- Email: [email protected]
Cutaneous manifestations of early human immunodeficiency virus exposure
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Cutaneous manifestations of early human immunodeficiency virus exposure Robert S. Berger, MAJ, MC, USAF, Mary F. Stoner, CPT, MC, USAF, Edmund R. Hobbs, COL, MC, USAF, Thomas J. Hayes, MAJ, MC, USA.F,** and R. Neal Boswell, COL, MC, USAF* Lackland Air Force Base, TX After demonstrating antibodies to the human immunodeficiency virus (HIV), two hundred patients were interviewed and given a complete cutaneous and mucous membrane examination. By means of the Waiter Reed Staging Classification System for HIV infection, 155 patients were classified as having Walter Reed stage 1A-2A (WR1A-WR2A) infection. The prevalence of seborrheic dermatitis in this group was 36%. There were no other significant cutaneous findings in the WR1A-WR2A patient population. (J AM ACAD DERMATOL1988;19:298-303.)
The U.S. Air Force, under a Department of Defense directive, requires annual testing for human immunodeficiency virus (HIV) exposure in all active duty personnel. All those with positive test results for H I V antibodies are referred to Wilford Hall U.S. Air Force Medical Center for evaluation. We report the cutaneous findings of the first 200 consecutive H I V antibody-positive individuals examined at the medical center's dermatology department during the period February 1986 to March 1987. MATERIAL AND METHODS
To be considered positive for HIV exposure, the patient's initial blood sample had to react positively to the enzyme-linked immunosorbent assay and to a Western blot, with evidence of antibodies against the HIV envelope (GP41 or GP120) or against the envelope and core proteins (P24 or P55). Patients whose sera tested
From the Departments of Dermatology and Medicine,* Wilford Hall U.S. Air Force Medical Center, Lacldand Air Force Base, Texas. Accepted for publication Feb. 25, 1988. Reprint requests to: Dr. Robert S. Berger, Department of Dermatology/SGHMD, Wilford Hall USAF Medical Center, Lackland AFB TX 78236-5300. The opinions expressed herein represent those of the authors and do not necessarily represent those of the United States Air Force or the Department of Defense. **Now in private practice in Jacksonville, FL.
298
positive were referred to Wilford Hall USAF Medical Center for complete evaluation and staging of their infection according to the Walter Reed Staging Classification System/As part of that evaluation, all patients were seen in the dermatology department. All patients were questioned about skin disease histo13, and prior treatment. Information was sought regarding risk factors such as intravenous drug use, contact with prostitutes, homosexuality, bisexuality, and transfusions. Each patient then underwent a complete examination, including that of skin and mucous membranes. Cultures, biopsies, skin scrapings for potassium hydroxide, and Tzanck preparations were performed when appropriate. Biopsy specimens of all suspected lesions of oral hairy leukoplalda and Kaposi's sarcoma were taken for confirmation by histologie and/or electron microscopic criteria. The diagnosis of seborrheic dermatitis on physical examination was made when erythematous papules and plaques, some with a greasy yellow scale and others with a fine scale, were present in the glabella, eyebrows, paranasal area, periauricular area, scalp, and anterior aspect of the chest. A history of seborrheic dermatitis was considered positive only if a diagnosis had previously been made or if the clinical findings described above were present. Involvement of the groin or axilla alone was not considered as a positive finding by history or physical examination. Each patient's infection was staged for epidemiologic purposes according to the Walter Reed (WR) Staging Classification System (Table I). l This clinical elassifiea-
Volume 19 Number 2, Part 1 August 1988
Cutaneous manifestations of early H I V exposure 299
Table I. W a l t e r Reed ( W R ) staging classification of HIV infection Stage
HIV antibody and/or virus isolation
Chronic lymphadenopathy
Helper T celB/mm 3
WR0 WR1 WR2 WR3 WR4 WR5 WR6
+ + + + + +
+ +-+ --+
>400 >400 >400 <400 <400 <400 <400
I
Delayed
hypersensitivity
Thrush
I
OI
NL
-
NL NL
m _
NL
-
_ u -
P/C P/C
:l: •
+
01, Opportunistic infection; NL, normal; P, partial; P/C, partial/complete.
