The two layers of the skin consist of the epidermis and dermis. The epidermis is the uppermost part of the skin, which we can see all over our bodies. The epidermis and dermis are composed of their own layers, which we will discuss in a bit. Below the dermis is the hypodermis, which consists of adipose tissue. Below the hypodermis is the subcutaneous layer, which is the location site for many of our injectable drugs, such as insulin. Between the layers there are many hair follicles, which make up the pilosebaceous unit, consisting of hair, sebaceous gland, apocrine and eccrine sweat glands, and the arrector pili muscle. The pilosebaceous unit is particularly important in thermoregulation and electrolyte homeostasis - sweat glands function to release NaCl and H2O from the body, producing a cooling effect and maintaining electrolyte balance.
Before we get into the functions of the skin, I will go back and summarize the various layers in the epidermis and dermis. The epidermis is composed of 5 or 6 layers, depending on the type of skin. These layers include (from bottom up): Stratum basale, spinosum, granulosum, lucidem (only on thick skin - soles of feet, palms of hands), and the stratum corneum. These sit on the basement membrane, which connects the dermis to the epidermis. The stratum basale consists of merkel cells and cuboidal cells. The stratum spinosum contains melanocytes, responsible for color of the skin, and langerhans cells, which are antigen-presenting cells involved in the immune response. The stratum corneum, the uppermost layer, is also the thickest layer of the skin.
The dermis is made up of many types of cells: fibroblasts, which make up the extracellular matrix, including collagen, mast cells, sensory nerve fibers, and capillaries. The dermis is the area of the skin containing the nerves and blood supply for the skin. Different sensations which are felt on the skin are pressure, pain, and temperature.
The functions of the skin are as follows: 1)protection/barrier for the underlying tissues, 2)wound healing, 3)vitamin D synthesis, 4)sensation, 5)thermoregulation, and 6)secretion. The skin acts as a barrier for bacteria (by secreting its own antimicrobials), UV light, and injury. The skin is extremely efficient at wound healing, as evidenced by the quick healing of superficial cuts and scrapes. Vitamin D synthesis occurs when the sun causes the conversion of 7-dehydrocholesterol to cholecalciferol and eventually into active vitamin d, which is crucial in the regulation of calcium. The skin also detects sensations, as mentioned above, pain, temperature, and pressure. The skin also secretes sweat, antimicrobials, and sebum. Sweat helps to regulate temperature, antimicrobials help to prevent bacterial infection on the skin, and sebum acts as a lubricant and fat secretor.
Pharmacologically, the skin conditions which are included in NAPLEX prep are: acne, cold sores, dandruff, alopecia, eczema, hyperhidrosis, fungal infections, diaper rash, hemorrhoids, pinworm, lice/scabies, minor wounds, burns, poison ivy/oak/sumac, inflammation/rash, and sunscreens. I will be delving deeper into these subjects individually throughout the duration of this APPE rotation. Please refer to this GoogleDoc Folder for all NAPLEX review of skin:
Pharmacotherapy Summary for all NAPLEX Skin Conditions
There are little data on the prevalence of dermatological disorders in various populations. Estimates and extrapolation of survey results reveal that anywhere from 12% to 31% of visits to physicians involve dermatological problems, depending on location, age, ethnicity, and type of medical provider. Pharmacists are routinely asked for assistance with the diagnosis and treatment of many common skin conditions. Therefore, it is important for pharmacists to recognize common skin disorders, so they can make appropriate recommendations about self-care and referral.
1) RxPrep NAPLEX Review 2021. Chapter 39: Common Skin Conditions. Page 566-581
2) Common Skin Disorders. In: Herrier RN, Apgar DA, Boyce RW, Foster SL. eds.Patient Assessment in Pharmacy. McGraw Hill; 2015. Accessed April 05, 2022. https://accesspharmacy.mhmedical.com/content.aspx?bookid=1074§ionid=62364288
Fungal Infections: Toenail & Fingernail
Onychomycosis, a fungal infection of the nail, is often caused by tinea unguium. Onychomycosis can cause pain, discomfort, and disfigurement, and can lead to physical limitations (difficulty walking, standing, etc.) Discoloration and disfigurement can lead to self-esteem and psychological issues as well - this is a common theme throughout our coverage of skin conditions. Onychomycosis is treated with monotherapy of topical drugs in mild cases and for patients who can not tolerate systemic therapy. Otherwise, topical drugs are used in combination with systemic treatments or alone as prophylaxis. Topical drugs alone are NOT potent enough to cure most infections.
