Manual of Dermatologic Therapeutics
7th Edition
© 2007 Lippincott Williams & Wilkins
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29
Seborrheic Dermatitis and Dandruff
Penpun Wattanakrai
I. Definition and Pathophysiology
Seborrheic dermatitis and dandruff both cause a scaling on the scalp that is often associated with itching. There are, however, distinctions between the two disorders. Dandruff is a noninflammatory form of seborrheic dermatitis with increased scaling on the scalp that represents the more active end of the spectrum of physiologic desquamation. On a normal scalp, approximately 487,000 cells/sq cm can be found after a detergent scrub; scalps affected with dandruff and seborrheic dermatitis liberate up to 800,000 cells/sq cm. Therefore, we will consider seborrheic dermatitis and dandruff to be manifestations of different severities of a similar origin.
Seborrheic dermatitis is an inflammatory, erythematous, and scaling eruption that occurs primarily in “seborrheic” areas, that is, those with a high number and activity of sebaceous glands, such as the scalp, face, and upper trunk. Although seborrheic dermatitis occurs in neonatal and postpubertal life—times during which sebaceous glands are most active—no direct relationship between the amount or composition of sebum and the presence of dermatitis has been documented. This disease is one of accelerated epidermal growth resulting in retention of nuclei in stratum corneum cells that have not had sufficient time to completely mature. On a normal scalp, there are approximately 3,700 nucleated cells/sq cm; on scalps with dandruff, there are 25,000; and on those with seborrheic dermatitis, the count is 76,000.
The etiologic agents involved in seborrheic dermatitis are multifactorial including the presence of sebum, the Malassezia (previously Pityrosporum) yeast, lipase activity, immune function, atmospheric humidity, and stress (1). Although seborrheic dermatitis occurs in skin areas with active sebaceous glands, the amount of sebum production does not directly correlate with the presence or severity of seborrheic dermatitis. Patients produce no more sebum on their scalps than controls, and reducing sebum excretion affects neither dandruff nor seborrheic dermatitis. The severity may be related to the composition of the sebum lipids or the lipase enzyme activity of Malassezia and/or Propionibacterium acnes. These lipase enzymes may split triglycerides into irritating fatty acids or release arachidonic acid, which may cause cutaneous inflammation.
The genus Malassezia, a lipophilic yeast, is currently classified into nine known species. Seven of the Malassezia yeasts, which are normal inhabitants of the skin, have been hypothesized to be the etiologic agents in seborrheic dermatitis. Although the absolute level of yeasts does not correlate with seborrheic dermatitis, its reduction in individuals with the disease does improve the symptoms. High yeast densities can also be present without symptoms. Different Malassezia subtypes may be more pathogenic. Malassezia globosa (originally described as Pityrosporum orbiculare) and Malassezia restricta (visually resembling Pityrosporum ovale) are most commonly found to be associated with seborrheic dermatitis (2). However, other investigators have also found Malassezia furfur, Malassezia sympodialis, Malassezia obtuse, and Malassezia slooffiae, depending on the population and geographic area studied (3). Malassezia has been cultured in 73% of infants with seborrheic dermatitis; the yeast may be cultured from the scalp, face, and presternal or inguinal region. Despite the many variable data found when measuring fungal load, more direct support comes from the many reports that demonstrate the response of seborrheic dermatitis to oral and topical antifungals that effectively decrease the number of Malassezia yeasts.
Abnormal immune response or inflammatory reaction to Malassezia may also be an important etiologic factor in seborrheic dermatitis. Interleukin 2 (IL-2) and interferon-γ (IFN-γ) production by lymphocytes are decreased, and there is an associated increase
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in production of IL-10 and immunoglobulin E (IgE) synthesis. T-cell function may be depressed and there may be an increase in the number of natural killer cells, or level of serum IgA and IgG (4). Malassezia antigens have been demonstrated to sensitize some patients, resulting in increased IgG levels, whereas others show conflicting results that elevated IgG titers are not related to Malassezia (5,6). Most adult patients with atopic dermatitis of the scalp and facial region are prick test positive to P. ovale (7). Strong inflammatory reactions may also be involved in seborrheic dermatitis. Malassezia can activate complement by both the classic and the alternative pathway and can also induce human keratinocyte cytokine production (8). The inflammation in seborrheic dermatitis may be irritant or nonimmunogenic caused by the composition of the sebum lipids or by the lipase enzyme activity or by the toxic metabolites produced by Malassezia.
