Seborrheic Dermatitis-like and Atopic Dermatitis-like Eruptions in HIV-Infected Patients CLAY J. COCKERELL,
MD
he skin may be the most commonly affected organ in patients with human immunodeficiency virus (HIV) disease. This may be manifested in a number of different ways, ranging from pruritus and generalized xerosis to severe fulminating infections with opportunistic agents. It is incumbent upon all clinicians to be cognizant of this fact, as inspection may lead to early diagnosis of HIV disease and/or early recognition of severe life-threatening illnesses. It has become increasingly recognized that many HIVrelated inflammatory dermatoses may be unusual and not correspond precisely to well-described conditions.’ The clinician must be aware of this, as treatment response may be poor or delayed. Furthermore, patients may be quite symptomatic and suffer worsened quality of life. In this article, two of these conditions will be addressed; specifically, the atopic dermatitis-like and seborrheic dermatitis-like eruptions commonly seen in this patient population.
T
Atopic Dermatitis-Like Eruption Patients with HIV disease, either the full-blown acquired immunodeficiency syndrome (AIDS) or the AIDSrelated complex (ARC), may suffer from the same common inflammatory skin conditions seen in immunocompetent individuals. Because atopic dermatitis is quite a common affliction of the skin, it would be expected to occur in these patients at least as frequently as in normal subjects. As of this writing, there have been no reports that clearly indicate a marked increase in the frequency of atopic dermatitis and/or atopy in HIV-infected patients;
From the Departments ofpathology and Dermufology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas. Address correspondence to Clay J. Cockerell, MD, Division ofDermutopathology, The University of Texas Southwestern Medical Center, 5323 Hurry Hines Boulevard, Sprague Building, Dallas, TX 75235-9072.
0 2991 by Elsevier Science Publishing
Co., Inc.
l
0738-081x/91/$3.50
however, certain atopic dermatitis-like eruptions probably due to abnormal hypersensitivity responses have been demonstrated.1-5 Thus, there are two distinct groups: those with true atopic dermatitis and those with atopic dermatitis-like cutaneous eruptions. Atopic dermatitis is thought to be a manifestation of general hyperresponsiveness of the skin to external and internal stresses. Numerous theories have been evoked about the possible reason for the hyperresponsiveness, ranging from catecholamine and acetylcholine imbalance to abnormal circulating cytokines.6 In patients with HIV disease known to have had pre-existing atopic dermatitis, several different patterns have emerged. One is that of chronic stable atopic dermatitis without exacerbation seen throughout the course of the HIV disease.4 Other patients may develop severe flares of the atopic dermatitis, with progression to erythroderma (Plate 13).’ Response to removal of the precipitating factors such as low humidity and irritation and treatment with topical corticosteroids, creams, and ointments may be of poor efficacy in such cases. Patients are often extremely pruritic and may excoriate the skin extensively, resulting in open wounds that may serve as sites for external infection. Superinfection with herpes simplex virus resulting in Kaposi’s varicelliform eruption, a complication of atopic dermatitis also seen in immunocompetent hosts, may be quite severe in patients with HIV disease.s Furthermore, atopic patients are often chronic carriers of Staphylococcus [IUTCUS and may be at risk for the development of more serious staphylococcal pyoderma and bacteremia (Plate 14). Cultures should be performed to establish staphylococcal carriage and, when present, appropriate antimicrobials should be administered in an attempt to eradicate the carrier status. Application of topical antimicrobials, such as mupirocin, and the oral administration of rifampicin have both been shown to be of some benefit. In addition to exacerbation of atopic dermatitis, a number of patients with HIV disease may develop a dermati-
49
50
COCKERELL
Clinics in Dermatology
1991;9:49-52 tis, which is “atopic dermatitis-like” in nature.*,*,5 Widespread papulovesicular eruptions with scale and crust, accompanied by intense pruriitis and lichenification, may develop in the usual areas of predilection for atopic dermatitis but may also be generalized (Plate 15). There may be other unusual clinical manifestations such as marked hyperkeratosis and desquamation. The development of such unusual inflammatory dermatoses usually correlates with a T-helper cell count of less than 150 cells per mm3, as described by Kaplan.9 Just as with recalcitrant atopic dermatitis, these conditions may be quite refractory to therapy. Of interest, when histologic sections of such eruptions are examined, unusual patterns may be seen. Rather than the usual hyperplastic epidermis with spongiosis and lichenification characteristically seen with atopic dermatitis, patterns such as interface dermatitides with numerous dyskeratotic keratinocytes and granulomatous dermatitides have been noted.‘,1° Explanations for such findings are speculative but may include a manifestation of abnormal circulating cytokines or diminished Langerhans’ cell numbers. Although atopic dermatitis may occur in HIV-infected individuals, as it does in immunocompetent ones, it should be recognized that, when present, the manifestations may be unusual and more severe. In addition, widespread psoriasiform eruptions with features similar to atopic dermatitis may be found; such eruptions may in fact represent other diseases which, for lack of a better term, are often called atopic dermatitis.
