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Self-Treatment of Acne, Dermatitis, and General Skin Care

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1 Self-Treatment of Acne, Dermatitis, and General Skin Care
John Pedey-Braswell 2005 Pharm.D. Candidate University of Washington School of Pharmacy Pharmacy 301 June 4, 2003

2 Lecture Overview Skin Anatomy and Physiology Acne
Dermatitis and Dry Skin

3 Skin Facts Largest Organ in the Body.
Variable Thickness, averages about 1-2mm. Skin, Hair, and Nails serve as protective barrier between body and environment. Success of protection depends on age, immunologic status, underlying disease states, use of certain medications, and preservation of intact stratum corneum (outermost dead layer).

4 The Skin Three Layers epidermis dermis hypodermis Glands sebaceous

5 Hypodermis Also known as subcutaneous tissue, is the innermost area of skin. Consists of loose connective tissue and adipose firmly anchored to the dermis above it. Varying thickness allows necessary pliability of human skin. Fatty component facilitates thermal control, holds food reserve, and provides cushioning or padding.

6 The Skin Three Layers epidermis dermis hypodermis Glands sebaceous

7 Dermis Approximately 40 times thicker than the epidermis above.
Consists of elastic and connective tissue (collagen and elastin) surrounded by a mucopolysaccharide substance. Fibroblasts, mast cells, nerves, blood supply. Sensation of itching arises in upper portion, stinging in middle region, pain in the lowest level.

8 The Skin Three Layers epidermis dermis hypodermis Glands sebaceous

9 Epidermis Outermost layer consisting of compact, avascular stratified epitheal cells Five distinct layers (from bottom to top): strata germinativum, spinosum, granulosum, lucidum, corneum. Keratinocytes in the stratum germinativum divide and move upwards to the skin surface. In the process, they change from living cells to dead, thick-walled, flat, nonnucleated cells that contain keratin (a fibrous, insoluble protein). Melanin is produced in stratum spinosum.

10 Stratum Corneum Composed of flat, scaly, dead (keratinized) tissue.
Outermost cells are flat plates that are constantly shed (desquamated) and replaced by new cells continually generated by mitotic processes in the basal cell layer. Complete cycle from basal cell formation to shedding is 28 to 45 days. Flexibility of this layer depends on its water content, which is normally 10-20% by weight. Influenced by humidity, temperature, surfactants, and trauma. Keratin can absorb many times its weight in water, and thus retains water to maintain the skin’s flexibility and integrity. When the skin’s water content drops below 10%, chapping occurs and the stratum corneum becomes brittle and cracks easily – allowing irritants and bacteria to penetrate more easily, leading to inflammation and possibly infection.

11 Acne vulgaris (common acne)
Most common adolescent skin disorder, often linked to the onset of puberty. Approximately 85% of all people between ages years will develop it to some degree. Onset in males is typically between years. Usually clears by the mid-20s. Female onset is usually years. Unfortunately, may persist into 30s or 40s, and worsen in menopause. First lesions may precede other signs of puberty and diagnosed as early as age 7 years. Papular lesions generally appear during the mid-teen years, while nodular lesions appear in the late teens.

12 Dermal Pilosebaceous Units
Acne vulgaris has its origin in these units. Consist of a hair follicle and associated sebaceous glands. Connected to the skin surface by the infundibulum – an epithelial tissue lined duct through which the hair shaft passes. Sebaceous glands produce sebum, which passes to skin surface through infundibulum then spreads over the skin to retard water loss and maintain hydration of skin and hair. Glands are more common on the face, back, and chest – and so is acne.

13 Typical Distribution of Pilosebaceous Units

14 Origins of Acne Vulgaris
Production of androgenic hormones increases as a male or female approaches puberty. Precise cause of acne is not known, but believed to be linked to this increase and closely related to acne development. Androgenic hormones stimulate the sebaceous glands – appearance of acne usually noticed at actual onset of puberty. Four processes linked to increase in androgens are closely related to acne development: 1. Abnormal keratinization of cells in the infundibulum; 2. Increase in sebum production; 3. Accelerated growth in Propionibacterium acnes; 4. Occurrence of inflammation.


