Commentary
Seborrheic Dermatitis Guy Webster, M.D., Ph.D.
Seborrheic dermatitis is an extraordinarily common skin disease about which little is known. Indeed, the depth and extent of our knowledge of seborrheic dermatitis is not much greater than the original description provided by Sabouraud. Animal models are lacking and there is no real consensus as to the nature of the disease. The name itself is a misnomer because the role of sebum in seborrheic dermatitis is doubtful. Sebaceous output is not elevated and suppression of sebum fails to diminish the disease.''^ Many believe that seborrheic dermatitis is actually dandruff of the face because thefinescale seen in seborrheic dermatitis is similar to that seen on the scalp with dandruff. Despite this gross similarity, there are clear differences in these two diseases.' The most notable difference is that seborrheic dermatitis has much greater clinical evidence of infiammation than dandrufT, which is usually noninflammatory. Inflammatory or Infectious
The simplest question awaiting an answer is whether the basic process is infiammatory or infectious. For many years the yeast Pityrosporum ovafe(some authorities prefer the designation Malassezia furfur) has been incriminated as the cause of seborrheic dermatitis. This yeast is a member of the normal flora of sebaceous regions, particularly the head, and is present in large numbers in all adults regardless of whether they have seborrheic dermatitis. Tinea versicolor is a clear example of P. ovale infection; it bears little clinical resemblance to seborrheic dermatitis. Nevertheless, there is still great interest in linking P. ovale to seborrheic dermatitis. Groisser and associates' have found that patients with acquired immunodeficiency syndrome have more From the Department of Dermatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania. Address correspondence to; Guy Webster, M.D., Ph.D., Department of Dermatology, Jefferson Medical College, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107.
December 1991, Vol. 30, No. 12
P. ovale on their facial scale from sites with seborrheic dermatitis than from areas with no disease. Such circumstantial evidence is clearly not proof of involvement and has not been confirmed by recent studies." A comparable situation occurs in eczema and psoriasis. When Staphylococcus aureus is quantified in these diseases, elevated populations are found, but it is generally agreed that staphylococcal colonization is not central to either disease process. Antifungal Agents
A group of studies that have some bearing on this issue were largely designed to test the effectiveness of antifungal drugs in the treatment of seborrheic dermatitis.'"* The drug that has usually been used is ketoconazole, an imidazole derivative that is active against Pityrosporum yeasts both in vitro and in vivo. Although these studies are often cited as evidence for the central role of P. ovale in seborrheic dermatitis, they are somewhat remarkable for the number of partial responses seen. Complete resolution was not the rule. It should be kept in mind that statistics are not needed to show that topical ketoconazole is effective in tinea versicolor or that penicillin will cure a streptococcal infection. Explanations for the beneficial effect of imidazoles on seborrheic dermatitis that do not involve P. ovale are lacking. Perhaps the drug possesses antiinfiammatory properties that have yet to be appreciated. An alternative hypothesis suggests that seborrheic dermatitis represents immune hypersensitivity to P. ovale. This approach may explain the response to ketoconazole but fails to account for the distribution of lesions, the observation that patients with a failing immune system often have the worst seborrheic dermatitis, and the waxing and waning nature of most cases for a period of many years. The report by Wishner et al. shed further doubt on the central role of P. ovale in seborrheic dermatitis.' In their study, 117 patients who were infected with the human immunodeficiency virus were examined for the 843
844
International Journal of Dermatology • December 1991
Vol. 30
presence of seborrheic dermatitis. Many of these patients were receiving long-term treatment with oral ketoconazole for fungal infections. There was no significant difference in the incidence of seborrheic dermatitis in patients who had received ketoconazole compared with those who had not. Taken together, the literature seems most consistent with the concept that yeasts of the Pityrosporum genus may at most exacerbate seborrheic dermatitis, perhaps in a manner similar to the involvement of S. aureus in atopic dermatitis. The observation that low potency topical corticosteroids are effective in treating seborrheic dermatitis* also argues against the primary involvement of P. ovale since one would expect a fungal disease to be exacerbated by steroid suppression of inflammation.
sponse is blocked by capsaisin or deenervation of either limb."-'" Although it is clear that seborrheic dermatitis is not part of reflex sympathetic dystrophy and a direct extrapolation of reflex neurogenic inflammation is not warranted, the increased incidence of seborrheic dermatitis in central nervous system disease may point to another manifestation of neural-induced inflammation on the skin. Modulation of seborrheic dermatitis by the nervous system might account for the unusual facial distribution of lesions. A neural influence in seborrheic dermatitis is also consistent with the often incomplete response to anti-Pityrosporum therapy and the generally favorable response to mild corticosteroids.