Seborrheic
Dermatitis
A seborrheic dermatitis-like eruption is possibly one of the most common cutaneous manifestations of HIV disease.4 In some estimates, it is said to occur in incidences ranging from 32-83% of HIV-infected patients.” The reason for its development is unknown, but it has been postulated to be due to underlying stress, either physical or emotional, and/or overgrowth of Candida albic~ns~~ or Pityrosporum ovale13-15 secondary to the immunocompromise state. Although the seborrheic dermatitis-like condition of HIV infection has features similar to common seborrheic dermatitis, there are, in many cases, distinct differences. Seborrheic dermatitis in patients with HIV disease is characteristically more florid and may be characterized by intense erythema and thick scale distributed not only in the usual “seborrheic dermatitis” areas, but also in other locations16 (Plate 16). The scalp may be involved by thick, scaly, erythematous plaques, with accompanying oozing and weeping (Plate 17). Furthermore, there may be involvement of the intertriginous areas such as the axillae and groin (Plate 18). In some patients, widespread
eruptions may occur leading to diffuse erythroderma. Some cases may be associated with psoriasis, but in most, the characteristic seborrheic dermatitis-like nature of the eruption is maintained. Patients with HIV disease may develop this condition in association with pre-existing seborrheic dermatitis that simply becomes exacerbated, or they may develop it de novo with the onset of HIV disease or its sequelae. Furthermore, the greater the degree of immunodepression, ie, T-helper cell numbers less than 150 mm.3, the greater the tendency for the development of this condition, as well as its becoming more severe. Treatment is usually similar to that used in immunocompetent patients. Application of topical corticosteroid creams and ointments, as well as topical antifungal preparations, has been shown to be effective in some cases; however, in others, the condition is refractory to virtually any therapy. If treatment response is seen, following its discontinuation there may be prompt exacerbation. Scalp disease often requires keratolytic agents and selenium or tar shampoos with accompanying corticosteroid gels or solutions. Even in those cases, treatment response is variable to poor. In some cases, ultraviolet phototherapy may be beneficial. Although this seborrheic dermatitis-like condition may be a severe problem in patients with HIV disease, these individuals may also develop more classic seborrheic dermatitis, which poses little clinical problem and responds well to therapy. Histopathologically, there are some minor distinctions between the seborrheic dermatitis-like condition in HIVinfected individuals and seborrheic dermatitis in immunocompetent persons, l6 There is often a greater degree of parakeratosis, a more dense inflammatory cell infiltrate, and, interestingly, scattered individually necrotic keratinocytes throughout the epidermis. Furthermore, plasma cells may be seen in greater numbers in the HIV-infected.16 The overall pattern is very similar and in some cases identical to common seborrheic dermatitis.”
Conclusion Patients with HIV disease, be it AIDS or ARC, may develop a wide variety of unusual inflammatory dermatoses that may not correspond precisely to well-defined syndromes described in immunocompetent individuals. They may also develop the same eruptions seen in normal hosts, such as atopic dermatitis and seborrheic dermatitis, but these two usually well-defined, easily treated conditions may assume bizarre presentations and severe courses in the HIV-infected individual. It is essential to be aware of these eruptions as they may serve as the initial clue that an individual might be HIV infected.
Clinics in Dermatology 2991;9:49-51
SEBORRHEIC
Drug Names mupirocin: rifampicin:
Bactroban Rifadin, Rifamate,
COCKERELL ERUPTIONS
51
tions in the acquired immune deficiency syndrome: response to recombinant interferon gamma. Br Med J 1987;294:1185-86.
Rimactane
8. Penneys NS. Skin Manifestations of AIDS. Philadelphia, JB Lippincott, 1990, pp 80 - 85.
References 1, Cockerell
CJ, Rao BK. Histologic patterns of unusual inflammatory dermatoses in patients with human immunodeficiency virus infection. (Submitted for publication).