16 A Zit is Born Abnormal keratinization of cells in the infundibulum leads to increased cohesiveness between the cells, and results in obstruction of the follicle rather than the removal of these cells to the skin surface. The trapped, keratinized cells plug and distend the follicle to form a microcomedo, the initial lesion of acne. As more cells and sebum accumulate, microcomedo enlarges and becomes visible as a closed comedo or whitehead. This is the precursor to other developing acne lesions. Hair in follicle can determine extent of comedo formation. Thin and small hairs can become trapped in the plug, while thick, heavier hairs (like on the scalp or in the beard) will push the plug to the surface, thus preventing comedo formation.

17 More on Zit Formation Open comedones, or blackheads, occur when sufficient material accumulates behind the plug, and the orifice of the follicular canal becomes distended, allowing the plug to protrude. The tip of the plug of the open comedo may darken because of melanin content. Increase in circulating androgens stimulates the production of sebum, which is prevented from reaching the surface of the skin by the obstructing keratinized cells. At the same time the bacteria P.acnes undergoes accelerated growth. P.acnes is a major contributor to inflammatory acne lesions due to lipase production and breakdown of sebum to free fatty acids. Colony counts are higher in patients with acne than in those without it. Resulting inflammation causes localized tissue distruction.

18 Inflammatory Acne Begins with closed comedones that distend the follicle, causing the cellular lining of the walls to spread and become thin. Primary inflammation of the follicle wall develops with the disruption of the epitheleal lining and lymphocyte infiltration. Severe inflammatory reaction follows if the follicle wall ruptures spontaneously or is ruptured by picking, squeezing, attempted extraction by dermatologist, or if contents are discharged into the surrounding tissue. May result in abscesses, which can cause scars or pits after healing. Pustules or purulent nodules are more likely to cause permanent scarring.

19 A Picture is Worth a Thousand Words
FIGURE 1. Stages of acne. (A) Normal follicle; (B) open comedo (blackhead); (C) closed comedo (whitehead); (D) papule; (E) pustule. Source: American Academy of Family Physicians.

20 Closed Comedones (Whiteheads)
(L) (R):

21 Open Comedones (Blackheads)
(L) (R)

22 Inflammatory Acne: Papules
A papule is defined as a small (5 millimeters or less), solid lesion slightly elevated above the surface of the skin. A group of very small papules and microcomedones may be almost invisible but have a "sandpaper" feel to the touch. A papule is caused by localized cellular reaction to the process of acne. This photo shows papules and comedones on the face of an acne patient.

23 Inflammatory Acne: Pustules
A dome-shaped, fragile lesion containing pus that typically consists of a mixture of white blood cells, dead skin cells, and bacteria. A pustule that forms over a sebaceous follicle usually has a hair in the center. Acne pustules that heal without progressing to cystic form usually leave no scars. This photo shows pustules, papules and comedones on the face of an acne patient. Source:

24 Inflammatory Acne: Macules
A macule is the temporary red spot left by a healed acne lesion. It is flat, usually red or red-pink, with a well defined border. A macule may persist for days to weeks before disappearing. When a number of macules are present at one time they can contribute to the "inflamed face" appearance of acne. This photo shows the "red face" appearance of acne with macules. Source:

25 Inflammatory Acne: Nodulocystic
Like a papule, a nodule is a solid, dome-shaped or irregularly-shaped lesion. Unlike a papule, a nodule is characterized by inflammation, extends into deeper layers of the skin and may cause tissue destruction that results in scarring. A nodule may be very painful. Nodular acne is a severe form of acne that may not respond to therapies other than isotretinoin. A cyst is a sac-like lesion containing liquid or semi-liquid material consisting of white blood cells, dead cells, and bacteria. It is larger than a pustule, may be severely inflamed, extends into deeper layers of the skin, may be very painful, and can result in scarring. Cysts and nodules often occur together in a severe form of acne called nodulocystic. Systemic therapy with isotretinoin is sometimes the only effective treatment for nodulocystic acne. Source:

26 What About Rosacea? Referred to as "adult acne," rosacea causes facial swelling and redness and therefore, is easy to confuse with other skin conditions, such as acne or sunburn. Those who have rosacea might first notice a tendency to flush or blush easily. The condition can occur over a long period of time and often progresses to a persistent redness, pimples and visible blood vessels in the center of the face that might eventually involve the cheeks, forehead, chin and nose. Other areas that can be affected by rosacea are the neck, ears, chest and back. Sometimes, rosacea affects the eyes. The pimples of rosacea, which often occur as the disease has progressed, are different than those of acne because blackheads and whiteheads rarely appear. Rather, people who have rosacea have visible small blood vessels and their pimples—some containing pus—appear as small, red bumps. Rosacea can be controlled with medications and lifestyle changes. Early intervention by a dermatologist, the expert in skin, hair and nail conditions, is key to successful treatment. Delay in diagnosis and treatment because of non-physician treatments can result in scarring.