There is a significantly increased incidence, often with extensive and severe seborrheic-like dermatitis, in human immunodeficiency virus (HIV)-positive patients and patients with acquired immunodeficiency syndrome (AIDS), ranging from 30% to 83% (9,10,11). Also noted is the increased incidence of seborrheic dermatitis in Parkinson’s disease (idiopathic and drug induced) and other neurologic disorders. It has been theorized that there is an increased rate of sebum excretion secondary to either overactivity of the parasympathetic nervous system or action of androgens or melanocyte-stimulating hormone (MSH) (12). Other diseases associated with seborrheic dermatitis are depression, mood disorders, and pityriasis versicolor. Areas of increased skin temperature on facial skin, as documented by a sensitive thermal imager, are sites that are predisposed to seborrheic dermatitis (13). The condition is more common in male patients than in female patients and occurs most frequently in adolescents and young adults and again in adults older than 50 years. A familial tendency toward seborrheic dermatitis and an increased incidence of allergy within the family are usually present.
II. Subjective Data
The lesions of seborrheic dermatitis and dandruff are often asymptomatic with a mild clinical course. Episodic variation in intensity is common, often being precipitated by tiredness, stress, or cold weather. Pruritus is not uncommon and may be intense at times.
III. Objective Data
  • Dandruff appears simply as noninflammatory, diffuse white or greasy scaling on the scalp usually without significant erythema or inflammation.
  • In seborrheic dermatitis of the scalp, there is more pruritus and inflammation. The vertex and parietal regions are commonly affected. The borders of erythema and scaling are sharply demarcated and may be seen at or beyond the frontal hairline called the corona seborrheica.
  • With facial seborrheic dermatitis, there is erythema, scaling, and at times exudation; the borders may be well defined. Mild erythema and fine, dry scaling may also be found on the eyebrows, eyelids, nasolabial and postauricular folds, moustache, beard, and presternal areas. The intertriginous areas, the inframammary folds, groin, gluteal crease, and umbilicus are also affected. Lesions may become thick, semiconfluent, yellow, and greasy. Secondary impetiginization and folliculitis may occur. Seborrheic dermatitis may be a cause of a generalized exfoliative erythroderma.
  • Seborrheic marginal blepharitis, which consists of erythema and scaling of eyelid margins and cilia, is often associated with mild granular conjunctivitis or ocular irritation. Seborrheic dermatitis in other sites is often not present. Seborrheic dermatitis may also be associated with ocular rosacea.
  • Infantile seborrheic dermatitis is self-limited and confined to the first 3 months of life. It usually starts approximately 1 week after birth and is characterized by erythema and scaling plaques involving the scalp, diaper region, or flexural surfaces; when the vertex of the scalp is involved, the condition is known as cradle cap. Generalized seborrheic dermatitis–like exfoliative dermatitis in an infant accompanied with systemic signs and symptoms such as fever, anemia, diarrhea, weight loss, failure to thrive, and infections is referred to as Leiner’s syndrome. Originally reported as a disorder due to dysfunctional C5, it may be a clinical manifestation of various immunodeficiency disorders including defective phagocytic function, defect
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    in the third component of complement system, severe combined immunodeficiency, hypogammaglobulinemia, and hyperimmunoglobulinemia E (14).
  • Drug eruptions from gold, methyldopa, chlorpromazine or cimetidine therapy, or vitamin B deficiency may mimic seborrheic dermatitis.
