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Dermatology Online Journal Aug 2009A 21-year-old man presented with a life-long history of diffusely thickened skin with a grainy-to-ridged surface, verrucous perioral plaques with radial fissures, and...
A 21-year-old man presented with a life-long history of diffusely thickened skin with a grainy-to-ridged surface, verrucous perioral plaques with radial fissures, and diffuse palmoplantar keratoderma with a stippled appearance. These skin findings were accompanied by sensorineural hearing loss and keratoconjunctivitis, a clinical triad diagnostic of keratitis-ichthyosis-deafness (KID) syndrome. The patient also had a history of recurrent infections and cysts on the scalp. This report draws attention to inflammatory nodules (representing ruptured folliculitis), cysts, and recurrent infections on the scalp as manifestations of KID syndrome and reviews the increasingly recognized risk of follicular tumors and squamous-cell carcinomas in patients with this conditions.
Topics: Deafness; Humans; Ichthyosis; Keratitis; Male; Syndrome; Young Adult
PubMed: 19891919
DOI: No ID Found -
Life (Basel, Switzerland) Sep 2023Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic inflammatory disease that manifests as painful nodules, abscesses, draining dermal tunnels, and... (Review)
Review
Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic inflammatory disease that manifests as painful nodules, abscesses, draining dermal tunnels, and scarring in intertriginous areas such as the axillae, groin, and breasts. The nature of the disease and its chronicity have a destructive impact on mental health and quality of life. HS has an estimated global prevalence of 0.00033-4.1% and it disproportionately affects females compared to males. HS involving the female anogenital regions is reported rarely in the gynecological literature, and it can often be mistaken for other vulvar diseases. The distinct phenotypes and HS rarity cause delayed diagnosis and the implementation of effective treatment. Acne inversa is associated with several comorbidities, including metabolic disease, diabetes mellitus, inflammatory bowel diseases, and spondyloarthropathies. Although HS etiology and pathogenesis remain unclear, studies have shown that lifestyle, immunological processes, genetics, and hormonal predispositions may promote follicular hyperkeratosis, dilatation, and rupture, leading to the development of chronic tissue inflammation. This article provides updated information on HS pathogenesis, comorbidities, and treatment methods. Furthermore, we share our experience in the surgical treatment of the disease, which often proves most effective, and highlight that an interdisciplinary management approach ensures optimal outcomes.
PubMed: 37763299
DOI: 10.3390/life13091895 -
Skin Appendage Disorders Aug 2023Disease severity assessment tools play a large part in evaluating skin conditions in dermatology. Currently, there is no existing validated assessment tool for keratosis... (Review)
Review
Disease severity assessment tools play a large part in evaluating skin conditions in dermatology. Currently, there is no existing validated assessment tool for keratosis pilaris (KP), a benign yet highly prevalent follicular disorder. A range of proposed scoring tools have been used in different clinical trials for the assessment of potential treatments for KP. A literature review of the current scoring systems used for KP shows that there is a lack of consistency with most studies using varying versions of unvalidated investigator global assessment (IGA) scores and quartile grading systems. A review of these studies shows that current methods of evaluating KP in clinical trials are subjective, unreliable, and inconsistent. A standardised and validated scoring system would be significant as it could be used in clinical trials to advance the current knowledge of KP.
PubMed: 37564689
DOI: 10.1159/000529487 -
The Journal of Investigative Dermatology Dec 2021Pachyonychia congenita (PC) is a genetic disorder of keratin that presents with nail dystrophy, painful palmoplantar keratoderma, and other clinical manifestations. We...
