Contact Dermatitis:
Contact dermatitis is a common inflammatory skin condition characterized by erythematous and pruritic skin lesions that occur after contact with a foreign substance. There are two forms of contact dermatitis: irritant and aller- gic. Irritant contact dermatitis is caused by the non–immune-modulated irritation of the skin by a substance, leading to skin changes. Allergic contact dermatitis is a delayed hypersensitivity reaction in which a foreign substance comes into contact with the skin; skin changes occur after reexposure to the substance.
Allergic contact dermatitis is a delayed hypersensitivity reaction in which a foreign substance comes into contact with the skin; skin changes occur with reexposure. Allergic contact dermatitis is caused by a type IV, T cell–mediated, delayed hypersensitivity reaction in which a foreign substance comes into contact with the skin and is linked to skin protein, forming an antigen complex that leads to sensitization. Upon reexposure of the epidermis to the antigen, the sensitized T cells initiate an inflammatory cascade, causing the skin changes associated with allergic contact dermatitis.
Common substances that cause contact dermatitis include poison ivy, nickel, and fragrances.
Allergic contact dermatitis is a common eczematous skin disease that occurs in sensitized individuals at the site of contact with small chemicals penetrating the skin barrier. The onset of the disease is mostly due to the rapid recruitment of chemical-specific CD8+ T cells, which induce apoptosis of keratinocytes. Additionally, CD4+ Th1 and Th17 contribute to the extension of the inflammatory reaction by releasing pro-inflammatory cytokines that activate keratinocytes and other skin resident cells. The immune reaction is tightly regulated through multiple mechanisms. In particular, T cell population with regulatory function, such as T regulatory cells 1 and CD4+CD25+ T regulatory cells have a critical role in preventing the development of allergic reactions to innocuous chemicals contacting the skin, and in limiting the magnitude of the inflammatory process in already sensitized individuals. Allergic contact dermatitis is a chronic disease, which lasts, in most cases, for the entire life of the affected individual. Thus, prevention and avoidance of contact with the sensitizer are critical factors in the management of affected patients.
The gold standard therapeutic approach for the disease remains the local and/or systemic immunosuppression, aimed to block T cell functions and keratinocyte responsiveness to pro-inflammatory stimuli. Localized acute allergic contact dermatitis lesions are successfully treated with mid- or high-potency topical steroids, such as triamcinolone 0.1% (Kenalog, Aristo- cort) or clobetasol 0.05% (Temovate).
Eczema is an umbrella term for different kinds of skin inflammation. It is marked by dry, reddened skin that itches or burns. When skin becomes dry and irritated in winter, eczema can flare. Stay one step ahead by moisturizing frequently with an oil-based ointment that contains sunscreen. Sweating and overheating can also trigger the itch/scratch cycle, so dress in easy-to-peel-off layers.
Atopic dermatitis (AD):
Atopic dermatitis (AD) is a common chronic, pruritic inflammatory skin condition. AD is most commonly treated with topical corticosteroids. Atopic dermatitis (AD), included in the eczema/ dermatitis group, is a skin disorder characterized by chronic inflammation and pruritus. The number of AD patients is increasing, especially in developed countries. AD affects people of all ages, and its prevalence in children worldwide is reported to be as high as 20%. Another study reported that dermatologic patients applied only 35% of the expected individualized dosages on average, so the dose of topical steroid is critical information for patients. (Yamaura, “A survey on awareness of the “finger-tip unit” and medication guidance for the use of topical steroids among community pharmacists” Drug Discoveries & Therapeutics. 2019; 13(3):128-132).
Cutibacterium acnes (P. acnes):
Introduction: The skin commensal Propionibacterium acnes, recently renamed Cutibacterium acnes, along with the other major pathophysiological factors of increased seborrhea, hyperkeratinization of the pilosebaceous unit, and inflammation, has long been implicated in the pathogenesis of acne. Acnes biofilms are more frequent in acne, and different phylotypes may induce distinct immune responses in acne. P. acnes plays a further important role in the homeostasis of the skin’s microbiome, interacting with other cutaneous commensal or pathogenic microorganisms such as Staphylococcus epidermidis, Streptococcus pyogenes, and Pseudomonas species.