27 Things Proven to Make Acne Worse
Heredity – chances of offspring developing acne are higher when both parents have had acne than when only one parent has the disorder. Skin Hydration – decreases the size of the pilosebaceous duct orifice. Acne can be worsened by high humidity environments and tight-fitting clothing. Local irritation (acne mechanica) – occlusive clothing, headbands, helmets, chin straps can aggravate acne. Exposure to dirt, vaporized cooking oils, industrial chemicals may cause occupational acne. Acne cosmetica is a mild form of acne on the face, cheek, and chin. Typically closed, noninflammatory comedones. Oil-based cosmetics, including shampoos, may be occlusive and plug the follicles, exacerbating or even initiating acne.

28 Unsubstantiated Factors
Chocolate Nuts Fats Colas Carbohydrates Sexual Activity – acne begins at puberty and sexual activity may begin at the same time, but not a cause and effect relationship.

29 Treatment Approaches Goals are to unblock pilosebaceous ducts and keep orifices open, plus avoiding factors that worsen acne. Talk with your pharmacist. Some medications such as corticosteroids (prednisone, et al) can cause acne. She, or he, can help with self-care product selection and provide feedback. Self-treatment is appropriate for mild-to-moderate noninflammatory acne (open or closed comedones). Do NOT add nonprescription medications to prescribed regimens unless recommended by prescriber.

30 Proper Skin Cleansing Removing excess sebum from the skin in a program of daily washing produces a mild drying of the skin and, perhaps, mild erythema. Affected areas should be washed at least twice daily (more frequently if skin is oily) with warm water, medicated or unmedicated soap, and a soft washcloth; then patted dry. Washing should not be excessively vigorous; it should cause barely noticeable peeling that can loosen comedones Washing intensity and frequency should be reduced and a less drying soap considered if tautness occurs. Facial soaps that do not contain moisturizing oils are usually satisfactory. A certain degree of drying action is desirable, so facial soap should be tried before surfactant soap substitutes. Antibacterial soaps have no clinical value. Salicylic acid, sulfur, and resorcinol are safe and effective for treating acne, but their effectiveness as soaps is questionable because little, if any, residue is left on the skin after washing. Abrasive agents may be useful in treating noninflammatory acne, but avoid in inflammatory acne because of increased irritation. If inconvenient to wash during the day, cleansing pads can be used at school or work.

31 Benzoyl Peroxide Available in diverse dosage forms such as lotions, gels, creams, cleansers, masks, and soaps. Different formulations are not equivalent – the drying effect of the gel base is superior to a lotion or cream of the same strength (most gels are Rx only). Washes and cleansers are widely used as treatment adjuncts, but have little or no comedolytic effect. Causes irritation and desquamation that prevents closure of the pilosebaceous orifice. Irritant effect causes an increased turnover rate of epithelial cells lining the follicular duct, which increases sloughing and promotes resolution of the comedones. May take 4-6 weeks see full effect. Its oxidizing potential may contribute to antibacterial activity against P.acnes. AEs: excessive dryness, peeling, skin sloughing, edema indicate that lower concentrations should be used for shorter periods of time. Can cause transient stinging or burning. May bleach hair or clothing. Avoid excessive exposure to sun or tanning beds – may enhance the ability of UV rays to produce skin cancer.

32 Salicylic Acid/Sulfur/Resorcinol
Salicylic acid is a mild comedolytic agent, available in nonprescription acne products. Acts as surface keratolytic, and enhances absorption of other agents. Considered adjunctive therapy, but cleansing pads are safe, effective, and superior to benzoyl peroxide in preventing and clearing both comedones and inflammatory lesions of acne. Precipitated, or colloidal, sulfur is in products as a keratolytic agent. Effective agent for resolving existing comedones, but continued use may have comedogenic effect. Noticeable odor and color makes sulfur products a tough sell for consumers. Resorcinol not recognized as safe and effective by the FDA, unless in combination with sulfur – probably enhances keratolytic effect.

