developing oropharyngeal and lung cancers and chronic obstructive pulmonary disease.5,6 Detrimental effects of cigarette smoke at sites remote from direct exposure include an increased risk for cancer of the urinary bladder and acute myocardial infarction. These findings suggest that the toxic products of cigarette smoke also act through indirect exposure of the target organ.7 New data make smoking particularly relevant to dermatologic patients. Knowledge of the cutaneous effects of smoking is important because it provides another tool for counseling patients on the dangers of smoking. Moreover, it may provide some patients with an effective motivation to quite smoking, especially those who may be more concerned about their outward appearance than about the potential internal damage associated with smoking.8

The many faces of cutaneous vasculitis

V asculitis is a general term that refers to segmental, angiocentric inflammation and damage to the blood vessel walls.1 This term does not specify the type of inflammation, nor the size of the vessel involved in the skin, an organ that is well supplied with vasculature and frequently develops different manifestations of vasculitis.2 Often, the skin apparently serves as the initial organ upon which vasculitis is manifest, with involvement of the small to mediumsized vessels that supply nutrients to the skin itself. Although there are times when the only recognizable organ system involved is the skin, cutaneous vasculitis represents a systemic disease process that in many cases is linked to the presence of circulating or locally formed immune complexes (CIC), or may occur through different direct vessel-based immunologic or nonimmunologic mechanisms.

Non-tuberculous mycobacterial skin infections

General description The mycobacteria are a large genus which includes important pathogens of man and other vertebrates, apparently harmless commensals, and free‐living saprophytes. The relative importance of non‐tuberculous mycobacterial diseases has been undergoing evolution during the past few years and further changes and modifications are expected to occur in the near future. In this paper we review the microbiological, clinical, histological and therapeutical aspects of the most important human pathogens of non–tuberculous mycobacteria.

Psychoactive drugs and skin

In this issue you will find a paper written by Baba et al. (pp. 399–401) about anticonvulsant hypersensitivity syndrome. This is a rare, potentially life-threatening complication of antiepileptic medications. It is most often caused by aromatic anticonvulsants such as phenytoin, phenobarbital and carbamazepine, 1 but can also occur with non-aromatic anticonvulsants such as lamo-trigine, or other drugs, including sulphonamides, dapsone, minocycline, azathioprine, allopurinol, terbinafine and more. 2 The rate of occurrence is from 1 in 1000 to 1 in 10 000 in cases of exposure to the abovementioned drugs. 1 It is most likely to occur 2–6 weeks after the antiepileptic drug therapy is initiated, but can occur at any time. The tendency to develop the syndrome is familial 3 but a single genetic defect has not been identified. 4 It is recognized by the following triad of symptoms: fever, rash and lymhadenopathy, usually accompanied by internal organ involvement, 2 as you can read in the paper by Baba et al. Adverse cutaneous reactions (ACRs) to psychotropic medications occur regularly, are often easily noticeable and are potentially serious, so both dermatologists and psychiatrists should be familiar with the most common and life-threatening ones. Moreover, because ACRs may cause distress to patients and lead to non-compliance, physicians should also be aware of the benign and less common ones. Although the exact incidence of ACRs to particular medications is unknown and difficult to establish, it has been estimated that approximately 2–5% of patients taking psychotropic medications will develop an ACR, and that ACRs remain the most common allergic reaction to these medications. 5,6 This compares with an overall ACR rate of 2% among inpatients taking a variety of medications. 7 Among psychotropic medications, carbamazepine is associated with a uniquely high rate of ACRs (10–11%). 8,9

VULVITIS CIRCUMSCRIPTA PLASMACELLULARIS

A 56‐year‐old woman reported that an erythematous lesion, accompanied by severe burning, had appeared on the left labium minus about 2 years earlier. She had treated herself with topical deoxymethasone and estrogen topical medications that temporarily relieved the subjective synnptoms, but did little to help the clinical manifestations. The patients history revealed an adnexectomy and ovariectomy at age 40 after an ectopic pregnancy and a left saphenectomy for ectatic varicose veins at age 54.

