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We present seven immunocompetent patients devoid of any comorbidities and risk factors, who developed for the first time in their life varicella-zoster virus (VZV) reactivation shortly after 1st (four patients) and 2nd dose (three patients) of mRNA COVID-19 vaccines.All four patients who exhibited herpes zoster after the 1st dose of vaccine received the 2nd dose without any adverse reactions or complications. Oral treatment prescribed to all patients with valacyclovir (Valtrex 1 mg tds/day) for 5-7 days led to a complete resolution of symptoms, and rashes disappeared within 9-14 days. Presently, All patients have completed a 3-4½-month follow-up without any evidence of complications and/or recurrence of herpes zoster. (

Galectin 3 is a unique ~31 kDa protein that recognizes the N-acetyl-lactosamine structure of several glycoconjugates. It mainly occurs in epithelial and myeloid cells, but is also found in a variety of human cell types. In view of the crucial role played by galectin 3 in the regulation of cellular processes of essential importance and in the pathogenetic mechanisms of diverse disorders, it is not surprising that, particularly in the last three decades, the attention of the scientific community has been increasingly drawn to this extraordinary and multifunctional galectin. In this paper the authors summarize current knowledge on the expression of galectin 3 in normal and diseased human skin, its implications in the pathogenesis, diagnosis and prognosis of cutaneous disorders, and the perspectives of a novel approach to the treatment of the latter using galectin 3 or its inhibitors/antagonists.

In an attempt to raise awareness among physicians of the importance of early diagnosis and treatment of penile cancer and its precursor lesions, we report the unique case of a male patient with condylomata acuminata, Bowenoid papulosis, and squamous cell carcinoma, all HPV 16/18-positive, coexisting in his genital area.

Introduction Galectins constitute a phylogenetically conserved family of proteins with high binding affinity for glycoconjugates bearing β-galactoside residues. Surprisingly, knowledge of the expression pattern of galectins during human epidermal morphogenesis is very limited. Methods Fifty-eight biopsy skin specimens obtained from human embryos and 10 biopsy specimens obtained from healthy adult volunteers were processed for immunohistochemistry using a panel of antibodies against galectins 1, 3, 7, and 9. Results Fetal human epidermis was devoid of any galectin 1 immunoreactivity, whereas clear-cut changes were found in the galectin 3 immunoreactivity of fetal epidermis with advancing gestational age. The expression pattern of galectins 7 and 9 remained constant at all stages of gestation. Conclusions The changes in galectin 3 immunoreactivity of human fetal epidermis with advancing gestational age, which are reported here for the first time, suggest that this galectin and its ligands may be implicated in the molecular events underlying human epidermal morphogenesis. It remains to be elucidated in future investigations whether the expression pattern of galectins, particularly that of galectin 3, in the developing human epidermis reveals alterations in fetuses with inherited cutaneous disorders that may be important for prenatal diagnosis of these disorders.

Introduction Galectins constitute a phylogenetically conserved family of proteins that specifically bind to glycoconjugates bearing β-galactoside residues. Although galectin-1 (Gal 1), the first identified member of the galectin family, is involved in highly important biological processes at the molecular and cellular level in human skin, its expression in keratinocytes of normal human adult interfollicular epidermis (NHAIE) remains in dispute, whereas that in epidermal melanocytes has drawn very little attention so far. This prompted us to investigate the expression of Gal 1 in the keratinocytes and melanocytes of NHAIE. Methods Biopsy specimens obtained from the buttock skin of 23 healthy adult volunteers of both sexes were processed for single and double immunohistochemical staining using antibodies against Gal 1 and Melan-A. Results In contrast to epidermal melanocytes, which revealed a distinct Gal 1 immunoreactivity, keratinocytes of NHAIE were completely devoid of any expression of this galectin. Conclusions This article simultaneously assesses Gal 1 immunoreactivity of keratinocytes and melanocytes in NHAIE for the first time. Our findings may contribute to a better understanding of alterations in Gal 1 expression in various benign and malignant cutaneous disorders and may be of importance for the future design of targeted therapies.

An immunocompetent patient with extensive and recalcitrant common warts that was orally treated with isotretinoin (1 mg/kg/day) is reported. His lesions revealed a complete remission after 6 weeks of treatment, which was well tolerated. The patient has presently completed a 23-month follow-up and shows no evidence of relapse of his skin lesions. In view of these remarkable therapeutic results, further randomized controlled clinical studies in large numbers of patients are now warranted, which will definitely determine whether monotherapy with oral isotretinoin at a dose of 1 mg/kg/day may be regarded as a highly effective and well-tolerated therapeutic modality for extensive and recalcitrant common warts in both immunocompetent and immunocompromised patients.

The popularity of tattoos has increased dramatically worldwide particularly in the last three decades, giving rise to the frequent occurrence of a wide spectrum of secondary cutaneous and systemic complications. Pseudoepitheliomatous hyperplasia (PEH) is a benign irregular hyperplasia of the epidermis occurring in response to various stimuli, that clinically and histopathologically resembles cutaneous neoplasms such as squamous cell carcinoma and keratoacanthoma. In an attempt to improve the awareness of the possible occurrence of PEH in tattoos and of its diagnostic and therapeutic aspects, we present herein the case of a 30-year-old woman with histologically confirmed PEH related to a red-ink tattoo. She revealed two important features: the longest interval reported so far between tattooing and onset of PEH (two years) and the lack of the otherwise very common lichenoid tissue reaction to red ink. In view of the serious toxicological potential of tattoo inks, implementation of updated and standardized regulations worldwide regarding their use in the tattooing process is now urgently warranted and continuous efforts should be undertaken in order to enhance the awareness among tattoo artists and the public with regard to the possible serious health risks associated with the use of tattoo ink pigments.