33 Prescription Remedies: Antibiotics
Used to control growth of bacteria Propionibacterium acnes in pilosebaceous ducts. Comedonal acne can usually be controlled with topical antibiotics such as clindamycin or erythromycin. Inflammatory acne often needs systemic antibiotic therapy with a tetracycline (tetracycline, doxycycline, or minocycline), erythromycin, or rarely ampicillin.

34 Prescription Remedies: Hormonal
Oral contraceptives may be useful adjunctive therapy for all types of acne in females. Sebum production is controlled by androgens, and oral contraceptives are known to reduce androgen levels by increasing sex hormone binding globulin levels – reduces the availability of biologically active free androgens. Pills containing norgestimate or desogestrel (Ortho Tri-Cyclen, Ortho Cyclen, Desogen) appear to work best. Two to four monthes therapy may be required before improvement is seen, and relapses are common if medication is discontinued. The diuretic spironolactone is also used to control androgen levels.

35 Prescription Remedies: Tretinoin
Tretinoin (Retin-A®): all-trans-retinoic acid. Used primarily in topical treatment of acne vulgaris when comedones, papules, and pustules predominate. Appears to stimulate mitosis and turnover of follicular epithelial cells and reduce their cohesiveness, facilitating extrusion of existing comedones and preventing formation of new ones. May take 6-8 weeks to see noticeable results. Skin irritant: may cause transitory stinging and feeling of warmth. Normal use produces some erythema and peeling similar to that of a mild sunburn. Avoid contact with mucous membranes and eyes. Some patients will experience edema, blistering, and crusting of the skin. Photosensitivity may occur, as well as temporary hypo- or hyperpigmentation. Contraindicated in pregnancy, some case reports of congenital abnormalities. See isotretinoin.

36 Prescription Remedies: tazorotene and adapalene
Tazarotene (Tazorac®): prodrug that is de-esterified in the skin to release active drug tazorotenic acid (a retinoid). Same action, AEs, contraindications as tretinoin. Available as 0.1% gel or cream. Adapalene (Differin®): retinoid analog, a naphthoic acid derivative. Same action, AEs as tretinoin, HOWEVER no evidence that it is harmful to fetus. Available as 0.1% cream, solution, or gel.

37 Prescription Remedies: isotretinoin
Isotretinoin (Accutane®): 13-cis-retinoic acid. Generic version now available. 10mg, 20mg, 40mg capsules. Used in severe inflammatory acne after all other methods exhausted. Also used to treat some cancers. Probably works on similar transcription pathways as tretinoin. Dose-related reduction in sebum excretion, and subsequent decrease in P.acnes growth. Dosed by patient weight 0.5-2mg/kg. AEs: dryness of mucous membranes and skin, with scaling, fragility, and erythema. Hair thinning. Increases serum triglycerides. Muscle and joint pain. Visual disturbances. Psychosis? Known teratogen and abortifacient. Prescribers must counsel patients of risks before prescribing. Females need negative pregnancy test, contraceptives starting one month prior to start of isotretinoin, and taken for one month after terminating drug. Prescriptions must have special sticker to be filled by pharmacist.

38 Retinoid-Induced Teratogenicity

39 Retinoids Work by Initiating DNA Transcription

40 Funny, He Doesn’t Look Like a Nazi
Dr. Albert Kligman, University of Pennsylvania, Professor emeritus -- the father of retinoid-based acne treatments. Conducted experiments on prisoners at Holmesburg Prison (Phildelphia) between mid-50s to 1974. “All I saw before me were acres of skin.”

41 Percutaneous Absorption of Drugs
Drug must be released from its vehicle if it is to exert and effect at the desired site of activity. Release of drug occurs at interface between skin surface and applied layer of product. Many physical-chemical factors determine relationship between the rate of absorption and the amount of drug released. The degree of skin hydration and thickness of applied layer of drug are also important. Increased temperature at skin surface increases blood flow to the area, and enhances rate of percutaneous absorption.