Neural Influence
References
A valuable clue to the true cause of seborrheic dermatitis may be found in the diseases with which it is associated, most notably acquired immunodeficiency syndrome and neurologic disease. Patients who are infected with the human immunodeficiency virus may have an incidence rate as high as 50% for seborrheic dermatitis.'" Diseases of the central nervous system, particularly Parkinsonism, are clearly associated with an increased incidence and severity of seborrheic dermatitis." This increase seems to be unrelated to factors of general physical health and hygiene. A report of unilateral seborrheic dermatitis after nerve injury emphasizes the potential role of neural involvement.'^ It is distinctly possible that there is more neural influence on the skin than has been previously suspected. The best suggestions of this interaction come from the study of reflex sympathetic dystrophy. Reflex sympathetic dystrophy is a poorly understood syndrome of chronic posttraumatic pain." Initial cutaneous phases of the disease primarily involve changes in peripheral vascular activity believed to be caused by sympathetic nervous system aberrations. Dysesthesia and hyperalgesia are marked in all phases and as disease progresses there may be unmistakable evidence of cutaneous atrophy. The distribution of these skin changes may be well defined, suggesting a dermatomal distribution. The cause of reflex sympathetic dystrophy is not known and is believed to be related to the poorly understood phenomenon of reflex neurogenic inflammation. There are several animal studies that demonstrate that injury to one limb can result in inflammation in the contralateral limb. This inflammatory re-
1. Kligman AM, Leyden JJ. Seborrheic dermatitis. Semin Dermatol. 1983;2;57-59. 2. Pye RJ, Meyrich G, Burton JL. Skin surface lipids in seborrheic dermatitis. BrJ Dermatol. 1977;97(suppl);f2-15. 3. Groisser D, Bottone EJ, Lebwohl M. Association of Pityrosporum orbicutare {Malassezia furfur) with seborrheic dermatitis in patients with acquired immunodeficiency syndrome. J Am Acad Dermatol. 1989;20;770-773. 4. Bergbrant I-M, Faergemann J. The role o(Pityrosporum ovale in seborrheic dermatitis. Semin Dermatol. I990;9;262-268. 5. Skinner RB, Noah PW, Taylor NM, et al. Double blind treatment of seborrheic dermatitis with 2% ketoconazole cream. J Am Acad Dermatol. 1985;12;852-B56. 6. Stratigos JD, Antonion C, Katsambas A, et al. Ketoconazole 2% cream versus hydrocortisone 1 % cream in the treatment of seborrheic dermatitis. J Am Acad Dermatol. 1988;19;85-853. 7. Green CA, Farr PM, Shuster S. Treatment of seborrheic dermatitis with ketoeonazole II; Response of seborrheic dermatitis of the face, scalp and trunk. BrJ Dermatol. I987;l 16;2I7-221. 8. Ruiz-Maldonado R, Lopez-Matinez R, Perez-Clavanna EL, et al. Pityrosporum ovale in infantile seborrheic dermatitis. Pediatr Dermatol. 1989;6; 16-20. 9. Wishner AJ, Teplitz ED, Goodman DS. Pityrosporum, ketoconazole and seborrheic dermatitis. J Am Acad Dermatol. 1987;17;140-141. 10. Mathes BM, Douglass MC. Seborrheic dermatitis in patients with acquired immunodeficiency syndrome. J Am Acad Dermatol. 1985;13;947-951. 11. Binder RL, Jonelis FJ. Seborrheic dermatitis in neuroleptic-induced Parkinsonism. Arch Dermatol. 1983;119;473-435. 12. Bettley FR, Martin RH. Unilateral seborrheic dermatitis following a nerve lesion. Arch Dermatol. I956;73;l 10-115. 13. Schwartzman RJ, McClellan TL. Reflex sympathetic dystrophy; A review. Arch Neurol. 1987;44;555-56I. 14. Levine JD, Dardick SJ, Basbaum Al, et al. Reflex neurogenic inflammation; I. Contribution of the peripheral nervous system to spatially remote inflammatory responses that follow injury. J Neurosci. 1985;5;l38O-1386.