Pachyonychia congenita (PC) is a genetic disorder of keratin that presents with nail dystrophy, painful palmoplantar keratoderma, and other clinical manifestations. We investigated the genotype‒structurotype‒phenotype correlations seen with mutations in keratin genes (keratin [K]6A, K6B, K6C, K16, K17) and utilized protein structure modeling of high-frequency mutations to examine the functional importance of keratin structural domains in PC pathogenesis. Participants of the International PC Research Registry underwent genetic testing and completed a standardized survey on their symptoms. Our results support previous reports associating oral leukokeratosis with K6A mutations and cutaneous cysts, follicular hyperkeratosis, and natal teeth with K17 mutations. Painful keratoderma was prominent with K6A and K16 mutations. Nail involvement was most common in patients with K6A mutation and least common in those with K6C mutation. Across keratin subtypes, patients with coil 2B mutations had the greatest impairment in ambulation, and patients with coil 1A mutations reported more emotional issues. Molecular modeling demonstrated that hotspot missense mutations in PC largely disrupted hydrophobic interactions or surface charge. The former may destabilize keratin dimers/tetramers, whereas the latter likely interferes with higher-order keratin filament formation. Understanding the pathologic alterations in keratin structure improves our knowledge of how PC genotype correlates with clinical phenotype, advancing insight into disease pathogenesis and therapeutic development.
Topics: Genetic Association Studies; Humans; Keratin-16; Keratin-17; Keratin-6; Keratins; Models, Molecular; Mutation; Pachyonychia Congenita
PubMed: 34116063
DOI: 10.1016/j.jid.2021.03.035 -
The Journal of Dermatological Treatment Dec 2023Lichen planopilaris (LPP) is a lymphocytic primary cicatricial alopecia characterized by perifollicular erythema, follicular hyperkeratosis and scaring, resulting in...
Lichen planopilaris (LPP) is a lymphocytic primary cicatricial alopecia characterized by perifollicular erythema, follicular hyperkeratosis and scaring, resulting in permanent hair loss. Current treatment modalities, both topical and systemic, fail to achieve satisfactory and consistent results. As therapies fail to halt the inflammatory process, patients with LPP may face long-term disfigurement and significant psychological burden. To initiate an efficacious targeted therapy with good tolerability and low side effect profile that will allow hair regrowth and prevent the development to disfiguring alopecia. Here, we report on a case of rare LPP in a linear distribution (LLPP) involving the scalp and forehead failing to achieve satisfactory results with continued hair loss with multiple previous treatments. Complete hair regrowth was achieved 12 weeks after treatment with an anti-psoriatic, anti-interleukin (IL)-17A/F antibody (Taltz, Ixekizumab, Lilly). Patient continued to display sustained efficacy with no reported side effects until 12 months on treatment. The present case underlines the viability of Ixekizumab as a possible first-line, targeted therapy for LPP and its variants with sustained efficacy. Multicenter trials are warranted to confirm the benefit of Ixekizumab as a successful targeted biologic treatment option for LPP and LLPP.
Topics: Humans; Alopecia; Hair; Lichen Planus; Antibodies, Monoclonal, Humanized; Dermatologic Agents; Treatment Outcome
PubMed: 37026832
DOI: 10.1080/09546634.2023.2201364 -
American Journal of Transplantation :... Apr 2019Face vascularized composite allografts (FVCAs) have helped patients with severe facial disfigurement, with acute rejection now largely controlled through iatrogenic...
Face vascularized composite allografts (FVCAs) have helped patients with severe facial disfigurement, with acute rejection now largely controlled through iatrogenic immunosuppression. However, little is known regarding the incidence and mechanism(s) of more long-term pathologic alterations in FVCAs that may affect function and graft durability. Protocol surveillance biopsy specimens for up to an 8-year interval in 7 patients who received FVCAs at our institution revealed histopathologic evidence of chronic rejection. Clinical manifestations included features of premature aging, mottled leukoderma accentuating suture lines, telangiectasia, and dryness of nasal mucosa. Pathologic changes consisted of epidermal thinning accompanied by discrete foci of lymphocyte-mediated cytotoxicity, hyperkeratosis, follicular plugging, vascular ectasia, and sclerosis beneath the epidermal layer associated with collagen type I deposition. Genomic interrogation and immunohistochemistry of sclerotic zones revealed upregulation of the AP-1 pathway components, JunB and c-Fos, previously implicated in overproduction of type I dermal collagen in the setting of systemic sclerosis. We conclude that some patients develop chronic rejection in FVCAs with striking similarities to alterations seen in certain autoimmune cutaneous disorders (lupus erythematosus and scleroderma/chronic sclerodermoid graft-versus-host disease). Identification of relevant pathways and genes, such as JunB and c-Fos, may provide new targets for preventative therapies for chronic immune-mediated changes in vascularized composite allografts.