Grover disease (GD) is a disorder of unknown origin, clinically characterized by the occurrence of pruritic, erythematous or brownish papules and papulovesicles, which histologically reveal four different patterns of acantholysis. Usually, the eruption is self-limited and spontaneously remit within a few weeks. In some cases, however, it may persist for months or even years and show a therapy-resistant course. We report a 56-year-old woman with recalcitrant, persistent, and generalized GD who showed complete remission after 6 weeks of treatment with oral acitretin (0.8mg/kg/day). The treatment was well-tolerated and laboratory parameters remained unchanged. The patient remains free of any recurrence at 26 months. To the best of our knowledge, this is the first report of a complete remission of the persistent form of GD as a result of oral acitretin monotherapy.

Galectins are a family of soluble proteins that are widely distributed in nature and bind to a variety of glycoproteins and glycolipids bearing β-galactoside residues. They are involved in highly important processes at the molecular and cellular level in human cutaneous and extracutaneous tissues, and they exert biological effects of paramount importance through their interaction with cytoplasmic and nuclear proteins and the components of the cell surface and extracellular matrix. Galectin 1 (Gal 1), the first galectin isolated, is a noncovalent homodimeric protein with a 14 kDa monomer that contains one carbohydrate-recognition domain (CRD) and preferentially recognizes galactose-β1-4-N-acetyl-glucosamine sequences on N- or O-linked glycans. Gal 1 occurs intracellularly, extracellularly, and on the cell surface. In the last few years Gal 1 has emerged as a multifaceted protein that exerts a wide spectrum of regulatory effects in diverse normal and abnormal tissues and conditions, indicating a tremendous therapeutic potential. This review summarizes current knowledge on the expression of Gal 1 in normal and diseased human skin, its implications in the pathogenesis, diagnosis, and prognosis of cutaneous disorders, and the novel approach to the treatment of these disorders offered by the use of Gal 1 or its inhibitors/antagonists.

Pemphigus vulgaris (PV) is an autoimmune disease of the skin and mucous membranes characterized by suprabasal acantholysis and formation of blisters and erosions due to generation of IgG autoantibodies directed against desmosomal proteins. Tissue expanders are devices that, through controlled mechanical overstretch, are capable of generating new skin that is used to cover wounds or extended surgical defects. We report the case of a 13-year-old girl suffering from Crohn's disease (CD) and primary sclerosing cholangitis (PSC) who developed PV after application of a tissue expander for surgical removal of a giant congenital melanocytic nevus (GCMN). To the best of our knowledge, the case presented here is the first report of PV possibly associated with the application of a tissue expander and also the first report of coexistence of PV with either PSC or with PSC and CD in the same patient. Triggering or acute exacerbation of PV may be considered a possible side-effect of tissue expander application, especially in patients with a genetic predisposition for pemphigus and/or other autoimmune diseases. In view of the increasing use of tissue expanders in clinical practice, physicians should be aware of this rare side-effect in order to promptly diagnose it.

Erythema multiforme is an immune-mediated cutaneous disorder that is thought to represent a hypersensitivity reaction to infections, drugs, vaccines, malignancies, autoimmune diseases, radiation, and menstruation. Golimumab is a human IgG1-kappa anti-TNF antibody that has been approved for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis. We report herein a 41-year-old woman with persistent erythema multiforme, that occurred 18 months after onset of golimumab treatment of her ulcerative colitis; the latter remains in full remission over a period of 36 months.

The efficacy of oral acitretin in the systemic treatment of severe and recalcitrant dermatoses has been established in a large number of clinical trials. Its mucocutaneous and ocular adverse reactions are common or relatively common, whereas systemic side effects are either uncommon or rare and include teratogenesis, hyperlipidemia, hepatotoxicity, intracranial hypertension, myopathy, and peripheral neuropathy. Angioedema is a term used to describe an acute, solitary or multiple, circumscribed, and non-pitting mucocutaneous swelling that affects the dermis and the subcutaneous tissue, lasts 24 to 72 hours, and may become potentially life-threatening when the pharynx and/or the larynx are involved. We report here the case of a 51-year old female psoriatic patient with angioedema (without urticaria) due to oral acitretin, confirmed by a positive oral provocation test. To the best of our knowledge, this is the second description of such an adverse reaction to acitretin.