Itraconazole and terbinafine are approved for this use and most commonly used; fluconazole and posaconazole are used off-label. Griseofulvin is rarely ever used in treatment of fungal nail infections. Pulse therapy (intermittent) can be used to reduce costs and possibly toxicity, but may not be as effective. A 20% KOH smear is essential for diagnosis, as other conditions can produce similar presentations.
1) RxPrep NAPLEX Review 2021. Chapter 39: Common Skin Conditions. Page 573.
Fungal Infections: Skin
Athlete’s foot, also known as tinea pedis, is a fungal infection of the foot caused by various fungi, commonly trichophyton rubrum. Symptoms of tinea pedis include feet itching, peeling, redness, mild burning, and sometimes sores. This is a common infection, particularly among those using public pools, showers, and locker rooms. For these reasons, suggesting shoes in these situations may help prevent recurrent infections. Diagnosis of tinea pedis is usually symptom-based, but if the underlying cause of infection is unclear, the skin can be scraped off and viewed under a microscope. Other conditions which may cause redness and itching of the feet are psoriasis or eczema. Treatment of tinea pedis is topical antifungal medications, except in severe cases.
**** itch, or tinea cruris, is a fungal infection affecting the ********, inner thighs, and buttocks. The rash appears red, is itchy, and can be ring-shaped. **** itch is not very contagious, but can be spread person-to-person with close contact. Important counseling points for tinea cruris include keeping the area dry by using a clean towel after showering. Antifungal cream preparations tend to work best for **** itch.
Ringworm, or tinea corporis, is not a worm, but a skin fungal infection. Ringworm can appear anywhere on the body and typically looks like circular, red, flat sores (one or more, may overlap) usually with dry, scaly skin. Occasionally the ring-like presentation is not present - just itchy, red skin. The outer part of the sore can be raised while the skin in the middle of the lesion appears normal. Ringworm can spread from person to person or by contact with infected animals. Most cases are treated topically. Tinea capitis is ringworm on the scalp - it affects mostly young children in crowded, low income situations. Tinea capitis requires systemic antifungal therapy, with the same drugs used for onychomycosis.
Topical Cutaneous candida infections cause red, itchy rashes, most commonly in the groin, armpits, or anywhere the skin folds. These are more likely in obese persons because they tend to have more folds in the skin. The infection can be present in unusual places such as under the *******, if the skin is moist. Diabetes is also a known risk factor for developing cutaneous candida infections. Occasionally, fungal infections appear in the corner of the nails (on the skin, not in the nail bed). If this is a suspected bacterial infection, OTC antibiotic topicals or mupirocin can be used. Candida can also cause diaper rash in infants.
1) RxPrep NAPLEX Review 2021. Chapter 39: Common Skin Conditions. Page 572.
Hyperhidrosis: NAPLEX Review
Hyperhidrosis, or excessive sweating, is a common skin condition which is associated with increased social stress and comorbid psychological issues. Diagnosis of hyperhidrosis is based on physical exam and thorough medical history. Treatment of hyperhidrosis depends on the severity of sweating as well as the location of sweating (underarms, hands, feet, etc). RxPrep discusses hyperhidrosis very briefly, so in addition to this review, I will be posting a more in-depth look into the psychosocial implications of hyperhidrosis and the effect it may have on a patient’s quality of life. Current FDA-approved treatments for hyperhidrosis include Qbrexa (glycopyrronium), a product available in single-use cloth wipes to limit sweating under the arms. Botox injections are also an FDA-approved treatment for hyperhidrosis of the underarms.
1) RxPrep NAPLEX Review 2021. Chapter 39: Common Skin Conditions. Page 571.
Eczema (Atopic Dermatitis): NAPLEX Review
“Eczema” or atopic dermatitis, is a general term for many types of skin inflammation. Eczema is most commonly seen in children and infants, but it can occur at any age. Eczema presents dermatologically as a skin rash, which becomes crusty and scaly. The rash is red, itchy, dry, and sore - blisters may or may not develop. Common affected areas include the elbows, behind the knees/ears, face (often on the cheeks), buttocks, hands, and feet. It is important to note that certain products or environmental conditions can trigger eczema, such as allergens (in soaps, perfumes, etc), environmental irritants (pollen), stress, or changes in the weather.
Hydration is essential to reduce severity of atopic dermatitis - patients should be advised to use unscented moisturizers such as CeraVe or Eucerin, and to maintain adequate humidity in the home (which can be particularly difficult in the winter months). If necessary, pharmacological treatments can include topical steroids, short courses of oral steroids, antihistamines for itching, and finally immunosuppressant calcineurin inhibitors (if topical steroids with hydration are not adequate). In severe, refractory cases of atopic dermatitis, oral immunosuppressants such as cyclosporine and MTX, or monoclonal antibody drugs can be used. Dupilumab (Dupixent) is an FDA-approved monoclonal antibody for the treatment of moderate to severe eczema. Dupixent is administered as a biweekly subcutaneous injection; however, there are other drugs used for eczema off-label.