Topics: Adult; Chronic Disease; Composite Tissue Allografts; Facial Transplantation; Female; Gene Expression Profiling; Graft Rejection; Humans; Immunosuppressive Agents; Male; Middle Aged
PubMed: 30312535
DOI: 10.1111/ajt.15143 -
Orphanet Journal of Rare Diseases May 2011The IFAP syndrome is a rare X-linked genetic disorder reported in nearly 40 patients. It is characterized by the triad of Ichthyosis Follicularis, Alopecia, and... (Review)
Review
The IFAP syndrome is a rare X-linked genetic disorder reported in nearly 40 patients. It is characterized by the triad of Ichthyosis Follicularis, Alopecia, and Photophobia from birth. Other features such as short stature, intellectual disability, and seizures may develop in the first few years of life. Skin histopathology is non-specific and consists of dilated hair follicles with keratin plugs extending above the surface of the skin, decreased or absent sebaceous glands, and decreased desmosomes in number and size. The disorder results from mutations in the MBTPS2 gene that impairs cholesterol homeostasis and the ability to cope with endoplasmic reticulum stress. Follicular hyperkeratosis can be treated using topical keratolytics, emollients and urea preparations. A moderate response to acitretin therapy has been noted in some patients. Intensive lubrication of the ocular surface is essential. Life expectancy in patients with IFAP syndrome can vary from death in the neonatal period to normal surviving. Cardiopulmonary complications remain the major cause of death.
Topics: Acitretin; Alopecia; Humans; Ichthyosis; Keratolytic Agents; Mutation; Photophobia
PubMed: 21600032
DOI: 10.1186/1750-1172-6-29 -
JAAD International Jul 2020The pathogenic model of hidradenitis suppurativa is in the midst of a paradigm shift away from a disorder of primary follicular occlusion to an autoinflammatory... (Review)
Review
The pathogenic model of hidradenitis suppurativa is in the midst of a paradigm shift away from a disorder of primary follicular occlusion to an autoinflammatory keratinization disease. Observational, experimental, and therapeutic evidence supports the concept of hidradenitis suppurativa as a primarily inflammatory disorder, a disorder of autoimmunity, or both, in contrast to the current prevailing paradigm of primary follicular occlusion. The lack of reliable and high-fidelity disease models has limited the available experimental and mechanistic evidence to support or refute one pathogenic model over another. This scholarly review synthesizes the existing clinical, histologic, and molecular data to evaluate the extant evidence supporting the autoinflammatory paradigm and further informing the molecular mechanisms of hidradenitis suppurativa pathogenesis. Follicular hyperkeratosis/occlusion and perifollicular inflammation coexist in histologic specimens, with interleukin 1α demonstrated to stimulate comedogenesis in the infundibulum. pH elevation in occluded body sites alters the microbiome and amplifies existing T-helper cell type 17 immunoresponses. Known metabolic comorbidities and smoking are known to upregulate interleukin 1α in follicular keratinocytes. Identified genetic variants may alter epidermal growth factor receptor signaling, leading to upregulated keratinocyte inflammatory responses. The process of follicular rupture and dermal tunnel formation can be explained as secondary responses to inflammatory activation of fibroblasts and epithelial-mesenchymal transition, with antibody production associated with inflammatory amplification in advanced disease. This review aims to reevaluate and integrate the current clinical, histologic, and molecular data into a pathogenic model of hidradenitis suppurativa. This is essential to advance our understanding of the disease and identify novel therapeutic targets and approaches.