Dear Editor, Molluscum contagiosum (MC) is a very common skin infection caused by a molluscipox virus gene of the poxvirus family. It usually occurs in young children, sexually active adults, and immunocompromised individuals. The typical clinical picture of this infection is characterized by asymptomatic flesh-colored, single or multiple papules, measuring 2-6 mm in diameter with a central umbilication that occur on the skin and the mucous membranes. In adults, the skin lesions are predominantly located in the genital region, whereas in children they are found on the trunk, the extremities, and the face. MC is generally regarded as a self-limited disease; however, its treatment is usually advisable considering its potentially protracted course and the risk of superinfection, scarring, autoinoculation, and transmission to other members of the community. A large number of approaches to the treatment of MC have been used so far (none of them approved by the Food and Drug Administration (FDA)) including ablative regimens (curettage, electrodessication, cryotherapy, laser therapy) and topical or systemic pharmacologic agents (tretinoin, cantharidin, trichloroacetic and salicylic acid, potassium hydroxide, interferon-alfa, and cimetidine). Imiquimod is a topically applicable Toll-like receptor (TLR)-7/8 agonist, which is capable of stimulating the innate cutaneous immunity and the cellular arm of the adaptive immune response and of exerting potent anti-viral, anti-tumor and immunoregulatory effects (1). Originally approved for the treatment of external genital and perianal warts in adults, imiquimod was later approved for the therapy of basal cell carcinomas and actinic keratoses and has also been used in the management of several off-label indications including cutaneous infections and neoplasms. Our group has successfully used topical imiquimod in the treatment of a variety of dermatoses including granuloma annulare, pyogenic granuloma, herpes labialis, and lichen striatus (2-6). Moreover, we have examined the topical application of imiquimod over the last twelve years in the treatment of 23 children with MC, the demographic data and the therapeutic response of which are summarized in Table 1. Seventeen out of 23 children (73.91%) treated with topical imiquimod once daily under occlusion (including two cases with disseminated lesions) showed a complete remission within 3 to 8 weeks of treatment. Furthermore, 6 other children who switched to other forms of treatment showed a partial remission (55.55%-84.61%) after 10 to 12 weeks of therapy. The only cutaneous adverse reaction to topical imiquimod was a mild to moderate irritation in the application area that was observed in all treated children, whereas no systemic side effects could be seen. Our findings are compatible with those of other groups, who also demonstrated the therapeutic efficacy and safety of topical imiquimod in MC. Interestingly, in two very similar subsequent papers Katz and Swetman (7) and Katz (8,9) expressed the view that "imiquimod is neither efficacious nor safe in the treatment of MC in children". This view was not the result of the author's clinical experience but was exclusively based on the findings of two randomized clinical trials (RCTs). These were carried out in 2006 upon request of the FDA from the drug's original manufacturer (3M) and "definitely showed that imiquimod does not effectively treat MC in children". Surprisingly, today, 10 years after their completion, these RCTs still remain unpublished, whereas the corresponding FDA site provides no information with regard to the researchers, the centers in which these trials were conducted, their research protocol, and the demographic data of the enrolled patients. In a very recent review on childhood skin infections, Rush and Dinulos (10), exclusively based on Dr. Katz's paper, fully adopted this view and stated that "imiquimod is neither efficacious nor safe in the treatment of MC", although they admit that the RCTs cited by the latter still remain unpublished. In contrast to these authors, we reject Dr Katz's inexplicable request to the medical community to fully ignore all articles published in peer-reviewed journals that demonstrate the efficacy and safety of imiquimod in MC. We do not claim that imiquimod is a panacea. However, based on our clinical experience and that of other groups, we are convinced that this compound represents a very useful and painless tool in the dermatologic arsenal for the treatment of MC, an otherwise difficult to manage dermatosis, particularly in children.

Eosinophilic pustular folliculitis (EPF) is a rare noninfectious pruritic dermatosis, first described by Ise and Ofuji in 1965. We report the case of a 15-year oldimmunocompetent girl that presented with a widespread papulopustular eruption four days after her arrival in Japan. The clinical diagnosis of the classicform of EPF was confirmed by histological examination of the lesional skin that revealed an intense, mainly eosinophilic, dermal infiltrate within and aroundpilosebaceous units. Oral administration of lowdose indomethacin (25 mg/day) led to a complete resolution of the eruption within 6 weeks without causing any side effects. The patient is presently completing a 15-month follow-up and remains free ofrelapses. To the best of our knowledge, it is the first time that low-dose oral indomethacin is reported to be capable of causing a rapid and complete resolutionof the classic form of EPF.

Erythema multiforme (EM) is an acute and usually self-limited immune-mediated mucocutaneous disorder that is a hypersensitivity reaction to drugs, infections, and vaccines. Clinically, it is characterized by maculopapular, target-like lesions symmetrically distributed on the extremities (minor form) or additionally affecting one or more mucous membranes and causing epidermal detachment involving < 10% of the total body surface area (major form). We report a novel association between pneumococcal vaccination and the development of EM in a 2.5-year-old boy. The introduction of 13-valent-polysaccharide-pneumococcal-conjugate vaccine (PCV13) into vaccination programs has resulted in a reduced incidence of pneumococcal disorders. Systemic side effects of PCV13 include chills, fever, headache, vomiting, fatigue, arthralgia, myalgias, decreased appetite, and diarrhea, whereas its cutaneous adverse reactions are local injection site reactions, Sweet's syndrome, and deep morphea. EM is triggered by a variety of vaccines; however, as far as we know, it has not previously been reported in association with pneumococcal vaccine. Although a fortuitous occurrence of EM in our patient cannot be absolutely excluded, it appears very likely that PCV13 caused the patient's eruption, considering the history and the laboratory data, which point toward a lack of any other causative factors.

We report a 40-year-old male patient with widespread chronic plaque psoriasis, who complained of distal numbness in the right leg with gradual proximal extension after 1 month of treatment with oral acitretin. Neurological examination showed suppressed ankle reflexes, reduced pain and vibration sense in a glove and stocking distribution, and mild weakness of feet dorsiflexion. Neurophysiologic examination revealed a shift of the amplitude of all sensory and compound muscle action potentials toward low values, whereas in the case of sural and popliteal nerves, the amplitude felt below reference limits. Follow-up examination of the patient 1 month after treatment discontinuation revealed no abnormal neurological symptoms or signs, whereas the values of the neurophysiologic measurements had returned to normal levels. The case of sensorimotor polyneuropathy presented herein underlines the necessity for detailed neurological and neurophysiologic examinations of patients before and during oral administration of acitretin.

A 40-year-old HIV-negative Greek woman was admitted to the Department of Neurology at the University Medical Center of Patras with a 4-day history of progressive muscle weakness in her legs, accompanied by fever (39.5°C), diarrhea and urine retention and a 6-year history of oral and genital lesions that had relapsed 20 days prior to admission. Physical examination revealed multiple large aphthous lesions in the oral mucosa, extensive and deep anogenital ulcers, pseudofolliculitis and pathergy signs but no evidence of arthritis. Initial neurological examination showed muscle power grade 3/5 [Medical Research Council (MRC) scale] in the proximal and grade 4/5 in the distal muscles], brisk symmetrical tendon reflexes, extensor plantar response bilaterally, severe suppression of vibration sense below the knees (particularly on the right extremity) and bilateral reduction of pain appreciation below the T5 level. Neurological disability score in the expanded disability status scale (EDSS) was 6.5, indicating that bilateral assistance was required to walk 20 m. Cranial nerves and motor and sensory function of upper limbs were normal. Magnetic resonance imaging (MRI) of thoracic spinal cord revealed a long intramedullar lesion extending from C7 to T7 vertebrae with gadolinium-enhancement at T3–T4 level, whereas that of the brain showed three unenhanced small lesions at the brainstem (Figure 1.). Cerebrospinal fluid analysis revealed 60 lymphocytes/ml, normal protein and glucose content and negative oligoclonal bands. Figure 1. Magnetic resonance scan of the thoracic cord (sagittal T1-weighted images with gadolinium) showing the intramedullary enhanced lesion before (left image) and 1 month after treatment (right image). Ophthalmologic investigation disclosed posterior uveitis and spotty hemorrhagic foci on both eyes, whereas colonoscopy showed multiple deep ulcers along the large bowel. Erythrocyte sedimentation rate was 70 mm/h, HLA B51 was positive, whereas serum protein electrophoresis revealed a decrease …