The etiology of cutaneous necrotizing vasculitis

Vasculitis is a multisystem disorder with frequent involvement of the skin. Understanding of the vasculitides has been difficult, owing to their many manifestations and the multitude of classifications that have been proposed. Part of the problem relates to descriptions by subspecialists, each with his or her own bias. In 1952, Zeek offered a classification of vasculitis that, with modifications, is still the one mainly used today. Nevertheless, it is important to subclassify patients because of possible differences in etiopathogenesis, prognosis, associations with specific diseases, involvement in a certain organ, or therapeutic approach. Most of these differences are not actually acknowledged by these classification systems.1 A method of subclassifying these disorders separates the diseases by vessel size. Capillaries are involved in capillaritis. Small vessels, usually the postcapillary venule, are involved in what is traditionally known as leukocytoclastic vasculitis (LCV). Small arteries or arterioles can be involved in the panniculitides or polyarteritis nodosa (PAN). Medium-sized arteries are involved, particularly, near their bifurcations, in PAN, and in the granulomatous vasculitides. Large vessels are involved in giant-cell arteritis and its variants. It is absolutely necessary to perform a thorough systematic evaluation in patients with cutaneous disease as a manifestation of vasculitis to offer reliable prognostic advice to the patient. The pitfalls of viewing a multisystem disorder through a specialist’s eye are self-evident. Also, the problems of meaningful labeling and classification arise. Usually, the label polyarteritis nodosa (PAN) implies a poorer prognosis than does that of cutaneous LCV; however, as stated earlier and illustrated in the following discussions, these subclassifications are less than perfect. Our proposed variation of these classification2–4 may simplify and offer meaningful prognostication. We would divide these entities into those characterized by small-vessel and large-vessel vasculitides. The traditional LCV, which can be caused by unknown factors (idiopathic), infections, drugs, abnormal proteins, or an associated systemic disease, is within the small-vessel vasculitis category. To prognosticate within this group of patients, it is important to define the presence and type of systemic involvement. Large-vessel vasculitis includes PAN, granulomatous vasculitides, and giantcell arteritis. Affected patients generally have systemic disease, but they can also have cutaneous diseases. The cutaneous lesions can consist of those typical LCV, but ulceration, ischemic changes, necrosis, and livedo reticularis may be common. Strong experimental and clinical evidence suggests that cutaneous LCV is an immune complex disease (type III hypersensitivity reaction). Although multiple causes or associated conditions are possible and there are many clinical expressions, the linkage between the injury (cause) and the manifestation is probably an immune complex disease that leads to the inflammatory reaction.2–4 Figure 1 is a schematic representation of the pathogenesis of LCV. After antigenic exposure, soluble antigen-antibody complexes (circulating immune complexes, CIC) are formed. In the presence of antigen excess, these complexes can precipitate in the vessel wall. Following the deposition of the CIC, a complex series of events is initiated, ultimately leading to vessel wall damage, leakage of fluid (urticarial lesions), leakage of red blood cells (purpura), and ischemia (necrosis or ulceration).2–4 In addition to the immunologic events, several nonimmunologic factors may play a role in disease expression. Vasoactive amines, in particular endogenous histamine, can precipitate the deposition of CIC. This can be exploited clinically as a test for studying immune reactant deposits in lesional skin. Endothelial cells also appear to be primarily involved. These cells may produce and release cytokines that enhance the inflammatory response. Finally, local factors, such as anatomic location and viscosity, may help explain the clinical manifestations of a given vasculitic syndrome. Multiple etiologic agents have been implicated in the various vasculitic syndromes. Etiologic factors or associated conditions are similar for all the syndromes and From the Department of Dermatology, University of Florence, Florence, Italy. Address correspondence to Grazia Campanile, M.D., Department of Dermatology, University of Florence, Via degli Alfani, 37, 50121, Florence, Italy.

Unusual employ of laser in dermatology: to know, to be able to do, to be

We have read with great interest the paper by Kayako Hira on the case of chromomycosis treated with a combination of carbon dioxide laser and topical heat therapy. This report represents the second case of chromomycosis successfully treated by laser therapy. Thus, in our opinion, we really think that the paper should be kept in mind of dermatologists. Nevertheless, after we had studied this paper we have also made some considerations about the case, the lasers and more generally, on the risks of scientific research. We hope that the authors of the paper and our researchers will enjoy the comments.

The spectrum of plasminogen activator-dependent fibrinolysis-altered psychoinduced vasopermeability syndrome.

The word stigma comes from the Latin for “mark” or “brand,” which in turn comes from the Greek for “to tattoo.” The dictionary defines stigma (plural, stigmata) as a scar left by a hot iron, a mark of shame or discredit, an identifying mark or characteristic (as in a specific diagnostic sign of a disease), and bodily marks or pains resembling the wounds of the Crucified Christ and sometimes accompanying religious ecstasy. We focus on the latter definition although sometimes nineteenth-century dermatologists used the word to describe even a “minute” flat, red spot on the skin, the tiniest in the continuum of focal cutaneous vascular ectasias. In Rook and Wilkinson’s textbook the phenomenon of stigmatization is referred to only in the paragraph on hematohidrosis, defined as the bloody sweat “from the skin of the palms and elsewhere,” but “not related to sweat gland activity.”1