Dermal microdialysis: A method to determine drug levels in the skin of patients with Post kala-azar dermal leishmaniasis (PKDL).

OBJECTIVES: Post-kala-azar-dermal leishmaniasis (PKDL) is an infectious skin disease that occurs as sequela of visceral leishmaniasis (VL) and causes cutaneous lesions on the face and other exposed body parts. While the first-line drug miltefosine is typically used for 28 days to treat VL, 12 weeks of therapy is required for PKDL, highlighting the need to evaluate the extent of drug penetration at the dermal site of infection. In this proof-of-concept study, we demonstrate the use of a minimally invasive sampling technique called microdialysis to measure dermal drug exposure in a PKDL patient, providing a tool for the optimization of treatment regimens. METHODS AND MATERIALS: One PKDL patient receiving treatment with miltefosine (50 mg twice daily for 12 weeks) was recruited to this proof-of-concept study and consented to undergo dermal microdialysis. Briefly, a µDialysis Linear Catheter 66 for skin and muscle, a probe with a semi-permeable membrane, was inserted in the dermis. A perfusate (a drug-free physiological solution) was pumped through the probe at a low flow rate, allowing miltefosine present in the dermis to cross the membrane and be collected in the dialysates over time. Protein-free (dialysates) and total (blood and skin biopsies) drug concentrations were analysed using LC-MS/MS. RESULTS: and conclusions: Using microdialysis, protein-free miltefosine drug concentrations could be detected in the infected dermis over time (Cmax ≈ 450 ng/ml). This clinical proof-of-concept study thus illustrates the potential of dermal microdialysis as a minimally invasive alternative to invasive skin biopsies to quantify drug concentrations directly at the pharmacological site of action in PKDL.

Acquired Lymphangiectasia of the Scrotum.

A 56-year-old man presented with multiple, skin-colored, raised eruptions of the scrotum that had been present for 2 years. Their onset had been gradual, and they had been increasing in size, resulting in cosmetic disfigurement. A year previously, he had been operated on for a bilateral vaginal hydrocele with partial excision and eversion of the sac (Jabouley method).1 There had been no extramarital or unprotected sexual contact, other hospitalizations, or major surgery, swelling of the legs, or long periods of incumbency. Cutaneous examination revealed multiple, discrete and/or coalescing verrucous papules distributed on the upper portion of the scrotum and associated with edema of the penis (Figure 1). The inguinal lymph nodes were not enlarged. Complete blood counts and ultrasonography of the abdomen were normal. Tissue sections stained with hematoxylin and eosin showed hyperkeratosis and multiple ectatic vessels, primarily confined to the papillary dermis, abutting the overlying epidermis, and demarcated by a single endothelial lining. The dilated vessels contained homogenous eosinophillic material (Figure 2).

Tuberous Sclerosis Complex: A Classic Presentation.

An 11-year-old girl presented with an insidiously evolving, reddish-brown, small, hard, elevated lesion, occupying the midsection of her face, which had been present since early childhood. There were also a few small white spots over the trunk. There was no history of seizures or visual deficit, and no burning on exposure to sunlight. There were no known congenital defect noted at birth, and her parents were nonconsanguineous. There was no significant family history. There were numerous 2- to 4-mm reddish-brown papules located symmetrically on the nose, nasolabial folds, and cheeks (Figure 1A). In addition, there was an uneven 3-cm plaque in the lumbosacral region that resembled orange peel-a shagreen patch (Figure 1B). There were also two well-defined, 5- to 10-mm, hypomelanotic, ivory-white macule(s) with irregular margins (Figure 1C). The buccal mucosa and nails were unremarkable, and indirect ophthalmoscopic and slitlamp examination of the eye was normal. Laboratory studies were unremarkable. Ultrasonography of the abdomen was normal, as were abdominal and chest x-rays.

Unna Nevus: Early Presentation in a 10-Year-Old Girl.