From Redfield R, Wright DG, Tramont EC. N Engl J Med 1986;314:131-2.
tion system classifies HIV infection according to a scale of 0 to 6. Each class is precisely defined by means of both physical findings and in vivo or in vitro immunologic assessment. The classification WR6 equates with acquired immunodeficiency syndrome (AIDS), as classifted by Centers for Disease Control (CDC) criteria. 2 The major factors determining the classification stage are as follows: HIV antibody positivity as serologically defined in this section, positive virus isolation, or both; lymphadenopathy for longer than 3 months; total number of helper T cells divided into greater than or less than 400 helper T cells (CD4-bearing peripheral blood mononuclear cells) per cubic millimeter; delayed hypersensitivity to subcutaneously injected antigens; anergy (with or without thrush); and opportunistic infections) The Walter Reed Classification System is applicable only to adults, because the absolute CD4 values and delayed hypersensitivity cutaneous responses are either not standardized or not reliable for newborn infants, children, and adolescents.I The suffix A denotes the absence of systemic symptoms, B denotes the presence of such symptoms, K denotes Kaposi's sarcoma, N denotes other malignancies, and CNS denotes neurologic disease. Orderly and inevitable progression from asymptomatie HIV seropositivity alone (WR1A) to AIDS (WR6) has not been substantiated unequivocally to date. All results were kept confidential, and patients were coded numerically. This 200-patient cohort group will be reevaluated at intervals of 12 months, or sooner if their medical condition indicates. RESULTS H I V infection in the majority of patients (155) was classified as W R 1 A or WR2A. In 45 patients, the classification was WR2B-WR6B. No infections were classified as WR1B, WR3B, or WR6A. Table II presents the Waiter Reed classifications
Table II. Walter Reed staging classification of patient population's H I V infection Patients Stage
No.
1A 1B 2A 2B 3A 3B 4A 4B 5A 5B 6A 6B
110 0 45 3 15 0 8 1 7 3 0 6
I
%
55.5 0.0 22.5 1.5 7.5 0.0 4.0 0.5 3.0 1.5 0.0 3.0
A, Asyrnptomatic (staging suffix); B, symptomatic (staging suffix).
for the study patient population. For two patients, HIV infection was considered unclassifiable according to the Waker Reed Staging Classification System because of the presence of anergy, but the patients had more than 400 total helper T cells/ram 3. Of the 200 patients, 193 were male. Ages ranged from 19 to 51 years, with the average being 28 years. Table III presents the cutaneous findings in the patient population. The most common cutaneous finding was seborrheic dermatitis in 34% of the cohort (68/200). Twelve additional patients (nine with stage W R 1 A or W R 2 A infection) had a history of seborrheic dermatitis but were in remission at the time of the study. These cases brought the total percentage of patients with seborrheic
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Table IlL Physical findings Findings
1
No. of patients
[ . ,.7iJ~ 2 A [l
68 52 13
40 34 5
7 8 3
1 0 0
7 4 0
5 0 2
1 1 0
2 2 1
2 2 2
29
12
8
0
5
3
1
0
0
10 5
0 0
2 3
1 0
1 1
I 0
0 0
2 0
0 0
Seborrheie dermatitis Tinea pedis Tinea corporis, tinea cruris Verrucae (not eondyloma) Thrush Molluscum GI Candida Oral hairy leukoplakia Kaposi's sarcoma
Stage
[ 2B" [ 3A" l 4A ]
4B [ 5A" } 5B I 613
2
0
0
0
0
0
0
0
0
2
0
0
0
1
0
0
1
0
2
1
0
0
0
0
0
0
0
3 1 0
A, A.symptomatic(stagingsuffix);B, symptomatic(stagingsuftLx);GI, gastrointestinal. Table IV. Sexually transmitted diseases
STDs,
Disease
Total No. of Infections
Gonorrhea Syphilis Condyloma Genital herpes Urethritis, nongonococcal Pedieulo.qis pubis Chancroid Scabies Multiple STDs (> 1)
104 39 38 12 12 1 1 1 38
]|
No. of patients
75 38 37 12 12 1 1 I 38
[ I
No. of patients with
54 3J 26 10 8 I 1 1 26
Sexuallytransmitted diseases.