Ribonuclease P (RNase P) is ubiquitous and essential Mg(2+)-dependent endoribonuclease that catalyzes the 5'-maturation of transfer RNAs. RNase P and the ribosome are so far the only ribozymes known to be conserved in all kingdoms of life. Eukaryotic RNase P activity has been detected in nuclei, mitochondria and chloroplasts and demonstrates great variability in sequence and subunit composition. In the last few years we have developed methodologies and pursued projects addressing the occurrence, distribution and the potential physiological role of RNase P in human epidermal keratinocytes. In view of the vital importance of lymphocytes for an effective immune system and their successful application after transfection with RNase P-associated external guide sequences in gene therapy, we concerned ourselves with the isolation and characterization of RNase P of peripheral human lymphocytes. We developed a method described herein, that will enable the study of the possible involvement of this ribozyme in the pathogenetic mechanisms of diverse autoimmune, inflammatory and neoplastic cutaneous disorders and may facilitate the further development of RNase P-based technology for gene therapy of infectious and neoplastic dermatoses.

Background: Dyskeratotic cells in Darier’s disease (DD) are thought to represent apoptotic keratinocytes. Bcl-2 gene family proteins play a major role in the regulation of apoptosis of epidermal keratinocytes and reveal pleiotropic interactions with intracellular Ca2+ homeostasis. The latter is impaired in DD because of mutations of ATP2A2 gene that encodes the type 2 isoforms of the sarcoplasmic/endoplasmic reticulum (ER) Ca++ ATPase 2 (SERCA2) pump. Methods: The expression of Bcl-2, Bax, and Bcl-xL proteins was investigated in the epidermis of 11 patients with DD and of 11 sex- and age-matched healthy controls by immunohistochemistry. Results: The expression of Bcl-2 and Bcl-xL was clearly reduced in the lesional epidermis of the patients, as compared with the normal epidermis of healthy controls, whereas the expression of Bax remained unaltered. Conclusions: The alterations in the expression of Bcl-2 gene family proteins could be a crucial event for the activation of the apoptotic process in the lesional epidermis of DD patients and for the occurrence of the characteristic dyskeratotic keratinocytes. The question as to whether these alterations are associated with the ER Ca2+ depletion in DD or represent secondary phenomena unrelated to the genetic defect of this genodermatosis remains to be elucidated.

Heat shock protein 27 (Hsp27), apart from its protective function in response to stress, is implicated in the regulation of cell growth, differentiation and apoptosis. Data on the expression of Hsp27 in the developing human epidermis are sparse and partially conflicting. Thus, the purpose of the present study was to investigate Hsp27 expression during the morphogenesis of human epidermis. Skin biopsies and dispase-separated epidermal sheets obtained from 7 human embryos (7 and 8 weeks estimated gestational age, EGA), from 79 human fetuses (9-23 weeks EGA) and from 10 healthy adult volunteers were investigated by immunohistochemistry and Western blotting, respectively. The earliest detection of Hsp27 expression was found by immunohistochemistry at the 12th week EGA (basal and intermediate layer) and by Western blotting at the 9th week EGA. From the 16th to the 23rd week EGA immunoreactivity was not detectable in the basal layer, whereas in the overlying layers it revealed a differentiation-related pattern. The simultaneous onset of epidermal stratification and Hsp27 expression (9th week EGA) and the alterations of the latter in the subsequent stages of development, suggest that this stress protein may be involved in the molecular events underlying human epidermal morphogenesis.

We present here the course of clinical response of a 53-year-old haemodialysed Fabry patient who received recombinant human a-galactosidase A at a dose of 1 mg/kg every other week over a period of 1 year. The therapy was well tolerated by the patient, who revealed an impressive favourable cutaneous, gastrointestinal, neurological and psychiatric response and a dramatic improvement in his quality of life, but no improvement in cardiac and renal function. Key words: a-galactosidase A; angiokeratoma; dialysis; diarrhoea; depression; globotriaosylceramides; oedema.

The purpose of this prospective study was to investigate the ocular side effects of short-term therapy with oral acitretin (1 mg/kg/day) in 24 patients with severe and recalcitrant dermatoses. Apart from the routine ophthalmological examination, the following tests were performed: break-up time of tear film for the determination of its stability, Schirmer test for the assessment of lacrimal gland function, rose bengal staining for the detection of possible ocular surface damage and contrast sensitivity test for the evaluation of visual function. No statistically significant differences could be found between the pretreatment values of the assessed parameters and those obtained after 1 and 2 months of therapy. It seems reasonable, therefore, to suggest that ocular surface integrity and tear film and visual function are not affected by short-term oral acitretin administration.

