Alterations in the spatiotemporal expression pattern of geminin during human epidermal morphogenesis.

INTRODUCTION: Geminin, a (25 kDa) protein, was originally identified as a key regulator of DNA replication licensing in the cell cycle and of cell fate during embryonic nervous system formation. Although geminin is involved in mechanisms underlying the regulation of transcription and patterning in embryonic development, its expression and possible significance in human epidermal morphogenesis remains unknown. METHODS: Forty-one skin biopsy specimens obtained from human fetuses (10th to 23rd week of estimated gestational age) were processed for immunohistochemistry using a primary rabbit polyclonal antibody against geminin. RESULTS: Distinct and statistically significant qualitative and quantitative alterations in the spatiotemporal expression pattern of geminin were observed in the developing human epidermis. CONCLUSIONS: The highly ordered expression of geminin in different layers of fetal human epidermis reported here for the first time suggests that this protein may play a significant role in epidermal morphogenesis. However, the mechanisms underlying the alterations of the geminin expression pattern during fetal development at the molecular level remain to be elucidated. Further studies are now warranted to address whether the expression pattern of geminin in the developing human epidermis is disturbed in fetuses with genodermatoses and whether these disturbances might be important for prenatal diagnosis of genodermatoses.

Herpes Zoster after mRNA COVID-19 Vaccination: A Case Series.

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. (SKINmed. 2022;20:284-288).

Condylomata acuminata, Bowenoid papulosis, and squamous cell carcinoma, all positive for human papillomavirus type 16/18 DNA, coexisting in the genital area: a case report.

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.

The expression pattern of galectins during human epidermal morphogenesis.

INTRODUCTION: Galectins constitute a phylogenetically conserved family of proteins with high binding affinity for glycoconjugates bearing ß-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.

In contrast to melanocytes, keratinocytes of normal human adult interfollicular epidermis do not express galectin-1.

INTRODUCTION: Galectins constitute a phylogenetically conserved family of proteins that specifically bind to glycoconjugates bearing ß-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.

Erythema nodosum induced by oral isotretinoin in a patient with condylomata acuminata.

Erythema nodosum (EN) is a form of septal panniculitis, which is believed to represent a delayed hypersensitivity reaction activated by infectious agents, drugs, granulomatous and autoimmune diseases, pregnancy, and malignancies. There are only four reported cases of EN during oral isotretinoin therapy to our knowledge, all of them occurring in patients with severe acne. Since acne itself can trigger EN, the question as to whether there is indeed a causative relationship between isotretinoin and EN in the reported cases remains to be elucidated. We present herein a 20-year-old woman with multiple vulvar condylomata acuminata who developed EN two weeks after onset of oral isotretinoin therapy. To the best of our knowledge, this is the first report of EN occurring during isotretinoin treatment in a patient without acne and strongly indicates that the pathogenesis of EN can be directly related to the biological actions of isotretinoin. Erythema nodosum should be regarded as a rare side effect of oral isotretinoin therapy, regardless of the underlying disease. Physicians should be aware of this rare side effect.

Extensive and recalcitrant common warts in an immunocompetent patient: rapid and complete remission after oral isotretinoin monotherapy.

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.

Pemphigus vulgaris possibly associated with application of a tissue expander in a patient with Crohn's disease and primary sclerosing cholangitis.

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.

Galectin 3: an extraordinary multifunctional protein in dermatology. Current knowledge and perspectives.

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.

Late-onset pseudoepitheliomatous hyperplasia developing within a red ink tattoo.

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.

Galectin 3: an extraordinary multifunctional protein in dermatology. Current knowledge and perspectives

Abstract: 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.

Persistent generalized Grover disease: complete remission after treatment with oral acitretin.

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.

Galectin 1 in dermatology: current knowledge and perspectives.

Galectins are a family of soluble proteins that are widely distributed in nature and bind to a variety of glycoproteins and glycolipids bearing ß-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-ß1-4-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.

Golimumab-associated persistent erythema multiforme in a patient with ulcerative colitis in full remission.

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.

Angioedema without urticaria caused by oral acitretin.

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.

Topical Imiquimod is an Effective and Safe Drug for Molluscum Contagiosum in Children.

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.

Biologic Agents In Systemic Dermatotherapy: Cutaneous And Systemic Side Effects.

The recent significant breakthroughs in the understanding of the pathogenetic mechanisms of psoriasis and other immune-mediated inflammatory disorders, have led to the emergence of a wide array of biologic agents or biologics, that are especially designed to target selective intracellular or extracellular components and pathways of the dysregulated immune response. These targeted biologic agents have altered the landscape in dermatotherapy aiming to offer higher therapeutic efficacy and an alternative in patients who either failed on conventional systemic regimens or have no other therapeutic options. In the last two decades, the number of the commercially available biologic agents and the extent of their use have dramatically increased; today, these compounds represent a substantial part of modern dermatologic armamentarium. Due to the immunosuppressive potential of biologics, serious concerns were raised about their safety profile, already during the pre-approval period. These concerns did not subside after the incorporation of the postmarketing experience, particularly after the withdrawal of a biologic agent (efalizumab) due to its serious and even fatal side effects. The purpose of the present article is to review the cutaneous and systemic side effects of all biologic agents used so far in modern systemic dermatotherapy and to contribute to a better and updated awareness of their safety risks among clinicians, which will enable the latter to make the best informed and personalized drug selection and therapeutic decisions. This review was mainly based on data derived from Medline and Scopus databases and from manufacturing companies, as well.

Erythema multiforme following pneumococcal vaccination.

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.

Classic form of eosinophilic pustular folliculitis in an immunocompetent girl: rapid and complete resolution after low-dose oral indomethacin treatment.

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.