A 10-year-old girl presented with three asymptomatic raised lesions over the dorsal aspect of her left index finger present for the past 7 years. On examination, there were three skin-colored nodules overlying the middle and distal phalanx of her left index finger, without any attachment to the underlying structures (Figure 1) The nodule over the distal phalanx was the largest with a cobblestone-like surface. All the nodules were firm to touch. Cutaneous, mucosa, hair, nails, and systemic examinations were within normal limits. The two smaller nodules were excised under local anesthesia and sent for histopathologic examination. Histologic study from one of the representative lesion showed type B nevus cells (lymphocytoid), located in the expanded papillary dermis (Figures 2 and 3).

Twenty-Nail Dystrophy and Darier's (Darier-White) Disease.

A 35-year-old married man presented with progressive distortion of all the nails of the hands and toes for the past 30 years. Initially, his parents noticed yellowish discoloration and roughness of the thumb nail at the age of 5 years. Since then, the changes have been insidious to involve the other nails. Currently, the nails are lusterless, rough, ridged, and difficult to trim. In addition, the patient has had dark, dirty-looking raised eruptions over the skin, attended by generalized itching, corresponding to the onset of the nail lesions. His mother experienced similar disease. Examination of the nails was marked by alternating elevation and depression (ridging) and/or pitting, lack of luster, roughening, sandpaper texture, and splitting, along with muddy, grayish white discoloration. Dystrophy of the nails was prominent. The changes were bilateral and symmetrical, affecting all 10 fingers and 10 toes (Figure 1).

Basal cell carcinoma: pathophysiology.

Basal cell carcinoma (BCC) is the most common skin cancer in humans, which typically appears over the sun-exposed skin as a slow-growing, locally invasive lesion that rarely metastasizes. Although the exact etiology of BCC is unknown, there exists a well-established relationship between BCC and the pilo-sebaceous unit, and it is currently thought to originate from pluri-potential cells in the basal layer of the epidermis or the follicle. The patched/hedgehog intracellular signaling pathway plays a central role in both sporadic BCCs and nevoid BCC syndrome (Gorlin syndrome). This pathway is vital for the regulation of cell growth, and differentiation and loss of inhibition of this pathway is associated with development of BCC. The sonic hedgehog protein is the most relevant to BCC; nevertheless, the Patched (PTCH) protein is the ligand-binding component of the hedgehog receptor complex in the cell membrane. The other protein member of the receptor complex, smoothened (SMO), is responsible for transducing hedgehog signaling to downstream genes, leading to abnormal cell proliferation. The importance of this pathway is highlighted by the successful use in advanced forms of BCC of vismodegib, a Food and Drug Administration-approved drug, that selectively inhibits SMO. The UV-specific nucleotide changes in the tumor suppressor genes, TP53 and PTCH, have also been implicated in the development of BCC.

Origin and evolution of syphilis: drifting myth.

The venereal form of treponematosis, caused by the spirochete Treponema pallidum, plagued every major city in the preantibiotic era. "Civilization means syphilization," was an idea touted by Richard von Krafft-Ebing in the late 19th, and early 20th centuries that the effects of modern life make men more susceptible to syphilis and other diseases. Christopher Columbus was thought of as an importer of syphilis to Europe. Because his serendipitous voyages to the New World initiated the process of Spanish colonization, which foreshadowed general European colonization of the New World, it is difficult to rule out the cultural and political animosity created by Columbus and his men. These recent revelations are intriguing and may create dialogue that may subsequently challenge the age-old theory of "East to West" spread of venereal syphilis. This contribution warrants the continuation of study in this direction, taking into account skeletal studies that utilized radiocarbon dating technique and the phylogenetic analysis of the bacterial strains, offering a possible consensus on the origin and evolution of syphilis.

"Storage, Backup and Archiving of Images"- E-Dermatology Task Force (IADVL Academy).

Dermatology is a specialty that relies a lot on the visual aspect of clinical diagnosis. Taking photographs of skin lesions is a routine part of clinical practice. They are used to document skin changes during the course of treatment. It is useful for publishing articles in academic journals and textbooks, and serves as a teaching aid. Images are an important form of patient data. Like all patient data, the need for ensuring confidentiality and security is of paramount importance. Keeping all this in mind, it is important to know how to store, backup and archive your images in a safe and efficient manner.