  • In chronic cases, nonscarring alopecia can be noted secondary to the inflammation and the secondary effects of scratching. This should be reversible with treatment.
IV. Therapy
Treatment modalities in seborrheic dermatitis mainly target the three important etiologic factors implicated in the disease and include keratolytic agents and antiinflammatory and antifungal preparations.
  • Agents effective in eliminating the scaling of dandruff and seborrheic dermatitis appear to act by varying mechanisms. Selenium sulfide and tars inhibit mitotic activity, and selenium kills yeasts as well. Zinc pyrithione is directly cytotoxic and has antimicrobial effects, and salicylic acid disrupts the bonds that cause stratum corneum cells to stick together. There are no studies comparing the efficacy of antiseborrheic shampoos. The following agents are listed in rough approximation of usefulness:
    • Ketoconazole is available as a 2% cream, a 2% shampoo, an oil-in-water emulsion, and a foaming gel. The 2% ketoconazole (Nizoral) shampoo is used at least twice weekly for 2 to 4 weeks, leaving the product on for 5 minutes. Placing the suds on areas of facial involvement is also helpful. Once the dermatitis is under control, treatment once a week helps prevent relapse. A 1% preparation is now available over the counter. Topical ketoconazole has been studied in children and shown to be effective and well tolerated. Its efficacy is approximately equivalent to that of 1% hydrocortisone cream. Oral ketoconazole has many potential adverse reactions and its use is warranted in only unresponsive cases.
    • A shampoo containing 0.1% triamcinolone applied on a daily basis for 2 weeks can significantly reduce scaling and itching. A maintenance regimen or an alternating schedule with another antidandruff shampoo can then be undertaken.
    • Shampoos containing 2.5% selenium sulfide (Selsun) should be applied two to three times weekly for 5 to 10 minutes each time. Studies have shown no significant difference between the efficacy of selenium sulfide shampoos and ketoconazole shampoo (15).
    • Preparations containing 1% to 2% zinc pyrithione (Danex, DHS Zinc, Head & Shoulders, Zincon) work almost as well. They are also available in a cream formulation.
    • Bifonazole 1% shampoo is a safe and effective treatment for seborrheic dermatitis of the scalp in infants and children (16).
    • Salicylic acid-sulfur shampoos (Ionil, Sebulex) are less effective.
    • Tar shampoos (DHS-T, Ionil T, Pentrax, Sebutone, T/Gel, Zetar) inhibit epidermal proliferation through cytostatic effects after an initial burst of transient hyperplasia.
    • Chloroxine (Capitrol) shampoo contains a synthetic antibacterial compound similar to the hydroxyquinoline compounds used in dermatology for many years. Comparative efficacy studies with this shampoo are unavailable.
    • Any nonmedicinal shampoo, particularly those containing surfactants and detergents, will remove scales and lead to subjective clinical improvement and decreased desquamation for approximately 4 days. These agents should be used every 2 days to control dandruff.
    • Alcohol-based preparations and hair tonics should be avoided.
  • If the lesions are extensive or very inflammatory, the patient may apply a topical corticosteroid solution, lotion, or spray (betamethasone valerate or dipropionate lotion is generally effective; other corticosteroid lotions are also useful). Alternatively, a 10% sodium sulfacetamide lotion b.i.d. to t.i.d. may be used. Topical steroid mousse formulations betamethasone valerate (Luxiq) and clobetasol (Olux) are helpful adjuncts for scalp seborrheic dermatitis because the foam melts at skin surface temperature, leaving minimal residue and with no affect on hair styling.
  • Thick crusts may be removed more easily by overnight applications of a keratolytic gel, for example, salicylic acid (Keralyt), with or without plastic cap occlusion;
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    3% sulfur, 3% salicylic acid, 4% cetyl alcohol-coal tar distillate (Pragmatar) cream; Baker’s P&S liquid) or a 30-minute compress with warm mineral oil before shampooing.