PubMed: 34409324
DOI: 10.1016/j.jdin.2020.05.005 -
Pediatric Rheumatology Online Journal May 2024Vitamin C deficiency, or scurvy, is rare but poses risks for children with poor diets, limited resources, or malabsorption issues. It may also be common in children with...
BACKGROUND
Vitamin C deficiency, or scurvy, is rare but poses risks for children with poor diets, limited resources, or malabsorption issues. It may also be common in children with restrictive or selective dietary habits in children with global developmental delay, autism spectrum disorder, and physical disabilities. Symptoms include fatigue, irritability, joint and muscle pain, joint swellings, edema, swollen gums, easy bruising, and delayed wound healing. Early recognition and prompt intervention are essential to prevent the progression of symptomatic vitamin C deficiency in children.
CASE PRESENTATION
We present a case of a 13-year-old boy with developmental delay secondary to Lennox Gastaut syndrome referred for suspected recurrent, severe, and atypical IgA vasculitis. He presented with irritability, loss of appetite, petechial and ecchymotic lower limb lesions, unilateral gum swelling, severe arthritis, peripheral oedema, severe weight loss, anaemia, and raised inflammatory markers. Multiple investigations were performed before the diagnosis of scurvy was made. A surgical finding of friable gingival tissue with multiple loose teeth, a skin biopsy with follicular hyperkeratosis and extravasated perifollicular red blood cells, and a typical X-ray finding led to the diagnosis of scurvy.
CONCLUSION
Scurvy should be given careful consideration as a differential diagnosis in patients presenting with musculoskeletal issues, mucocutaneous complaints, and constitutional symptoms such as malaise, asthenia, irritability, and loss of appetite. A focused and detailed dietary history looking for a lack of good sources of vitamin C can be an easy indicator of this differential. Imaging studies revealing the typical features can also help make the diagnosis. Pathology of the skin revealing pathognomonic features can add to the certainty of the diagnosis. In the absence of all else, the rapid response to treatment with an appropriate dose of vitamin C has a diagnostic and therapeutic role.
Topics: Humans; Scurvy; Male; Adolescent; Diagnosis, Differential; Ascorbic Acid; IgA Vasculitis
PubMed: 38760753
DOI: 10.1186/s12969-024-00992-2 -
The Journal of Investigative Dermatology Mar 1987The stratum corneum lipids, responsible for the epidermal water barrier, consist principally of ceramides, cholesterol, cholesteryl sulfate, and free fatty acids. These...
The stratum corneum lipids, responsible for the epidermal water barrier, consist principally of ceramides, cholesterol, cholesteryl sulfate, and free fatty acids. These lipids are arranged in multiple intercellular lamellae that provide an efficient water barrier because of the crystalline array of the straight and predominantly saturated lipid chains. Interlamellar linkages provided by lipids based on 30-carbon omega-hydroxyacids may be responsible for holding together the intercellular lamellae as well as for assembly of the lamellar granules of the granular cells. The normally ordered exfoliation of corneocytes as they arrive at the surface seems to require hydrolysis of the cholesteryl sulfate to free cholesterol. The sebaceous glands secrete continuously, producing sebum that consists predominantly of triglycerides, wax esters, and squalene. High rates of sebum production per sebocyte result in low levels of linoleate in the sebaceous esters, subjecting the follicular epithelium to essential fatty acid deficiency and the characteristic hyperkeratosis that results in comedo formation. Suppression of sebum production by drugs elevates sebum linoleate concentration and relieves follicular hyperkeratosis. Thus, sebum continues to be a prime suspect in the crime of acne. Low levels of sebaceous gland activity are not correlated with the occurrence of dry skin.
Topics: Acne Vulgaris; Body Water; Cell Differentiation; Dermatology; Epidermal Cells; Humans; Lipids; Sebaceous Glands; Sebum; Skin; Skin Diseases
PubMed: 2950180
DOI: 10.1111/1523-1747.ep12468850