1) RxPrep NAPLEX Review 2021. Chapter 39: Common Skin Conditions. Page 571.
Alopecia: NAPLEX Review
Alopecia, or hair loss, is something that commonly happens as people age, but also can occur due to hormonal factors, medical conditions, and medications. The most common cause of hair loss is hereditary male-pattern baldness, and less common is female-pattern baldness. Hormonal changes in women that can result in hair loss are usually associated with pregnancy, childbirth, or menopause (during pregnancy, “baby hairs” tend to break at the forehead, and during menopause hair tends to thin). Medical conditions that can cause hair loss include hypothyroidism, alopecia areata (an autoimmune disorder - which I will be covering later on), scalp infections, and some other conditions such as lupus. Drugs that can cause alopecia include various chemotherapeutic agents (hair cells rapidly divide and are greatly affected by chemotherapy), valproate, spironolactone, heparin, warfarin, clomiphene, hydroxychloroquine, interferons, lithium, some times of oral contraceptives (levonorgestrel), and procainamide. Disorders such as zinc deficiency or vitamin D deficiency can also contribute to hair loss. Medications that treat alopecia work modestly - many people will end up seeking surgical intervention, such as hair transplants and others. Hair loss can be a regular part of the aging process, but when alopecia affects younger individuals, it often can impact their self confidence and quality of life. One major issue with all the therapeutic options we have for alopecia is that none of them are a permanent solution - all medications for alopecia must be used consistently to maintain hair growth.
1) RxPrep NAPLEX Review 2021. Chapter 39: Common Skin Conditions. Page 570.
Pathophysiology and Pharmacotherapy of Dandruff
Seborrheic dermatitis is a common, chronic, relapsing form of eczema affecting sebaceous glands present on the scalp. Seborrheic dermatitis can be either inflammatory or noninflammatory - non inflammatory seborrheic dermatitis is the condition commonly referred to as “dandruff”. Dandruff affects children and adults alike, but the prevalence is greatest in young adults and in older people. Dandruff is more common among males vs. females. Infantile seborrheic dermatitis affects babies under the age of 3 months old, and is usually self-limiting, resolving by 6-12 months old. Dandruff presents as bran-like scaly patches scattered within hair-bearing areas of the scalp. Along with itchiness and discomfort, patients may also experience psychosocial effects of dandruff, particularly in young adulthood.
The cause of dandruff is not entirely understood, but the most acceptable culprit is an overgrowth of various species of Malassezia, a commensal, non-pathogenic yeast found on the skin. The issue with proliferation of Malassezia is that its metabolites, such as oleic acid and indole-3-carbaldehyde, may cause an inflammatory reaction. Presentation and likelihood of dandruff may differ by person due to differences in skin barrier lipid content. Some risk factors that contribute to development of dandruff are oily skin (a.k.a seborrhea), family history of dandruff or psoriasis, immunosuppression due to drugs or diseases, neurological and psychiatric diseases (Parkinson’s, TD, epilepsy, spinal cord injury, Down’s Syndrome), treatment for psoriasis with psoralen and PUVA therapy, as well as increased stress or lack of sleep.
Adults with dandruff present with affected areas on the scalp, face, and/or upper trunk. Typical features include winter flare-ups, minimal itching, combination oily and dry mid-****** skin, diffuse scale in the scalp, blepharitis, salmon-colored scaly patches in skin folds on both sides of the face, rash in the armpits, under the *******, in groin folds, and genital creases, as well as superficial folliculitis on the cheeks and upper trunk.
There are several options for the treatment of dandruff in adult patients. A store-bought, inexpensive dandruff shampoo can be tried first, and if ineffective, ketoconazole antifungal shampoo can be used. Some of the OTC options include Selsun Blue (active ingredient: selenium sulfide) and Head and Shoulders (active ingredient: zinc pyrithione). Nizoral A-D is an OTC option containing 1% ketoconazole, whereas the prescription strength ketoconazole cream/gel/foam is 2%. Other treatment options include topical steroids to reduce itching - should be applied daily for a few days every so often. Calcineurin inhibitors such as tacrolimus can be used as steroid alternatives. Coal tar cream can be applied to scaling areas and removed several hours later by shampooing. Combination therapy is often advisable - one product alone may not be sufficient for controlling moderate-severe dandruff.