42 Percutaneous Absorption of Drugs
Oily bases such as petrolatum are transiently occlusive, promote hydration of the skin and generally increase molecular transport of drug. (ointments) Hydrous emulsions are less occlusive. Water-soluble bases (PEGs) are minimally occlusive, and may attract water from the stratum corneum and decrease drug transport. (solutions, gels, some creams) Powders with hydrophilic ingredients presumably decrease skin hydration because they promote evaporation from skin by absorbing available water. Stratum corneum provides the greatest resistance to drug absorption and is thought of as the rate-limiting step in percutaneous drug delivery. Molecular passage occurs mostly by passage diffusion. Hydration swells the stratum corneum, loosening its normally tight, densely packed arrangement, thus making diffusion easier.

43 Dermatitis and Dry Skin
Dermatitis is a nonspecific term that describes a vast number of dermatological conditions that are inflammatory and generally characterized by erythema. The terms dermatitis and eczema are often used interchangeably to describe a group of inflammatory skin conditions of unknown cause. When the cause of a particular skin condition is known, the disorder is given a specific name. Known causes of dermatitis include allergens, irritants, and infections. Dry skin (xerosis) is a common occurrence is almost everyone. It may be seasonal in some, and chronic for others. Often not serious, but annoying and uncomfortable because of pruritis. Some may have pain and inflammation. Dry skin is more prone to bacterial invasion than normal skin.

44 Atopic Dermatitis Occurs most often in infants, children, and young adults. Most common dermatological condition seen in young children. In adults it is often associated with other skin conditions. Areas commonly affected (face, flexural areas on inside of knees and elbows, and collar area of neck) depend on the patient’s age. “Atopy” means not in the right place. No diagnostic lab tests exist, though there may be elevated IgE and eosinophil levels. May be accompanied by allergic respiratory disease, but atopic dermatitis is often the initial clinical manifestation of an allergic disease.

45 Atopic Dermatitis Common exacerbating factors include soaps, detergents, temperature changes, mold, dust, pollens, and emotional changes. Thought to be genetically linked. 25% risk if one parent has it, > 50% if both parents have atopic dermatitis. Typically appears in the first year of life, as redness and chapping of the infant’s cheeks, which may continue to affect the face, neck, and trunk. May progress to become more generalized with crusting developing on the forehead or cheeks. Result of dried exudate containing proteinaceous and cellular debris from erosion or ulceration of primary skin lesions. Primary symptom is severely intense pruritic papules (solid, round, and elevated lesions less than 1cm in diameter). Affected skin can progress to erythematous, excoriated, and scaling lesions. After repeated scratching and itching, the skin becomes thick, or lichenified.

46 Atopic Dermatitis Source:

47 Treatment of Atopic Dermatitis
Goals in treatment: 1. Maintain skin hydration, 2. Relieve or minimize symptoms of itching and weeping, 3. Avoid or minimize factors that trigger or aggravate the disorder. Skin hydration through use of emolients and moisturizers. Hydrocortisone can help prevent itching and weeping. See HCP if patient is less than 2 yr. old, or if condition is severe or involves large area of body.

48 Contact Dermatitis Refers to a rash that results from an allergen or irritant in contact with susceptible skin. Often the result of exposure to occupational irritants. Usually occurs in children over 8yr old. Irritant contact dermatitis is nonallergic and nonimmunologic reaction caused by exposure to irritating substances. Often occupation-related and commonly seen in patients who work in food, plastics, oil, agriculture, or construction industries. Irritant generally elicits a response on first exposure. Injury it causes to the skin may not be limited to erythema and vesiculation, but may result in ulceration and tissue necrosis. Mild irritants generally require repeated or extended contact to cause a significant inflammatory response. Acute irritation is more likely if the area is under occlusion, which minimizes evaporation and causes the skin to become more permeable to chemicals. Gloves, clothing, and diapers often increase susceptibility and should be changed often.

49 Contact Dermatitis Some agents may act as sensitizers: iodine containing antiseptics, latex, formaldehyde, benzocaine, PABA, topical diphenhydramine (Benadryl®). Allergic contact dermatitis is immunologically mediated and is manifested by a delayed-hypersensitivity reaction to contact allergens. Involves contact of the skin with an allergenic material acting as a hapten, which becomes attached to protein carriers on specific cells in the epidermis. Initial sensitizing exposure is necessary for the reaction to occur. On subsequent contact with the allergen, reactive skin areas typically present as eczema – appearing within minutes to hours after exposure. Example: poison ivy. Hands are most often involved in adults, particularly on the backs of the hands. Can occur on the upper back, thighs, axillary areas, feet, and face. Lesions are often asymmetric and well-defined, reflecting where contact with the substance occurred.