The purpose of this double-blind randomised parallel-group study was to compare the efficacy and safety of short-contact treatment with dithranol ointment (2%) with its combination with calcipotriol ointment (50 µg/g) in 2 groups of in-patients with chronic plaque psoriasis. The patients of the first group (n = 23) topically applied dithranol once daily for 30 min and the vehicle of calcipotriol twice daily. The patients of the second group (n = 23) used a single topical application of dithranol for 30 min daily and additionally applied calcipotriol twice daily. The extent and the severity of psoriasis were assessed by means of psoriasis area and severity index score (PASI score) before the onset of the 6-week therapy and weekly thereafter. The difference between the two groups with regard to the mean PASI score became statistically significant already after the first week of treatment and remained so until the end of the trial. No significant differences were observed between the two groups with respect to the cutaneous adverse events. These findings indicate that the addition of calcipotriol ointment to short-contact dithranol markedly augments the therapeutic efficacy of the latter in chronic plaque psoriasis and impressively accelerates the response of psoriatic plaques to this well-tolerated regimen.

The effects of two antipsoriatic compounds, calcipotriol and anthralin, separately or in combination on ribonuclease P (RNase P), were investigated using a cell-free system from the slime mold Dictyostelium discoideum . RNase P is an ubiquitous and essential enzyme which endonucleolytically cleaves all tRNA precursors to produce the mature 5′ end. The substrate for RNase P assays was an in vitro 32 P-labeled transcript of the Schizosaccharomyces pombe tRNA Ser gene supS1. Enzyme assays were carried out at 37° in 20 μL 50 mM Tris–HCL 7.6 buffer, containing 10 mM NH 4 Cl, 5 mM MgCl 2 , and 10% isopropanol. Calcipotriol or anthralin alone exerted a dose-dependent inhibitory effect on RNase P activity, with the former being more active than the latter in this respect. Simultaneous exposure of the enzyme to both drugs resulted in an enhancement of RNase P inhibition, which was additive. Considering the lack of structural similarities between the substrate (precursor tRNA) of RNase P and the tested drugs, it seems reasonable to suggest that their effects may be due to binding to allosteric inhibition sites of the enzyme. Although our in vitro findings cannot be directly extrapolated to the in vivo human condition, they do suggest that the inhibitory effects of calcipotriol and anthralin on tRNA biogenesis may be implicated in the mechanisms of their antipsoriatic action. Moreover, the additive inhibitory effect of these compounds on RNase P activity provides an experimental basis for their possible combined therapeutic application in the management of psoriasis.

Using a new computerized methodological procedure a separate analysis and a quantitative determination of the viscous and elastic parameters of the scalp hair shaft were performed in 37 neonates of both sexes with a gestational age of 28-29 weeks (n = 16) and 39-40 weeks (n = 21), respectively. A statistically significant (p < 0.001) decrease in the values of modulus of elasticity (Eα) was found in the hair shaft of premature neonates, as compared to the full-term ones, whereas the values of postyield slope (Eβ) and of SDIS/SSTOR (viscous parameter) did not significantly differ in the two groups. The decrease in modulus of elasticity in the hair shaft of premature neonates may be interpreted in terms of an insufficient number of disulphide bonds between the α-helical keratin units of the hair cortex or of a disordered arrangement of microfibrils within the matrix. Further studies are now warranted to determine the pattern of mechanical parameters of the scalp hair shaft in large numbers of newborn infants of different gestational ages and to answer the question as to whether this pattern might be useful in the accurate postnatal assessment of fetal maturation.

We report a 72-year-old male patient with a 47,XYY/45,X/46,XY mosaicism associated with short stature, exostoses, type E brachydactyly, gynecomastia, cryptorchidism, mild mental retardation, and a paranoid personality and conversion disorder. Since his prevalent cell line was 47,XYY (about 75%), our patient could be karyotypically classified as a case of 47,XYY syndrome. In view of the striking similarity of the clinical features of this case and those of a XYY case previously reported by Ikegawa et al (1992), it seems reasonable to suggest that these patients are representatives of a novel syndrome with a XYY karyotype.

The case of a 35-year-old man is reported who developed a spontaneous anaphylactic shock as the only clinical manifestation of hepatic hydatidosis. Dermatologists should consider asymptomatic hydatid disease in the differential diagnosis of anaphylactic reactions, particularly in patients from regions in which echinococcosis is endemic.

A 69-year-old Caucasian HIV-negative woman presented to the Department of Dermatology at the Patras University Medical Center with a 3-year history of progressively enlarging disfiguring masses over the upper part of her body. She had no history or evidence of systemic infections, autoimmune or neoplastic disorders. Additionally, she had no history of alcohol abuse and her family history was unremarkable. The patient presented with a height of 158 cm, a weight of 108 kg and a body mass index of 43.3. Physical examination revealed extremely large, painless and symmetrical subcutaneous masses on the neck, shoulders, proximal arms and axillae (Figure 1). She experienced no discomfort, dyspnea, dysphagia or dysphonia. Histological examination of the nonencapsulated masses showed a network of mature adipocytes without evidence of increased vascularity or malignancy. Based on these findings, the diagnosis of multiple symmetric lipomatosis (MSL) (type I) was established. Figure 1 Anterior ( A ) and lateral view of the patient ( B ). On clinical neurologic examination, there was a weakness of the proximal leg muscles (4/5 Medical Research Council score), whereas motion of the shoulder muscles was limited probably due to the fat deposits. Apart from ankle reflexes, all tendon reflexes were present and symmetrical. Pain and touch sense were moderately reduced in a stocking distribution up to the knee level bilaterally and normal in the upper limbs. Vibration sense and …

We describe a patient with severe nodulocystic acne who developed disabling muscle stiffness and painful superimposed spasms of the neck, back and upper limbs 10 days after the onset of oral isotretinoin treatment. The muscle hyperactivity condition, which revealed the clinical and electromyographic features of the stiff-person syndrome, gradually resolved 2 weeks after drug withdrawal.