Recently, a taxonomic reclassification was proposed in which P. acnes was renamed Cutibacterium acnes to account for genomic adaptive changes and to differentiate
it from other Propionibacteria species. In particular, specific lipase genes were identified encoding for triacylglycerol lipase and lysophospholipase able to degrade sebum lipids. However, it has been proposed that it is taxonomically valid to continue to use the genus name Propionibacterium for the cutaneous group within dermatology specialties for a range of different reasons, including to avoid confusion with the previous name, Corynebacterium acnes. See Dessinioti
P. acnes has been regarded as an important member of the cutaneous microbiota. It has been linked to the inflammatory skin condition acne vulgaris for more than 100 years. The four
major pathophysiological factors implicated in the pathogenesis of acne include the role of P. acnes, increased seborrhea, hyperkeratinization of the pilosebaceous unit, and inflammation. P. acnes colonization of the skin is necessary but not sufficient for the establishment of acne pathology. P. acnes dominates the microbiota of pilosebaceous units and accounts for 87% of
clones in patients with acne and in individuals without acne. See Dessinioti
Structure: P. acnes is a Gram-positive, non-spore-forming human skin commensal that prefers anaerobic growth condition. It is a member of the normal skin microbiota along with P. avidum, P. granulosum, and P. humerusii. The P. acnes genome is 2.5 Mb in size and has been completely sequenced. It has genes encoding metabolic enzymes, enabling it to survive in microaerophilic conditions, but also lipases that degrade the lipids of the pilosebaceous follicle, providing the bacterium with the energy it needs. See Dessinioti
Pathology:
P. acnes shows complex interactions with key events implicated in the pathogenesis of acne. It interacts with the innate immunity, including Toll-like receptors (TLRs), antimicrobial peptides (AMPs), protease-activated receptors (PARs), and matrix metalloproteinase (MMP), and upregulates the secretion of pro-inflammatory cytokines, including interleukin-1a (IL-1a),
IL-1β, IL-6, IL-8, IL-12, tumor necrosis factor-alpha (TNF-α), and granulocyte-macrophage colony-stimulating factor (GMCSF), by human keratinocytes, sebocytes, and macrophages.
P. acnes extracts are directly able to modulate the differentiation of keratinocytes by inducing b1, a3, a6s, aVb6 integrin expression, and filaggrin expression on keratinocytes, changes seen in the development of acne lesions. Hyaluronic acid (HA) lyase is a ubiquitous enzyme with two
distinct variants in the P. acnes population that differ in their ability to degrade HA and could be involved in the pro-inflammatory responses seen in acne.
Skin Microbiome:
Apart from its target activities in acne, P. acnes has an intriguing role in the homeostasis of the skin’s microbiome, interacting with other cutaneous microorganisms such as Staphylococcus
epidermidis, Streptococcus pyogenes, and Pseudomonas species. In the microbiome of healthy skin, S. epidermidis may limit the overcolonization with P. acnes strains and reduce P. acnesinduced IL-6 and TNF-α production by keratinocytes. On the other hand, P. acnes may limit the proliferation of S. aureus and S. pyogenes by promoting triglyceride hydrolysis and
propionic acid secretion. As a result, an acidic pH is maintained in the pilosebaceous follicle. A change of the microbiome composition may lead to a disturbed skin barrier and inflammation. In acne, a modified profile of P. acnes is noticed; different phylotypes differ between patients with and without acne.
Treatment:
The antibiotic resistance of P. acnes is a worldwide problem, and rates of resistance increased from 20% in 1979 to 64% in 2000; rates for tetracyclines were lower compared with rates for
clindamycin and erythromycin.
Scleroderma:
Scleroderma is a rare autoimmune disease that causes the body to produce too much collagen, leading to hardened and tight skin and connective tissue.
Symptoms: can vary from localized ahrdening of the skin to systemic involvement of itnernal organs like the heart, lungs, and kidneys.
Early signs of scleroderma often include Raynaud’s phenomenon, which causes fingers and toes to become pale, numb, or tingly in response to cold or stress.