Seborrheic Dermatitis Guy Webster, M.D., Ph.D.
Seborrheic dermatitis is an extraordinarily common skin disease about which little is known. Indeed, the depth and extent of our knowledge of seborrheic dermatitis is not much greater than the original description provided by Sabouraud. Animal models are lacking and there is no real consensus as to the nature of the disease. The name itself is a misnomer because the role of sebum in seborrheic dermatitis is doubtful. Sebaceous output is not elevated and suppression of sebum fails to diminish the disease.''^ Many believe that seborrheic dermatitis is actually dandruff of the face because thefinescale seen in seborrheic dermatitis is similar to that seen on the scalp with dandruff. Despite this gross similarity, there are clear differences in these two diseases.' The most notable difference is that seborrheic dermatitis has much greater clinical evidence of infiammation than dandrufT, which is usually noninflammatory. Inflammatory or Infectious
The simplest question awaiting an answer is whether the basic process is infiammatory or infectious. For many years the yeast Pityrosporum ovafe(some authorities prefer the designation Malassezia furfur) has been incriminated as the cause of seborrheic dermatitis. This yeast is a member of the normal flora of sebaceous regions, particularly the head, and is present in large numbers in all adults regardless of whether they have seborrheic dermatitis. Tinea versicolor is a clear example of P. ovale infection; it bears little clinical resemblance to seborrheic dermatitis. Nevertheless, there is still great interest in linking P. ovale to seborrheic dermatitis. Groisser and associates' have found that patients with acquired immunodeficiency syndrome have more From the Department of Dermatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania. Address correspondence to; Guy Webster, M.D., Ph.D., Department of Dermatology, Jefferson Medical College, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107.
December 1991, Vol. 30, No. 12
P. ovale on their facial scale from sites with seborrheic dermatitis than from areas with no disease. Such circumstantial evidence is clearly not proof of involvement and has not been confirmed by recent studies." A comparable situation occurs in eczema and psoriasis. When Staphylococcus aureus is quantified in these diseases, elevated populations are found, but it is generally agreed that staphylococcal colonization is not central to either disease process. Antifungal Agents
A group of studies that have some bearing on this issue were largely designed to test the effectiveness of antifungal drugs in the treatment of seborrheic dermatitis.'"* The drug that has usually been used is ketoconazole, an imidazole derivative that is active against Pityrosporum yeasts both in vitro and in vivo. Although these studies are often cited as evidence for the central role of P. ovale in seborrheic dermatitis, they are somewhat remarkable for the number of partial responses seen. Complete resolution was not the rule. It should be kept in mind that statistics are not needed to show that topical ketoconazole is effective in tinea versicolor or that penicillin will cure a streptococcal infection. Explanations for the beneficial effect of imidazoles on seborrheic dermatitis that do not involve P. ovale are lacking. Perhaps the drug possesses antiinfiammatory properties that have yet to be appreciated. An alternative hypothesis suggests that seborrheic dermatitis represents immune hypersensitivity to P. ovale. This approach may explain the response to ketoconazole but fails to account for the distribution of lesions, the observation that patients with a failing immune system often have the worst seborrheic dermatitis, and the waxing and waning nature of most cases for a period of many years. The report by Wishner et al. shed further doubt on the central role of P. ovale in seborrheic dermatitis.' In their study, 117 patients who were infected with the human immunodeficiency virus were examined for the 843
844
International Journal of Dermatology • December 1991
Vol. 30
presence of seborrheic dermatitis. Many of these patients were receiving long-term treatment with oral ketoconazole for fungal infections. There was no significant difference in the incidence of seborrheic dermatitis in patients who had received ketoconazole compared with those who had not. Taken together, the literature seems most consistent with the concept that yeasts of the Pityrosporum genus may at most exacerbate seborrheic dermatitis, perhaps in a manner similar to the involvement of S. aureus in atopic dermatitis. The observation that low potency topical corticosteroids are effective in treating seborrheic dermatitis* also argues against the primary involvement of P. ovale since one would expect a fungal disease to be exacerbated by steroid suppression of inflammation.
sponse is blocked by capsaisin or deenervation of either limb."-'" Although it is clear that seborrheic dermatitis is not part of reflex sympathetic dystrophy and a direct extrapolation of reflex neurogenic inflammation is not warranted, the increased incidence of seborrheic dermatitis in central nervous system disease may point to another manifestation of neural-induced inflammation on the skin. Modulation of seborrheic dermatitis by the nervous system might account for the unusual facial distribution of lesions. A neural influence in seborrheic dermatitis is also consistent with the often incomplete response to anti-Pityrosporum therapy and the generally favorable response to mild corticosteroids.