  • Seborrheic dermatitis lesions on other areas respond rapidly to a corticosteroid cream such as 1% hydrocortisone applied one to three times a day. Aerosols or lotions are easier to apply to hairy areas. Prolonged application of high-potency fluorinated corticosteroids may lead to disfiguring telangiectasia and atrophy. Other useful topical agents for glabrous skin include sulfur-containing medications such as 10% sulfacetamide lotion; formulations such as precipitated sulfur 3% to 10%, salicylic acid 1% to 5%, and tar 2% in an ointment base; or 1% to 3% sulfur in calamine lotion.
  • A new class of topical immunomodulators, the calcineurin inhibitors, are being used with some success for treating seborrheic dermatitis (17,18). Tacrolimus ointment and pimecrolimus cream lack the side effects associated with steroid use and have been demonstrated to have in vitro antifungal effects against Malassezia furfur (19).
  • Aside from the topical azoles, which have fungistatic properties, including ketoconazole, fluconazole, miconazole, other topicals such as topical terbinafine, ciclopirox, and metronidazole has also been shown to benefit in seborrheic dermatitis.
  • A 15% propylene glycol solution applied to the scalp reduced the number of yeasts and improved seborrheic dermatitis in 90% of those treated (20).
  • For widespread or unresponsive cases, short courses of oral antifungal treatment have been shown to be effective. These include oral ketoconazole (200 mg/day for 2 to 4 weeks) (21), oral itraconazole (100 mg/day up to 21 days; 200 mg/day for 1 week) (22), and oral terbinafine at 250 mg/day for 4 to 6 weeks (23,24).
  • Oral isotretinoin reduces sebaceous gland size up to 90% by decreasing proliferation of the basal sebocytes. Sebum lipid synthesis is reduced by as much as 75% after 4 weeks of isotretinoin at a dose as low as 0.1 mg/kg/day. Patients may experience a relapse in their seborrhea for months to years (25).
  • Seborrheic blepharitis is treated one to three times a day with sulfacetamide alone or a 10% sulfacetamide, 0.2% prednisolone, 0.12% phenylephrine suspension (Blephamide, Vasocidin), or similar preparations (Cetapred, Metimyd, Optimyd). It is essential to monitor intraocular tension concurrent with intermittent or chronic steroid therapy in or around the eye. Therefore, it may be more prudent to use either topical tacrolimus or pimecrolimus as alternatives to topical steroids for treatment around the eyes as both have antiinflammatory activity without the side effects associated with long-term corticosteroid use.
  • Ultraviolet light (both UVA and UVB) is inhibitory to the growth of Malassezia. Many individuals note improvement of seborrheic dermatitis during the summer months (26). However, it has also been reported that some patients develop seborrheic dermatitis subsequent to psoralen plus UVA therapy (27).
References
1. Bergbrant IM. Seborrhoeic dermatitis and Pityrosporum yeasts. Curr Top Med Mycol 1995;6:95–112.
2. Gupta AK, Bluhm R, Cooper EA, et al. Seborrheic dermatitis. Dermatol Clin 2003;21:401–412.
3. Nakabayashi A, Sei Y, Guillot J. Identification of Malassezia species isolated from patients with seborrheic dermatitis, atopic dermatitis, pityriasis versicolor and normal subjects. Med Mycol 2000;38:337–341.
4. Bergbrant IM, Johansson S, Robbins D, et al. An immunological study in patients with seborrhoeic dermatitis. Clin Exp Dermatol 1991;16:331–338.
5. Silva V, Fischman O, de Camargo ZP. Humoral immune response to Malassezia furfur in patients with pityriasis versicolor and seborrheic dermatitis. Mycopathologia 1997;139:79–85.
6. Parry ME, Sharpe GR. Seborrhoeic dermatitis is not caused by altered immune response to Malassezia yeast. Br J Dermatol 1998;139:254–263.
7. Faergemann J. Pityrosporum yeasts—what’s new. Mycoses 1997;40(suppl 1):29–32.
8. Watanabe S, Kano R, Sato H, et al. The effects of Malassezia yeasts on cytokine production by human keratinocytes. J Invest Dermatol 2001;116:769–773.