Background Given the limitations of current antiviral therapies, safer and more effective approaches to the management of recurrent herpes labialis (RHL) are needed. Methods A patient with a 23-year history of RHL and 14 healthy individuals were studied. The patient applied imiquimod to distant healthy skin for 3 weeks. Peripheral blood (PB) samples were collected from the patient during treatment and 21 months after its discontinuation; samples were collected from the controls once. The distribution of lymphocyte populations in PB were analysed by flow cytometry and PB cytokine levels were measured using cytometric bead arrays. Results The patient showed long-term remission of the disorder subsequent to a 3-week imiquimod application to distant healthy skin. Imiquimod treatment induced the activation and proliferation of T-helper and cytotoxic T-cells, B-cells and T-regulatory cells. In addition, there was a very strong transient increase of T-helper 1 cells (resulting in interferon-γ secretion) and type 1 (pro- inflammatory) polarization of the immune response accompanied by a sustainable interferon-α production. At follow-up 21 months after treatment cessation, with the patient remaining relapse-free, the patient had control levels of all cytokines, increased levels of activated cytotoxic T-cells, continuous production of new T-helper cells and B-cells and near-to-normal levels of T-regulatory cells. Conclusions Our results indicate that topical application of imiquimod to healthy skin is capable of causing systemic immunomodulation. This treatment might represent a new and effective alternative to established therapeutic and prophylactic regimens for RHL.

The aim of this study was to determine whether imiquimod, a Toll-like receptor-7/8 agonist, in addition to its well-known topical action on the cutaneous immune response, might also induce alterations in the peripheral blood lymphocytes. A 62.5 mg quantity of imiquimod (5% cream) was applied topically under occlusion once daily every second day for 3 weeks to the skin of 10 healthy volunteers, age range 30–57 years. Ten sex- and age-matched healthy controls applied corresponding quantities of the vehicle under occlusion. Before, and one and 3 weeks after the start of treatment, peripheral blood lymphocyte subpopulations were measured by flow cytometry. Statistically significant alterations in the percentage or absolute numbers of peripheral blood lymphocyte subpopulations were found in the imiquimod-treated group compared with the control group. These alterations indicate for the first time that topical application of imiquimod induces alterations in peripheral blood lympho cyte subsets in healthy individuals, which may be of importance in the immunotherapy of neoplastic and infectious disorders and should be taken into careful consideration in patients who are treated with imiquimod.

An 82-year-old man was referred to our department for evaluation and treatment of a recurrent pyogenic granuloma on his right hand. After previous histopathological confirmation of the clinical diagnosis, he had been treated twice with electrocautery, but the lesion recurred 10 and 8 days later, respectively. After a 3-week topical application of imiquimod 5% cream twice daily under occlusion, complete remission of the lesion was achieved. Apart from an erythematous reaction in the apparently normal surrounding skin, the patient experienced no local or systemic side-effects. Since discontinuation of treatment he has been followed up for 8 months, and there has been no recurrence.

Accumulating evidence suggests the involvement of neurogenic inflammation in the pathogenesis of psoriasis. Moreover, the concomitant occurrence of peripheral neuropathy has been reported in several psoriatic patients. Thus, the aim of the present study was to answer the question whether an impairment of peripheral large nerve fibre function may exist in psoriasis. Thirty-two patients with severe and generalized chronic plaque psoriasis and 32 sex- and age-matched healthy controls were evaluated by detailed clinical neurological and standard neurophysiological examination. The latter included motor nerve conduction study of one nerve in the upper and one in the lower extremities and sensory nerve conduction study of one nerve in the upper and two in the lower extremities. Neurological examination failed to demonstrate any clinical evidence of large fibre neuropathy. Furthermore, all values of the examined neurophysiological parameters were within normal limits; comparisons of the corresponding mean values in the patient and the control group showed no statistically significant differences. These findings demonstrate no measurable abnormalities of the peripheral large nerve fibres in psoriatic patients and therefore an association of psoriasis with peripheral large fibre neuropathy cannot be suggested.

Ribonuclease P (RNase P) is a key enzyme in tRNA biogenesis that catalyses the endonucleolytic cleavage of tRNA precursors and generates their mature 5' ends. The activity of this ribozyme has never been isolated from living human tissues and data about epidermal tRNA biogenesis are not available. The purpose of the present study was to isolate and purify RNase P from human epidermis and to investigate the in vitro effects of retinoids on its activity. Enzyme isolation and purification from homogenates of keratinocytes derived after trypsinization from dispase-separated human epidermis were carried out using phosphocellulose chromatography. The optimal activity of the enzyme was found at 100 mM NH4Cl and 5 mM MgCl2 at pH 7.5 and 37 degrees C. All-trans retinoic acid and acitretin revealed a dose-dependent inhibitory effect on RNase P activity. The isolation of RNase P activity from human epidermis, reported here for the first time, will enable the investigation of the possible involvement of this ribozyme in the regulation of epidermal differentiation and proliferation and the evaluation of its significance for the pathogenesis and gene therapy of various cutaneous disorders.

Subclinical neurophysiologic abnormalities mainly suggestive of sensory fibers dysfunction were observed in some patients after 1 and 3 months of treatment with oral acitretin. Moreover, two cases of peripheral sensory neuropathy and one of sensorimotor polyneuropathy were observed after short-term oral administration of this compound.The objective of this prospective study was to investigate whether short-term treatment with oral isotretinoin can also affect peripheral nerve function.Serial neurologic and neurophysiologic examinations were performed on 18 young patients with severe nodulocystic acne prior to and 1 and 3 months after the onset of oral isotretinoin treatment (1 mg/kg per day).Clinical neurologic examination before and under treatment disclosed no abnormalities in any of the patients. There were no significant differences between the pre- and post-treatment neurophysiologic parameters. Furthermore, evaluation of the serial neurophysiologic measurements in each patient separately under oral isotretinoin treatment revealed no changes fulfilling the criteria of abnormality.Short-term administration of oral isotretinoin in young patients does not cause clinical or subclinical neuropathy.