2. Penneys NP, Hicks B. Unusual cutaneous signs of acquired immunodeficiency syndrome. J Am Acad Dermatol 1985;13:845-52. 3. Cockerell CJ, Friedman-Kien AE. Skin manifestations HIV infection. Prim Care 1989;16:621.
AND ATOPIC DERMATITIS-LIKE
of
4 Goodman DS, Teplitz ED, Wishner A, et al. Prevalence of cutaneous disease in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. J Am Acad Dermatol 1987;17:210-20. 5. Kaplan MH, Sadick N, McNutt NS, et al. Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS). J Am Acad Dermatol1987;16:485-506. 6. Zung DYM, Rhodes AR, Geha RS. Atopic dermatitis. In Fitzpatrick TB, Eisen AZ, Wolff K, et al. (eds): Dermatology in General Medicine, 3rd Edition. New York, McGraw-Hill, 1987, pp 1385-1408. 7. Parkin JM, Eales LJ, Galazka AR, et al. Atopic manifesta-
9. Kaplan M. Combined HTLV-HIV infections. Presented at the American Society of Dermatopathology Meeting, Washington, DC, December, 1988. 10. Rico MJ, Cory WP, Gould EW, et al. Interface dermatitis in patients with the acquired immunodeficiency syndrome. J Am Acad Dermatol 1987;16:1209-17. 11. Mathes BM, Douglass MC. Seborrheic tients with acquired immunodeficiency Acad Dermatol 1985;13:947-51.
dermatitis in pasyndrome. J Am
12. Beare JM, Cheeseman EA, MacKenzie DWR. The association between Candida albicans and lesions of seborrheic eczema. Br J Dermatol 1968;80:675-81. 13. Faergemann J, Frederiksson T. Tinea versicolor with regard to seborrheic dermatitis. Arch Dermatol1979;115:966-68. 14. Leyden JJ, McGinley KJ, Kligrnan AM. Role of microorganisms in dandruff. Arch Dermatol 1976;112:333-38. 15. McGinley KJ, Leyden JJ, Marples RR, et al. Quantitative microbiology of the scalp in non-dandruff, dandruff and seborrheic dermatitis. J Invest Dermatol 1975;64:401-05. 16. Soeprono FF, Schinella RA, Cockerell CJ, et al. Seborrheiclike dermatitis of acquired immunodeficiency syndrome. J Am Acad Dermatol 1986;14:242-48.
MD
he skin may be the most commonly affected organ in patients with human immunodeficiency virus (HIV) disease. This may be manifested in a number of different ways, ranging from pruritus and generalized xerosis to severe fulminating infections with opportunistic agents. It is incumbent upon all clinicians to be cognizant of this fact, as inspection may lead to early diagnosis of HIV disease and/or early recognition of severe life-threatening illnesses. It has become increasingly recognized that many HIVrelated inflammatory dermatoses may be unusual and not correspond precisely to well-described conditions.’ The clinician must be aware of this, as treatment response may be poor or delayed. Furthermore, patients may be quite symptomatic and suffer worsened quality of life. In this article, two of these conditions will be addressed; specifically, the atopic dermatitis-like and seborrheic dermatitis-like eruptions commonly seen in this patient population.
T
Atopic Dermatitis-Like Eruption Patients with HIV disease, either the full-blown acquired immunodeficiency syndrome (AIDS) or the AIDSrelated complex (ARC), may suffer from the same common inflammatory skin conditions seen in immunocompetent individuals. Because atopic dermatitis is quite a common affliction of the skin, it would be expected to occur in these patients at least as frequently as in normal subjects. As of this writing, there have been no reports that clearly indicate a marked increase in the frequency of atopic dermatitis and/or atopy in HIV-infected patients;
From the Departments ofpathology and Dermufology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas. Address correspondence to Clay J. Cockerell, MD, Division ofDermutopathology, The University of Texas Southwestern Medical Center, 5323 Hurry Hines Boulevard, Sprague Building, Dallas, TX 75235-9072.