The most visible symptom is thickened, tight skin, but it can also lead to dryness, itchiness, sores, and changes in skin color.
–Digital Ulcers: are painful, open sores on a finger or tow that can be difficult to heal. These ulcers often occur in people with systemic sclerosis and Raynaud’s phenonmenon due to poor blood flow to the digits, but can also develop from other causes like trauma or diabetes. Symptoms of a dveloping ulcer can include warmth, redness, and tingling, and it requries prompt and proper wound care to prevent infection and further damage.
–Sclerosis: is the general medical term for hardening of tissues, while scleroderma is a specific disease characterized by this hardening, often in the skin.
Pathology:
Vitiligo:
Introduction: Vitiligo is an autoimmune disease of the skin that targets pigment-producing melanocytes and results in patches of depigmentation that are visible as white spots.
Pathology: Recent research studies have yielded a strong mechanistic understanding of this disease.
–Autoreactive cytotoxic CD8+ T cells engage melanocytes and promote disease progression through the local production of IFN-γ, and IFN-γ-induced chemokines are then secreted from surrounding keratinocytes to further recruit T cells to the skin through a positive-feedback loop.
—IFN-gamma: Regarding the mechanisms by which CD8+ T cells cause vitiligo, their production of the cytokine IFN-γ is central to disease. Consistent with mouse studies that demonstrated the functional significance of IFN-γ to vitiligo, disruption of IFN-γ signaling by Janus kinase ( JAK) inhibitors contributes to repigmentation of human vitiligo patients. IFN-γ signals by binding to its cell surface receptor (IFNgR), which forms a heterodimeric protein complex in the presence of IFN-γ that activates gene transcription
hrough associated JAKs. There are four members of the JAK family ( JAK1, JAK2, JAK3, TYK2),
and inhibitors directed at several combinations of these kinases are being tested as new treatments for many human diseases (83). The IFNgR signals through JAK1 and JAK2, and inhibition of either JAK1 or JAK2 reduces IFN-γ signaling. The first two JAK inhibitors approved for human use, ruxolitinib and tofacitinib, both reduce IFNgR signaling by targeting JAK1/2 (ruxolitinib) or JAK1/3 (tofacitinib). (Annual Review of Immunology “Vitiligo: Mechanisms of Pathogenesis and Treatment” Michael L. Frisoli, Kingsley Essien, and John E. Harris)
Vitiligo usually appears in patients before the age of 30 years, and since it rarely regresses spontaneously, it enables close observation of the disease and its progression over decades. This visibility as well as its high incidence and ready access to affected tissues have enabled detailed study of vitiligo through translational research approaches over decades, providing a strong foundation for modern studies to determine detailed mechanisms of pathogenesis. Annual Review of Immunology “Vitiligo: Mechanisms of Pathogenesis and Treatment” Michael L. Frisoli, Kingsley Essien, and John E. Harris)
Unlike most autoimmune diseases, vitiligo is fully reversible. Vitiligo primarily destroys the
pigment-producing cells, melanocytes, located in the epidermis between the hair follicles (interfollicular epidermis). However, the disease commonly spares melanocytes residing within the hair follicle because of immune privilege at this site, similar to other privileged sites that contain melanocytes, such as the brain, eye, and inner ear. Hair follicles also contain melanocyte stem cells that are capable of repopulating the epidermis of vitiligo lesions with functional, newly differentiated melanocytes that possess the capacity to restore normal pigmentation. Thus, clinical repigmentation of vitiligo lesions typically appears in a punctate, perifollicular pattern, and areas of vitiligo lesions containing no hair or white hairs—where autoimmunity has not spared the follicular melanocyte populations—do not repigment. Annual Review of Immunology “Vitiligo: Mechanisms of Pathogenesis and Treatment” Michael L. Frisoli, Kingsley Essien, and John E. Harris)
Treatment: Both topical and systemic treatments that block IFN-γ signaling can effectively reverse vitiligo in humans; however, disease relapse is common after stopping treatments. Autoreactive resident memory T cells are responsible for relapse, and new treatment strategies focus on eliminating these cells to promote long-lasting benefit.