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9. Smith KJ, Skelton HG, Yeager J, et al. Cutaneous findings in HIV-1 positive patients: a 42-month prospective study. J Am Acad Dermatol 1994;31:746–754.
10. Groisser D, Bottone EJ, Lebwohl M. Association of Pityrosporum orbiculare (Malassezia furfur) with seborrheic dermatitis in patients with acquired immunodeficiency syndrome (AIDS). J Am Acad Dermatol 1989;20:770–773.
11. Marino CT, McDonald E, Romano JF. Seborrheic dermatitis in acquired immunodeficiency syndrome. Cutis 1991;48:217–218.
12. Martignoni E, Godi L, Pacchetti C, et al. Is seborrhea a sign of autonomic impairment in Parkinson’s disease? J Neural Transm 1997;104:1295–1304.
13. Hale EK, Bystryn JC. Relation between skin temperature and location of facial lesions in seborrheic dermatitis. Arch Dermatol 2000;136:559–560.
14. Glover M, Atherton DJ, Levinsky RJ. Syndrome of erythroderma, failure to thrive, and diarrhea in infancy: a manifestation of immunodeficiency. Pediatrics 1988;81:66.
15. Danby FW, Maddin WS, Margesson LJ, et al. A randomized, double-blind, placebo-controlled trial of ketoconazole 2% shampoo versus selenium sulfide 2.5% shampoo in the treatment of moderate to severe dandruff. J Am Acad Dermatol 1993;29:1008–1012.
16. Zeharia A, Mimouni M, Fogel A. Treatment with bifonazole shampoo for scalp seborrhea in infants and young children. Pediatr Dermatol 1996;13:151–153.
17. Rigopoulos D, Ioannides D, Kalogeromitros D, et al. Katsambas A pimecrolimus cream 1% vs. betamethasone 17-valerate 0.1% cream in the treatment of seborrhoeic dermatitis. A randomized open-label clinical trial. Br J Dermatol 2004;151(5):1071–1075.
18. Braza TJ, DiCarlo JB, Soon SL, et al. Tacrolimus 0.1% ointment for seborrhoeic dermatitis: an open-label pilot study. Br J Dermatol 2003;148(6):1242–1244.
19. Nakawa H, Etoh T, Yokota Y, et al. Tacrolimus has antifungal activities against Malassezia furfur isolated from healthy adults and patients with atopic dermatitis. Clin Drug Invest 1996;12:245–250.
20. Faergemann J. Propylene glycol in the treatment of seborrheic dermatitis of the scalp: a double-blind study. Cutis 1988;42:69–71.
21. Ford GP, Farr PM, Ive FA, et al. The response of seborrheic dermatitis to ketoconazole. Br J Dermatol 1984;111:603–609.
22. Kose O, Erbil H, Gur AR. Oral itraconazole for the treatment of seborrheic dermatitis: an open, noncomparative trial. J Eur Acad Dermatol Venereol 2005;19(2):172–175.
23. Scapparo E, Quadri G, Virno G, et al. Evaluation of the efficacy and tolerability of oral terbinafine in patients with seborrheic dermatitis: a multicentre, randomized, investigator-blinded, placebo-controlled trial. Br J Dermatol 2001;144:854–857.
24. Vena GA, Micali G, Santoianni P, et al. Oral terbinafine in the treatment of multi-site seborrheic dermatitis: a multicenter, double-blind placebo-controlled study. Int J Immunopathol Pharmacol 2005;18(4):745–753.
25. Orfanos CE, Zouboulis CC. Oral retinoids in the treatment of seborrhoea and acne. Dermatology 1998;196:140–147.
26. Berg M. Epidemiological studies of the influence of sunlight on the skin. Photodermatology 1989;6:80–84.
27. Yegner E. Seborrheic dermatitis of the face induced by PUVA treatment. Acta Derm Venereol 1983;63:335–339.
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