0 2991 by Elsevier Science Publishing
Co., Inc.
l
0738-081x/91/$3.50
however, certain atopic dermatitis-like eruptions probably due to abnormal hypersensitivity responses have been demonstrated.1-5 Thus, there are two distinct groups: those with true atopic dermatitis and those with atopic dermatitis-like cutaneous eruptions. Atopic dermatitis is thought to be a manifestation of general hyperresponsiveness of the skin to external and internal stresses. Numerous theories have been evoked about the possible reason for the hyperresponsiveness, ranging from catecholamine and acetylcholine imbalance to abnormal circulating cytokines.6 In patients with HIV disease known to have had pre-existing atopic dermatitis, several different patterns have emerged. One is that of chronic stable atopic dermatitis without exacerbation seen throughout the course of the HIV disease.4 Other patients may develop severe flares of the atopic dermatitis, with progression to erythroderma (Plate 13).’ Response to removal of the precipitating factors such as low humidity and irritation and treatment with topical corticosteroids, creams, and ointments may be of poor efficacy in such cases. Patients are often extremely pruritic and may excoriate the skin extensively, resulting in open wounds that may serve as sites for external infection. Superinfection with herpes simplex virus resulting in Kaposi’s varicelliform eruption, a complication of atopic dermatitis also seen in immunocompetent hosts, may be quite severe in patients with HIV disease.s Furthermore, atopic patients are often chronic carriers of Staphylococcus [IUTCUS and may be at risk for the development of more serious staphylococcal pyoderma and bacteremia (Plate 14). Cultures should be performed to establish staphylococcal carriage and, when present, appropriate antimicrobials should be administered in an attempt to eradicate the carrier status. Application of topical antimicrobials, such as mupirocin, and the oral administration of rifampicin have both been shown to be of some benefit. In addition to exacerbation of atopic dermatitis, a number of patients with HIV disease may develop a dermati-
49
50
COCKERELL
Clinics in Dermatology
1991;9:49-52 tis, which is “atopic dermatitis-like” in nature.*,*,5 Widespread papulovesicular eruptions with scale and crust, accompanied by intense pruriitis and lichenification, may develop in the usual areas of predilection for atopic dermatitis but may also be generalized (Plate 15). There may be other unusual clinical manifestations such as marked hyperkeratosis and desquamation. The development of such unusual inflammatory dermatoses usually correlates with a T-helper cell count of less than 150 cells per mm3, as described by Kaplan.9 Just as with recalcitrant atopic dermatitis, these conditions may be quite refractory to therapy. Of interest, when histologic sections of such eruptions are examined, unusual patterns may be seen. Rather than the usual hyperplastic epidermis with spongiosis and lichenification characteristically seen with atopic dermatitis, patterns such as interface dermatitides with numerous dyskeratotic keratinocytes and granulomatous dermatitides have been noted.‘,1° Explanations for such findings are speculative but may include a manifestation of abnormal circulating cytokines or diminished Langerhans’ cell numbers. Although atopic dermatitis may occur in HIV-infected individuals, as it does in immunocompetent ones, it should be recognized that, when present, the manifestations may be unusual and more severe. In addition, widespread psoriasiform eruptions with features similar to atopic dermatitis may be found; such eruptions may in fact represent other diseases which, for lack of a better term, are often called atopic dermatitis.
Seborrheic
Dermatitis
A seborrheic dermatitis-like eruption is possibly one of the most common cutaneous manifestations of HIV disease.4 In some estimates, it is said to occur in incidences ranging from 32-83% of HIV-infected patients.” The reason for its development is unknown, but it has been postulated to be due to underlying stress, either physical or emotional, and/or overgrowth of Candida albic~ns~~ or Pityrosporum ovale13-15 secondary to the immunocompromise state. Although the seborrheic dermatitis-like condition of HIV infection has features similar to common seborrheic dermatitis, there are, in many cases, distinct differences. Seborrheic dermatitis in patients with HIV disease is characteristically more florid and may be characterized by intense erythema and thick scale distributed not only in the usual “seborrheic dermatitis” areas, but also in other locations16 (Plate 16). The scalp may be involved by thick, scaly, erythematous plaques, with accompanying oozing and weeping (Plate 17). Furthermore, there may be involvement of the intertriginous areas such as the axillae and groin (Plate 18). In some patients, widespread
eruptions may occur leading to diffuse erythroderma. Some cases may be associated with psoriasis, but in most, the characteristic seborrheic dermatitis-like nature of the eruption is maintained. Patients with HIV disease may develop this condition in association with pre-existing seborrheic dermatitis that simply becomes exacerbated, or they may develop it de novo with the onset of HIV disease or its sequelae. Furthermore, the greater the degree of immunodepression, ie, T-helper cell numbers less than 150 mm.3, the greater the tendency for the development of this condition, as well as its becoming more severe. Treatment is usually similar to that used in immunocompetent patients. Application of topical corticosteroid creams and ointments, as well as topical antifungal preparations, has been shown to be effective in some cases; however, in others, the condition is refractory to virtually any therapy. If treatment response is seen, following its discontinuation there may be prompt exacerbation. Scalp disease often requires keratolytic agents and selenium or tar shampoos with accompanying corticosteroid gels or solutions. Even in those cases, treatment response is variable to poor. In some cases, ultraviolet phototherapy may be beneficial. Although this seborrheic dermatitis-like condition may be a severe problem in patients with HIV disease, these individuals may also develop more classic seborrheic dermatitis, which poses little clinical problem and responds well to therapy. Histopathologically, there are some minor distinctions between the seborrheic dermatitis-like condition in HIVinfected individuals and seborrheic dermatitis in immunocompetent persons, l6 There is often a greater degree of parakeratosis, a more dense inflammatory cell infiltrate, and, interestingly, scattered individually necrotic keratinocytes throughout the epidermis. Furthermore, plasma cells may be seen in greater numbers in the HIV-infected.16 The overall pattern is very similar and in some cases identical to common seborrheic dermatitis.”