Down syndrome, a common chromosome aneuploidy, has been associated with an increased incidence of cutaneous disorders. The simultaneous occurrence with Ehlers-Danlos syndrome (EDS) is rare. We report here the clinical case of a 19-year-old female patient with Down syndrome (trisomy 21) who was also affected by EDS type IV. She died from spontaneous bleeding due to rupture of nonaneurysmal abdominal aorta. Since the affected chromosomes in these two syndromes are different (21 and 2, respectively), the concomitant appearance of Down syndrome and EDS type IV in our patient, though clinically intriguing, most likely represents a co-occurrence. However, the possibility that a presently unknown link may exist between these syndromes cannot be ruled out.

The purpose of this study was to investigate the carbohydrate residue composition of cell surface in the developing epidermis and to define the chronological sequence of its alterations in human fetuses from the 10th to the 20th weeks of gestation and at the 23rd week of gestation, using a panel of six biotinylated lectins: Concanavalin A, Ulex europaeus agglutinin-I, Ricinus communis agglutinin-I, Peanut agglutinin, Wheat germ agglutinin, and Dolichos biflorus agglutinin. Distinct qualitative and quantitative alterations in the expression of cell surface carbohydrate residues were found during epidermal morphogenesis prior to keratinization (10th to 20th weeks). At the 23rd week of gestation, the already keratinized fetal human epidermis revealed a pattern of cell surface glycosylation very similar to that of the adult human epidermis. Further studies are now warranted to answer the question regarding whether the glycosylation pattern in the developing human epidermis is disturbed in fetuses with genodermatoses and whether these disturbances might be important for prenatally diagnosing the latter.

Background: The results of the very few histochemical studies that have been performed so far on the lectin-binding profile of normal human epidermis are mostly controversial; thus, the carbohydrate residue composition of the cell surface in the latter still remains in dispute and the possible alterations in the epidermal lectin-binding profile are unknown. Objective: To investigate the influence of age on the carbohydrate residue composition of the cell surface in unexposed normal human epidermis by means of lectin histochemistry. Methods: Biopsy specimens obtained from the sun-protected (unexposed) buttock skin, divided into 5 age groups of 18 subjects each, were fixed in buffered formalin (10%) and embedded in paraffin. 4-µm sections were processed for histochemistry using a panel of six biotinylated lectins. Results: In the unexposed normal human epidermis the concentration and distribution of cell surface β-D-galactose, D-galactose-β-(1,3 N-acetylo-D-galactosamine), β(1,4 D-N-acetylo-D-glucosamine) and α-D-N-acetylo-D-galactosamine were almost identical in all age groups, whereas those of α-D-mannose, α-D-glucose and α-L-fucose revealed significant age-related differences. Conclusion: These findings may be due to an age-related decline in synthesis and/or transport of monosaccharides from the cytoplasm to the surface of epidermal cells. Thus, the corresponding lectins concanavalin A and Ulex europaeus agglutinin-I can only be used in comparative histochemical studies of the carbohydrate residue composition of the cell surface in the normal and pathological epidermis of individuals of the same age, whereas Ricinus communis agglutinin-I, peanut agglutinin, wheat germ agglutinin and Dolichos biflorus agglutinin, whose binding to carbohydrates is not affected by aging can be used in histochemical studies of carbohydrate residue composition of the cell surface in the normal and pathological epidermis in human subjects of any age.

Objective The objective of this study is to identify early patients who are at-risk for major depression (MD) induced by interferon-α (IFN-α) and evaluate the response of depressive symptoms to antidepressants. Methods Thirty-six consecutive patients were treated with IFN-α. Psychiatric evaluations were performed prior to, and at 1 and 2 months after onset of therapy and upon completion of the study. Diagnoses were made according to DSM-IV criteria, and the severity of depressive symptoms was determined by the Hamilton Depression Rating Scale score (HDRSS). Results Of the 36 patients studied, 7 (19%) had MD before IFN-α treatment, 6 of which manifested a worsening of the depressive symptomatology during treatment. Of the remaining 29 patients, 9 (31%) developed MD during treatment. The median time required for the appearance or worsening of the depressive symptoms was 15 days (range 7–25). The median HDRSS before IFN-α in the 36 patients was 3 (range 1–20), whereas after 1 month of therapy, it was 10 (range 1–24; P =.000004). There was a strong positive correlation in the HDRSS before and 1 month after the initiation of treatment ( r =.863). Of the 14 patients with a HDRSS of 1–2 before IFN-α treatment, only 1 (7%) developed MD, whereas of the 15 patients with a score >3, 8 (53%) developed MD. Antidepressants resulted in a decrease of the HDRSS to the IFN-α pretreatment values. Conclusion One third of those treated with IFN-α developed MD. The HDRSS before treatment reveals the high- and low-risk patients for developing MD. Psychiatric evaluation should be performed prior to IFN-α treatment.

We report a patient with chronic plaque psoriasis who developed clinical and electrophysiologic features of polyneuropathy affecting motor and sensory fibers in upper and lower extremities after three months of treatment with oral acitretin. Drug withdrawal resulted in a complete clinical recovery and normalization of all electrophysiologic abnormalities within two months.

The aim of the present prospective study was to substantiate possible side effects of short-term oral acitretin therapy (1 mg/kg/day) on peripheral nerve function of 13 patients with severe keratinization disorders. Clinical neurological examination before and 1 and 3 months after onset of treatment was unremarkable in all patients; however, a significant alteration of one or more neurophysiological, predominantly sensory, parameters was demonstrated in 3 out of 13 patients (23%) after 1 month and in 9 out of 13 (69%) after 3 months of oral acitretin therapy. These findings indicate that oral acitretin might be capable of causing a dysfunction of predominantly sensory nerve fibres in some individuals. Although in the investigated patients this dysfunction remained subclinical, it seems reasonable to suggest that neurological and neurophysiological evaluation of peripheral nerves should be added to the list of investigations that are routinely performed in patients receiving oral acitretin.