Oakley A. Seborrhoeic dermatitis. DermNetNZ. https://dermnetnz.org/topics/seborrhoeic-dermatitis/. Published 1997. Latest update by Dr Jannet Gomez, October 2017.
RxPrep NAPLEX Review 2021. Chapter 39: Common Skin Conditions. Page 569.
Drug-Induced Skin Reactions
The various types of drug-induced skin reactions can be classified as follows: erythematous reactions, angioedema/anaphylaxis, fixed drug eruptions, drug hypersensitivity syndrome, erythema nodosum, Steven-Johnson Syndrome (SJS), Toxic epidermal necrolysis syndrome (TENS), drug induced pigmentation/photosensitivity, and acneiform eruptions. The following will summarize these reactions (with photos), and describe in greater depth the causative agents and clinical presentations of each.
1. Erythematous Reactions
Clinical Presentation: These reactions are the most common ADRs involving the skin. This eruption is considered a type IV delayed cell-mediated hypersensitivity reaction. The eruption typically occurs 4 to 14 days after the causative drug is initiated; however, the reaction may occur 1 to 2 days after discontinuation of the drug. Upon a second exposure, the eruption may occur more rapidly. Lesions are symmetric erythematous macules or papules, which may be pruritic and usually develop on the trunk or upper extremities before progressing. Patients may experience a low-grade fever.
Causative Agents: penicillins, cephalosporins, sulfonamides, anticonvulsants, and allopurinol
Treatment: Primary treatment involves discontinuing the causative agent; however, if the drug is required for essential therapy, consideration may be given to continuation of the agent unless symptoms associated with the eruption suggest a more serious reaction. Topical corticosteroids, systemic corticosteroids, or antipruritic agents may also be considered. The eruption generally resolves within 7 to 14 days after the causative agent is discontinued.
2. Anaphylaxis: Angioedema, Urticaria
Clinical Presentation: Urticaria (hives) is a common, acute, transient reaction sometimes referred to as the cutaneous expression of anaphylaxis. It is characterized by pruritic monomorphic erythematous and edematous papules and plaques. The onset of symptoms is rapid, sometimes within minutes, and the papules and plaques last from a few hours to 24 hours. New lesions, however, may continually develop. In contrast, angioedema is defined by involvement of dermal and subcutaneous tissues and is described as pale or pink swelling that affects the face, buccal mucosa, tongue, larynx, and pharynx. Anaphylaxis may complicate urticaria and angioedema and may involve additional body systems, leading to shock and death. Urticaria, angioedema, and anaphylaxis are a consequence of either an immunoglobulin E (IgE)–mediated type 1 hypersensitivity reaction or an anaphylactoid mechanism involving histamine or other inflammatory mediators.
Causative Agents: ACEIs (within the first several months to 3 years) are notorious for causing angioedema. Examples of anaphylactoid reactions include responses to radiocontrast media, opiate-induced urticaria, and vancomycin-induced red man syndrome
Treatment: Management of this reaction consists of discontinuing the causative agent. Histamine receptor (H1) blockers, systemic corticosteroids, and epinephrine may also be required acutely.
3. Fixed Drug Eruption
Clinical Presentation: These eruptions present as pruritic, red, raised lesions that may blister or develop into plaques. A burning or stinging sensation may also be noted. Lesions typically develop in minutes to days of drug initiation and typically resolve within days; however, hyperpigmentation may remain for months. The lesions may develop anywhere on the body and may include the mucous membranes. When the causative agent is readministered, the lesions recur in the same area as the primary eruption.
Causative Agents: Any drug can cause a fixed drug eruption, but most notably seen with antimicrobial agents (tetracyclines, sulfonamides, metronidazole, nystatin), anti-inflammatory drugs (salicylates, NSAIDs), barbiturates, and oral contraceptives.
Treatment: typically resolves within days of d/c the causative drug
4. Erythema Nodosum Eruption
Clinical Presentation: A delayed-type hypersensitivity reaction that most often presents as erythematous, tender nodules on the shins and knees. These lesions are irregularly shaped and painful when palpated. Erythema Nodosum Eruptions are most common in women between 20-40 years old.
Causative Agents: oral contraceptives, sulfonamides, analgesics/NSAIDS, potassium iodide, phenytoin.
Treatment: usually self-limiting and resolves slowly over several weeks after d/c the offending agent.
5. Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis Syndrome (TENS)
Clinical Presentation: SJS and TENS are marked by large, painful blisters. They can also cause large areas of the top layer of your skin to come off, leaving raw, open sores. SJS involves less than 10 percent of the body, while TENS involves more than 30% of the body surface area. Symptoms are very acute, and begin within 4 weeks of drug exposure. Symptoms have also been documented to occur days after drug withdrawal. The eruption occurs even more rapidly when the causative agent is rechallenged. Initial symptoms include a prodromal phase of fever, sore throat, and stinging eyes. The skin blisters and mucous erosions occur 1 to 2 days later, with extensive epidermal detachment and sloughing. The rash may cover the entire body. Initially, the lesions are irregularly shaped, erythematous, purpuric macules that progressively coalesce. Necrotic epidermis detachment occurs. The mucous membranes (buccal, ocular, nasal, and genital) are affected in at least 85% of patients. Additionally, epithelium of the gastrointestinal and respiratory tracts may be involved. Patients may also have increased hepatic enzymes and leukopenia; however, the syndromes are not typically associated with eosinophilia. A marked loss of fluids, a drop in blood pressure, electrolyte disturbances, and infection may occur. SJS is fatal in 5% to 10% of patients and TEN is fatal in >30% of patients.
Causative Agents: long-acting sulfonamides, allopurinol, carbamazepine, fluoroquinolones, hydantoin, phenylbutazone, piroxicam, and others.
Treatments: Discontinuation of the causative agent is vital. Treatment is symptomatic and supportive. No other treatments are universally accepted, as the use of corticosteroids and other therapies is controversial.
6. Drug-Induced Hyperpigmentation/Photosensitivity
Clinical Presentation: Photosensitivity reactions may manifest as either a photo-allergic or phototoxic reaction. Some drugs are capable of producing both types of reactions. Phototoxic reactions are common and often predictable. Drugs that induce a phototoxic reaction absorb ultraviolet A (UVA) light. Phototoxicity is characterized by the rapid onset of a burning sensation. Clinically, patients present with an exaggerated sunburn, followed by hyperpigmentation. This reaction occurs only on sun-exposed skin. Less common clinical forms of the reaction are photo-onycholysis (phototoxicity involving the nails) and pseudoporphyria (a bullous photosensitivity disorder). Photoallergy is less common than phototoxicity and is a result of cell-mediated hypersensitivity. Photoallergy occurs from UVA transformation of drugs into allergens. This reaction may involve exposed skin and skin that is not exposed to the sun. Unlike the more immediate phototoxic reaction, photoallergy may not present until 24 to 72 hours post sun exposure. A photoallergy clinically appears as an acute, subacute, or chronic dermatitis.
Causative Agents: antibiotics (tetracyclines, fluoroquinolones, sulfonamides), TCAs, hydrochlorothiazide, beta blockers, amiodarone, sulfonylureas, sunscreens containing PABA, oral contraceptives, phenothiazine antipsychotics, and photosensitizing agents.
Treatment: Reduce the dose of the suspected agent. If dose reduction is not effective, recommend systemic corticosteroids or topical antihistamines. For a photoallergic reaction, administer antihistamine + corticosteroids. Topical corticosteroids and/or oral NSAIDs can also be used for pain and inflammation. Use of cold compresses also can provide pain relief to affected areas.
Clinard V, Smith J. Drug-Induced Skin Disorders. US Pharmacist. https://www.uspharmacist.com/article/drug-induced-skin-disorders. Published 04/23/2012.
Moyer N. How to Identify and Treat a Drug Rash. Healthline. https://www.healthline.com/health/drug-rash. Published 02/12/2019.
Treatment of Acne
There are a variety of elements that contribute to the formation of acne, including bacterial presence, sebum, diet, and age. Androgens are the male sex hormones, and the primary determinant of acne development, especially in pubescent teens. Formerly known as P. acnes, the bacteria known to cause acne has been renamed as Cutibacterium acnes. Diets high in glycemic index (sugars, carbohydrates) and dairy products (milk, cheese, etc.) can worsen acneiform eruptions. The presence of acne-causing bacteria in combination with excess sebum, secreted from sebaceous glands in the skin, lead to pore clogging and development of acne lesions, which are classified in terms of lesion type and severity.
The various types of acne lesions include white heads (closed comedones), blackheads (open comedones), small bumps, and most severely inflamed and often painful cysts and nodules. Severity of acne is classified as mild (a few, occasional pimples), moderate (presence of inflammatory papules), and severe (presence of nodules and cysts). Acne is also classified as being inflammatory vs. non-inflammatory. The above photo illustrates the different types of acne and their classifications. Treatment of acne is based on these classifications - type of acne lesions present and the number of lesions present. It is important to note that much of the acne which brings patients to seek treatment is on the face, but acne can exist all over the body, including the chest and back.