Conclusion Patients with HIV disease, be it AIDS or ARC, may develop a wide variety of unusual inflammatory dermatoses that may not correspond precisely to well-defined syndromes described in immunocompetent individuals. They may also develop the same eruptions seen in normal hosts, such as atopic dermatitis and seborrheic dermatitis, but these two usually well-defined, easily treated conditions may assume bizarre presentations and severe courses in the HIV-infected individual. It is essential to be aware of these eruptions as they may serve as the initial clue that an individual might be HIV infected.
Clinics in Dermatology 2991;9:49-51
SEBORRHEIC
Drug Names mupirocin: rifampicin:
Bactroban Rifadin, Rifamate,
COCKERELL ERUPTIONS
51
tions in the acquired immune deficiency syndrome: response to recombinant interferon gamma. Br Med J 1987;294:1185-86.
Rimactane
8. Penneys NS. Skin Manifestations of AIDS. Philadelphia, JB Lippincott, 1990, pp 80 - 85.
References 1, Cockerell
CJ, Rao BK. Histologic patterns of unusual inflammatory dermatoses in patients with human immunodeficiency virus infection. (Submitted for publication).
2. Penneys NP, Hicks B. Unusual cutaneous signs of acquired immunodeficiency syndrome. J Am Acad Dermatol 1985;13:845-52. 3. Cockerell CJ, Friedman-Kien AE. Skin manifestations HIV infection. Prim Care 1989;16:621.
AND ATOPIC DERMATITIS-LIKE
of
4 Goodman DS, Teplitz ED, Wishner A, et al. Prevalence of cutaneous disease in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. J Am Acad Dermatol 1987;17:210-20. 5. Kaplan MH, Sadick N, McNutt NS, et al. Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS). J Am Acad Dermatol1987;16:485-506. 6. Zung DYM, Rhodes AR, Geha RS. Atopic dermatitis. In Fitzpatrick TB, Eisen AZ, Wolff K, et al. (eds): Dermatology in General Medicine, 3rd Edition. New York, McGraw-Hill, 1987, pp 1385-1408. 7. Parkin JM, Eales LJ, Galazka AR, et al. Atopic manifesta-
9. Kaplan M. Combined HTLV-HIV infections. Presented at the American Society of Dermatopathology Meeting, Washington, DC, December, 1988. 10. Rico MJ, Cory WP, Gould EW, et al. Interface dermatitis in patients with the acquired immunodeficiency syndrome. J Am Acad Dermatol 1987;16:1209-17. 11. Mathes BM, Douglass MC. Seborrheic tients with acquired immunodeficiency Acad Dermatol 1985;13:947-51.
dermatitis in pasyndrome. J Am
12. Beare JM, Cheeseman EA, MacKenzie DWR. The association between Candida albicans and lesions of seborrheic eczema. Br J Dermatol 1968;80:675-81. 13. Faergemann J, Frederiksson T. Tinea versicolor with regard to seborrheic dermatitis. Arch Dermatol1979;115:966-68. 14. Leyden JJ, McGinley KJ, Kligrnan AM. Role of microorganisms in dandruff. Arch Dermatol 1976;112:333-38. 15. McGinley KJ, Leyden JJ, Marples RR, et al. Quantitative microbiology of the scalp in non-dandruff, dandruff and seborrheic dermatitis. J Invest Dermatol 1975;64:401-05. 16. Soeprono FF, Schinella RA, Cockerell CJ, et al. Seborrheiclike dermatitis of acquired immunodeficiency syndrome. J Am Acad Dermatol 1986;14:242-48.