Informed Consent in Biomedical Research: Scopes and Challenges.

Medical science is evolving constantly and this evolution cannot happen without biomedical research involving human participant. Owing to a tumultuous history, importance of ethical research cannot be over emphasized in today's world and the concept of informed consent becomes the guardian of ethics, not only to improve the bonding between the participant and researcher aiding a wholehearted involvement but also ensuring safety for the participants from research related injury/loss. Subject information sheet (SIF) and Informed consent form (ICF) are the fundamental elements of informed consent document. Process of obtaining them from illiterate and vulnerable populations involves the legally authorized representative (LAR) and impartial witness. Audiovisual recording becomes important in case of clinical trials. Process of obtaining informed consent becomes challenging for vulnerable populations as well as during pandemic situations. A comprehensive informed consent is essential for a credible and ethical research.

Cutaneous Cysts with Nail Dystrophy in a Young Female: A Classical Association.

Pachyonychia Congenita (PC) refers to a group of autosomal dominant disorders with variable clinical presentations. While nail dystrophy and plantar keratoderma are the most consistent features in all the variants, a myriad of other manifestations has been observed. This report highlights a case of young female presenting with multiple asymptomatic cutaneous cysts associated with plantar kearatoderma and nail dystrophy. Similar nail changes were evident in her son also. Such clinical presentation, in corroboration with histopathological evaluation of the cutaneous cyst prompted us to make a diagnosis of Pachyonychia Congenita type II.

The Bumpy Face of Che Guevara: An Interesting Case.

Placement of decorative tattoo on the skin may lead to various immunological, infective, and coincidental complications. Inoculation of human papillomavirus leading to development of verruca is an uncommon complication of tattoos. The present report highlights the development of verruca vulgaris, developing after 2 years of tattooing in a young male.

Atopic Dermatitis: Clinical Connotations, Especially a Focus on Concomitant Atopic Undertones in Immunocompromised/Susceptible Genetic and Metabolic Disorders.

Atopic dermatitis (AD) is an intriguing clinical entity. Its clinical connotations are varied, the updates of which are required to be done periodically. An attempt to bring its various facets have been made highlighting its clinical features keeping in view the major and the minor criteria to facilitate the diagnosis, differential diagnosis, complications, and associated dermatoses. The benefit of the current dissertation may percolate to the trainees in dermatology, in addition to revelations that atopic undertones in genetic susceptibility and metabolic disorder may provide substantive insight for the future in the understanding of thus far enigmatic etiopathogenesis of AD.

Atopic Dermatitis: A Cross-Sectional (Descriptive) Study of 100 Cases.

BACKGROUND: Atopic dermatitis is a distinct age-related clinical entity. Its etiopathogenesis is largely insubstantial. Nevertheless, it seems to be an outcome of interplay of maternal and inheritance, pregnancy/intrauterine and environmental factors. Besides, immune dysregulation, and nutritional supplements also play essential roles. Its diagnosis has been perpetuated by three or more major/minor criteria. OBJECTIVES: An endeavor to study its demographic and clinical pattern in contemporary prospective. MATERIALS AND METHODS: 100 fresh patients of atopic dermatitis, diagnosed on the basis of an established three or more major and minor criteria, salient presentations of which were recorded in a preset proforma, which also recorded age, duration, age of onset, and sex. Serum immunoglobulin E (IgE) levels were determined by conventional technique. The data thus obtained was analysed to study its clinical pattern and to correlate its severity to IgE levels. RESULTS: Its overall (new and old) prevalence was 0.98%, while that of new patients was 0.24%. 83 (83%) were in the age group of 2-12 years, of which 54 (83.1%) were males and 29 (82.9%) were female, of which 70 (70%) had urban, while 30 (30%) had rural background. Its duration varied from 8 to 192 weeks, with a mean of 76 weeks, and a standard deviation of 21.42 weeks [76 ± 21.42]. CONCLUSION: Atopic dermatitis is a discrete, overt, age and IgE-related entity frequently displaying varying demographic and clinical connotation.