dermatitis to 40% (80/200). Seborrheic dermatitis was found in 30.3% (47/155) of patients with stage W R 1 A or W R 2 A infection. The addition of the historical positives brought the total prevalence of seborrheic dermatitis in patients with stage WR1A-2A infection to 36% (56/155). Of 10 patients with thrush, eight had their HIV infection staged greater than WR2A. Two patients had oral hairy leukoplakia (WR3A, WR5A). Only two patients had Kaposi's sarcoma; in one patient, infection was classified as stage WR1AK, and in the other, stage WR6BK. A history of sexually transmitted disease (Table IV) was elicited in 131 patients (65.5%). Diseases included gonorrhea, syphilis, condyloma acuminaturn, genital herpes, n o n g o n ~ l urethritis, lymphogranuloma venereum, chancroid, pediculosis
pubis, and scabies. The total number of infections in these 131 patients was 208. The most common infection was gonorrhea, with 104 cases in 75 patients. Sixteen patients accounted for 45 gonorrheal infections, with three patients having been infected eight times with gonococci. In 54 patients (72%) with gonorrhea, HIV infection was classified as stage W R I A or WR2A. The second most common sexually transmitted disease was syphilis, with 39 cases. One patient was reportedly infected five times. Of the 39 patients with syphilis, 33 (87%) were considered to have stage WR1A or WR2A infection. Condyloma acuminatum was present in 38 patients (19%). Of the 38 patients, 26 (68%) had stage W R I A or WR2A infection. There were 12 eases each of genital herpes, nonspecific urethritis, or both. Thirty-eight patients had multiple sexually
Volume 19 Number 2, Part 1 August 1988
transmitted diseases. Of these, 26 (68%) were classified as having stage WR1A or WR2A HIV infection. Table V presents risk factor data obtained from our patient cohort. Twenty-nine patients (14.5%) related a history of infection with hepatitis, primarily type B. Four patients were health care personnel who claimed exposure to HIV-infected patients but had no documented exposure to body fluids or needles. One patient (not on active duty) admitted to intravenous drug abuse, and one patient (on active duty) was married to an addict. An additional male patient admitted to being a prostitute.
Cutaneous manifestations of early HIV exposure 301
Table V. Historical findings
No. of
No. in stage
Risk factor
l
patients
Prostitute sex partner(s) Hepatitis Homosexual HIV + partner Herpes zoster Transfusion Laboratory accident Former prostitute African partner IV drug abuse IV drug abuse partner
39 28 16 11 8 4 4 1 1 1 1
29 21 13 8 4 3 4 1 1 1 1
DISCUSSION The dermatologic findings of patients with AIDS or AIDS-related complex are well known. 3"9There are scant data available regarding cutaneous manifestations of asymptomatic or lymphadenopathie syndrome HIV-infected patients. Recent articles deal primarily with patients with AIDS or AIDSrelated complex when describing cutaneous findings. 6-~6The infections of the patients included in these studies were classified by the CDC definition of AIDS and AIDS-related compiex. Of these articles, only two 9,16mention HIV-infected or exposed individuals whose conditions were not classified as AIDS or AIDS-related complex in their patient population. The lack of significant physical findings was not unexpected, because most of our patients were asymptomatic or had lymphadenopathy alone, confirming the observations of a previous study. 9 The high incidence of seborrheic dermatitis in our patient cohort also confirms the findings of a recent study that included a small number of non-AIDS patients with HIV antibody seropositivity)6 A 36% incidence is much higher than that in the general population: 8% in 19-year-old recruits,* 1% to 3% in the general population, ~7 3% to 5% in young adults, ~7 and less than 5% among patients without AIDS who were seen on a consultation basis by a dermatologist: Recent sttidies comparing HIV antibody-seropositive homosexual or bisexual men with HIV antibody-seronegative homosexual or bisexual men found a 3% and a 19% incidence of seborrheic dermatitis in HIV antibody-negative
patients, respectively. 9,16 In the first study, 10% of the HIV antibody-seropositive patients demonstrated seborrheic dermatitis: This study did not include criteria defining physical findings of seborrheic dermatitis, however. Thus the incidence of seborrheic dermatitis may be higher or lower, depending on their inclusion criteria. The latter study demonstrated a 33.3% incidence of seborrheic dermatitis in antibody-seropositive patients and AIDS patients, t6 We included those patients who gave a verified history of seborrheic dermatitis but were in remission at the time of examination. Because the majority of patients in our study had a relatively intact immune system at the time of examination, response to treatment would be expected. Our data seem to corroborate the observation that seborrheic dermatitis is a cutaneous marker for HIV infection:. 7.12In addition, our data seem to suggest that seborrheic dermatitis is seen with increased frequency in individuals who do not yet demonstrate symptoms of HIV infection. Although the presence of seborrheic dermatitis in patients with AIDS or AIDS-related complex thought to be a poor prognostic sign: the prognostic significance of seborrheic dermatitis in early HIV exposure is unknown. The incidence of other cutaneous findings was similar to published data of normal population groups.*,~7 It is not surprising to find a normal incidence of dermatologic conditions such as dermatophyte infections, verrucae, and moUuscum in
*Garcia RL. Skin disorders in air force recruits. J Assoe Mil Derm 1976(Summer);2(1):61.