A 57-year-old female patient with widespread chronic plaque psoriasis and a 32-year-old male patient with severe oral lichen planus are reported, who developed sensory symptoms in the extremities 3 and 4 months after the onset of oral acitretin therapy, respectively. Both patients showed clinical and electrophysiological evidence of a sensory peripheral neuropathy, which completely resolved 2 and 2.5 years after discontinuation of oral acitretin administration, respectively.

A panel of six biotinylated lectins was applied in order to study the composition and distribution of plasma membrane carbohydrate residues in 83 primary cutaneous melanomas (MMs) and in 85 melanocytic nevi (MN) with the avidin-biotin peroxidase technique. No clear-cut differences between MN and MMs were observed with regard to the staining with lectins. In MN and MMs derived from different patients, the lectin-binding pattern was variable and heterogeneous even within the individual nevi or melanomas. It seems reasonable, therefore, to assume that the lectin-binding pattern cannot be regarded as a reliable histochemical marker for the differentiation of MN from MMs. Moreover, because the pattern reveals no statistically significant correlation with the thickness or the depth of invasion of MM, it seems to lack prognostic significance.

Eight male patients with overt clinical and biochemical features of porphyria cutanea tarda (PCT) were orally treated with 300 mg/day thalidomide for 1 week and with 200 mg/day for 3 more weeks. Already after the first week of treatment no new vesicles and/or bullae could be observed. Spontaneous blisters completely disappeared, increased skin fragility subsided and skin hyperpigmentation receded about 2 months after completion of therapy, whereas hypertrichosis persisted. There was a rapid decrease in the urinary total porphyrin excretion which reached normal levels in all patients by the end of the fourth week of therapy, whereas the posttreament chromatographic pattern of urinary porphyrins revealed a slight reduction of higher carboxylated porphyrin metabolites and an increase in the amount of the excreted coproporphyrin, as compared to the pretreatment period. Somnolence, intermittent constipation and dry mouth occurred in all patients, 2 patients additionally experienced dizziness. No evidence of peripheral neuropathy could be detected and laboratory investigations revealed no abnormalities, as compared to the pretreatment period. During the 16- to 28-month follow-up of the patients, no clinical or biochemical relapse was observed. In view of the encouraging results of the present investigation, further studies are now warranted in order to definitely answer the question whether oral thalidomide may be regarded as an effective alternative approach to the treatment of PCT.

We report a 31-year-old female patient with cutaneous sarcoidosis, who showed a complete remission of her single system skin disease after an 8-month therapy with oral isotretinoin (1 mg/kg/day). At 15-month follow-up, the patient still remained free of recurrence and visceral involvement.

Georgiou S, Monastirli A, Pasmatzi E, Gartaganis S, Goerz G, Tsambaos D (Departments of Dermatology and Ophthalmology, University of Patras, Greece and the Department of Dermatology, Heinrich-Heine University of Dusseldorf, Germany). Efficacy and safety of systemic recombinant interferon-alpha in Behcet's disease. J Intern Med 1998; 243: 367–72. Objectives To evaluate the therapeutic efficacy and safety of systemic recombinant interferon α-2a (IFN -α) in patients with Behcet's disease (BD) and to determine the incidence of episodes in complete responders during the one-year pretreatment period and follow-up. Design An open clinical study. Setting Departments of Dermatology and Ophthalmology, University of Patras, Greece and Department of Dermatology, Heinrich-Heine University of Dusseldorf, Germany. Subjects Twelve patients (aged 23–52 years) with active BD who had previously been unsuccessfully treated with systemic steroids and/or immunosuppressives. Interventions IFN-α was administered subcutaneously at a dose of 6 × 106 IU per day 3 times per week for 2 months. Main outcome measures Change of area or number of mucocutaneous lesions, grading score for thrombophlebitis and ocular inflammation, haematological and biochemical parameters and number of episodes during the pretreatment period and the follow-up. Evaluation of IFN-α side effects. Results Nine patients (75.0%) revealed a complete remission, two (16.6%) a partial remission and one patient (8.3%) showed no response. During the follow-up in five out of the nine complete responders (55.5%) no episodes of BD were seen, whereas, the other four patients (44.5%) had 1–2 episodes, as compared to 5–8 and 5–12 episodes, respectively, during the pretreatment period. An influenza-like syndrome (fever, nausea and myalgias) appeared during the early phase of therapy in all (but one) patients. No patient had to discontinue IFN-α because of intolerance. Conclusions Subcutaneous human recombinant interferon α-2a appears to be an effective and fairly well tolerated therapy for BD.

The histological similarities of seborrhoeic keratoses and common warts led to the investigation of the possible occurrence of human papillomavirus DNA (HPV-DNA) in a large number of nongenital seborrhoeic keratoses using the in situ hybridization technique. All specimens derived from normal skin (n = 173) were negative for the applied HPV-DNA probe, whereas the HPV genome was detected in 34 of 173 seborrhoeic keratosis specimens (19.65%). Of 34 HPV-positive specimens, 15 contained types 6/11 and 14 types 31/33/35, and 5 showed no positive reaction to the applied types. These results suggest that a considerable percentage of nongenital seborrhoeic keratoses may be related to an HPV infection.

Sir, Imatinib mesylate (formerly STI 571, now referred to as Glivec in Europe andGleevec in theUnited States) is a rationally developed, orally administered potent competitive inhibitor of the BCR-ABLprotein tyrosine kinase that reveals a significant efficacy and a favourable safety profile in patients with chronic myeloid leukaemia (CML) (1). This compound has been reported to be effective also in gastrointestinal stromal tumours unresponsive to standard chemotherapy (2) and in metastatic dermatofibrosarcoma protuberans (3). We report here a patient who developed a skin rash during treatment with imatinib mesylate.