Neural Influence
References
A valuable clue to the true cause of seborrheic dermatitis may be found in the diseases with which it is associated, most notably acquired immunodeficiency syndrome and neurologic disease. Patients who are infected with the human immunodeficiency virus may have an incidence rate as high as 50% for seborrheic dermatitis.'" Diseases of the central nervous system, particularly Parkinsonism, are clearly associated with an increased incidence and severity of seborrheic dermatitis." This increase seems to be unrelated to factors of general physical health and hygiene. A report of unilateral seborrheic dermatitis after nerve injury emphasizes the potential role of neural involvement.'^ It is distinctly possible that there is more neural influence on the skin than has been previously suspected. The best suggestions of this interaction come from the study of reflex sympathetic dystrophy. Reflex sympathetic dystrophy is a poorly understood syndrome of chronic posttraumatic pain." Initial cutaneous phases of the disease primarily involve changes in peripheral vascular activity believed to be caused by sympathetic nervous system aberrations. Dysesthesia and hyperalgesia are marked in all phases and as disease progresses there may be unmistakable evidence of cutaneous atrophy. The distribution of these skin changes may be well defined, suggesting a dermatomal distribution. The cause of reflex sympathetic dystrophy is not known and is believed to be related to the poorly understood phenomenon of reflex neurogenic inflammation. There are several animal studies that demonstrate that injury to one limb can result in inflammation in the contralateral limb. This inflammatory re-
1. Kligman AM, Leyden JJ. Seborrheic dermatitis. Semin Dermatol. 1983;2;57-59. 2. Pye RJ, Meyrich G, Burton JL. Skin surface lipids in seborrheic dermatitis. BrJ Dermatol. 1977;97(suppl);f2-15. 3. Groisser D, Bottone EJ, Lebwohl M. Association of Pityrosporum orbicutare {Malassezia furfur) with seborrheic dermatitis in patients with acquired immunodeficiency syndrome. J Am Acad Dermatol. 1989;20;770-773. 4. Bergbrant I-M, Faergemann J. The role o(Pityrosporum ovale in seborrheic dermatitis. Semin Dermatol. I990;9;262-268. 5. Skinner RB, Noah PW, Taylor NM, et al. Double blind treatment of seborrheic dermatitis with 2% ketoconazole cream. J Am Acad Dermatol. 1985;12;852-B56. 6. Stratigos JD, Antonion C, Katsambas A, et al. Ketoconazole 2% cream versus hydrocortisone 1 % cream in the treatment of seborrheic dermatitis. J Am Acad Dermatol. 1988;19;85-853. 7. Green CA, Farr PM, Shuster S. Treatment of seborrheic dermatitis with ketoeonazole II; Response of seborrheic dermatitis of the face, scalp and trunk. BrJ Dermatol. I987;l 16;2I7-221. 8. Ruiz-Maldonado R, Lopez-Matinez R, Perez-Clavanna EL, et al. Pityrosporum ovale in infantile seborrheic dermatitis. Pediatr Dermatol. 1989;6; 16-20. 9. Wishner AJ, Teplitz ED, Goodman DS. Pityrosporum, ketoconazole and seborrheic dermatitis. J Am Acad Dermatol. 1987;17;140-141. 10. Mathes BM, Douglass MC. Seborrheic dermatitis in patients with acquired immunodeficiency syndrome. J Am Acad Dermatol. 1985;13;947-951. 11. Binder RL, Jonelis FJ. Seborrheic dermatitis in neuroleptic-induced Parkinsonism. Arch Dermatol. 1983;119;473-435. 12. Bettley FR, Martin RH. Unilateral seborrheic dermatitis following a nerve lesion. Arch Dermatol. I956;73;l 10-115. 13. Schwartzman RJ, McClellan TL. Reflex sympathetic dystrophy; A review. Arch Neurol. 1987;44;555-56I. 14. Levine JD, Dardick SJ, Basbaum Al, et al. Reflex neurogenic inflammation; I. Contribution of the peripheral nervous system to spatially remote inflammatory responses that follow injury. J Neurosci. 1985;5;l38O-1386.