50 Contact Dermatitis from Shoes

51 Treatment of Contact Dermatitis
Decreasing exposure to irritants such as detergents, soaps, and solvents is a good preventative measure. Mild-to-moderate contact dermatitis usually amenable to treatment with nonprescription agents. Astringents such as aluminum acetate can dry lesions (Apply 20min, 4 times a day). Calamine and colloidal oatmeal can relieve itching. Hydrocortisone reduces erythema. Systemic antihistamines such as diphenhydramine and chlorpheniramine may relieve itching and help with sleep. Duration of therapy is usually short because the condition usually improves upon withdrawal of the allergen or irritant, typically within hours.

52 Products for Atopic Dermatitis, Contact Dermatitis, and Dry Skin
Bath oils consist of a mineral or vegetable oil, plus a surfactant. Mineral oil is better adsorbed on the skin than vegetable oil. Only minimally effective in improving dry skin because they are greatly diluted in water. Effect may be enhanced by adding oil at end of bath, and patting skin dry instead of rubbing it. Make tub and floor slippery, creating a safety hazzard especially for the elderlyor children. Make cleansing the skin with soaps more difficult. Colloidal oatmeal bath products (Aveeno®) contain starch, protein, and a small amount of oil. Less effective at moisturizing than bath oils, but have antipruritic effect. May clog bath pipes if used on a regular basis.

53 Emollients/Moisturizers
Most commonly used emollients include petrolatum and mineral oil. Attempt to formulate products that try to function like sebum. Sometimes try to use exotic oils to mimic lipid content, but petrolatum works best. Emollients are occlusive agents and moisturizers that are used to prevent or relieve the signs and symptoms of dry skin. Act by leaving an oily film behind on skin surface through which moisture can not readily escape. Some HCPs believe that emollients alone are not enough to maintain adequate skin hydration. A patient may be advised to hydrate the skin by soaking in water for 5-10 minutes, patting the skin dry, and applying an occlusive agent while the skin is still damp. Drinking plenty of water should also be stressed.

54 Humectants Humectants are hydrating agents that attract water. Often added to emollient base to draw water into the skin. Used alone they can evaporate water out of stratum corneum. Examples are glycerin, propylene glycol, and phospholipid products like lecithin.

55 Keratin-Softening Agents
Chemically alter the keratin layer to soften skin and cosmetically improve its appearance. Dry skin symptoms will not be improved without adding water to the stratum corneum. Urea in concentrations of 10-30% is mildly keratolytic and increases water uptake into the stratum corneum. Is able to remove crusted necrotic tissue at higher concentrations, however causes stinging, burning and irritation particularly on broken skin. Lactic acid is useful for treating dry skin at concentrations of 2-5%. Increases hydration of human skin, and acts as a modulator of keratinization rather than a keratinolytic agent. Added to urea to stabilize effects on skin and for hydration. Allantoin is also a keratin softening agent, works by disrupting the structure. Generally less effective than urea for softening skin.

56 Astringents Retard oozing, discharge, or bleeding of dermatitis when applied to unhealthy skin or mucous membranes. Work by coagulating proteins. When applied as a wet dressing or compress, they cool and dry the skin through evaporation. Act as vasoconstrictors and reduced blood flow to inflamed tissue, and cleanse the skin of exudates, crust, and debris. Have a low cell permeability so activity is limited to the cell surface and interstitial spaces. Examples are aluminum acetate and witch hazel. Patient may soak affected area in astringent solution two to four times daily for 15 to 30 minutes.

57 Topical Hydrocortisone
Only corticosteroid available without a prescription for topical treatment of dermatitis. Available 0.5%, 1% creams, ointments, sprays. Exact mechanism of action is unknown, it relieves redness, heat, pain, swelling, and itch associated with many dermatoses, possibly due to a vasoconstrictive effect. Apply sparingly to affected area three to four times a day. Make sure that infection is not present (bacterial or fungal), HC masks the signs of infection, allowing it to progress without patient knowing. Ask pharmacist if you are unsure. Do not use for prolonged periods of time. Response decreases over time, and skin atrophy may occur because of inhibited collagen production.


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