*Garcia RL. Skin disorders ha air force recruits. J Assoe Mil Derm 1976(Stmarner);2(1):61,
302
Journal of the American Academyof Dermatology
Berger et aL
the patients in the lower Walter Reed stages. The low incidence of Kaposi's sarcoma and oral hairy leukoplakia was also expected. A recent study found an increase in oral hairy leukoplakia in non-AIDS H I V antibody-seropositive patients. ~6It is not known whether these diagnoses of oral hairy leukoplakia were confirmed by histologic or electron microscopic criteria. Several clinically suspicious lesions were not confirmed by histologic and electron microscopic criteria in our patient population. Although we present the results of our interviews with respect to risk factors, we question the reliability of the negative responses, especially those concerning homosexuality. There is a potentially negative impact on active duty personnel who admit to homosexuality or to drug abuse. Relating a history of exposure to prostitutes is a "safe" way to document H I V exposure in the military setting. We thus regard such a history with suspicion. The U.S. Air Force requirement for random urine drug screening validates the number of negative drug abuse responses. None of the patients presented in this report had records of a prior positive urine test result. Studies involving risk factors for HIV exposure in military personnet probably are not reliable unless the patient directly admits to risk factors, is The history of sexually transmitted diseases obtained from these patients was generally corroborated by the patients' records and by the patients' listing of specific dates of infection and treatment. The latter information was often recorded by several different health care providers. Sexual promiscuity, as seen in this patient population, is certain to increase the risk of HIV exposure. Our patients' HIVinfections were divided into two broad categories: WR1A-2A and WR2B-6B. Patients with WR1A-2A infection have none of the classic markers for AIDS progression: low CD4 absolute numbers, thrombocytopenia, thrush, oral hairy leukoplakia, and systemic symptoms. Patients with infections initially staged as WR2B or greater all have one or more of the disease progression markers. Ninety-nine percent of our patients had HIV infection classifiable by means of the Walter Reed Staging Classification System. This ability to classify HIV infection in almost all seropositive patients is essential in longitudinal long-term studies.
Since the mandatory testing of Air Force personnel began in the early part of 1986, many of the early patients seen at Wilford Hall were referred by physicians or were self-referred because of symptoms. This factor is important because our early patients tend to be in more advanced stages, to have more symptoms, or both, than those identified by simple screening. For example, in the first 45 patients, 17 (37.7%) had stage WR2B infection or higher, with five (11.1%) having stage WR6B infection. In the next 155 patients, only 24 (15.5%) had stage WR2B infection or higher; only one (0.79%) had stage WR6B. These latter figures probably reflect the more rapid identification of personnel with a recent exposure. CONCLUSION We have presented the histories and the dermatologic examination findings on 200 patients infected with HIV. A markedly increased incidence of seborrheic dermatitis in patients with HIV infection was confirmed in patients whose infection was classified as stage WR1A-2A. The remainder of the cutaneous examination findings in HIV-infected individuals with stage WR 1A-2A infection does not differ from that of the normal population. Whether there is a prognostic association with seborrheic dermatitis in these individuals requires additional study. REFERENCES
1. RedfieldR., Wright DG, Tramont EC. The Walter Reed staging classification for HTLV-III/LAV infection. N Engl 3 Med 1986;314:131-2. 2. Leadsfromthe MMWR: revisionof the CDC surveillance case definitionof acquired immunodeficiencysyndrome. JAMA 1987;258:1143-54. 3. GottliebMS, SchroffR, SchankerHM, etal.Pneumocystis carinii pneumoniaand mucosalcandidiasisin previously healthy homosexualmen. N Engl J Med 1981;305:142531. 4. Kaplan MH, Sadick N, McNutt NS, Meltzer M, Sarngadharan MG, Pahwa S. Dermatologic findings and manifestations of acquired immunodeficienoysyndrome (AIDS). J AM ACADDER.MATOL1987;16:485-506. 5. RanpenFHJ. AIDS and thedermatologist.Int J Dermatol 1987;26(1):1-7. 6. Mathes BM, Douglass MC. Seborrheic dermatitis in patients with acquiredimmunodefieiencysyndrome.J AM A c ~ DER~ATOL1985;13:947-51. 7. Eisenstat BA, Wormser GP. Seborrheic dermatitis and butterfly rash in AIDS [Letter]. N Engl J Meal 1984;311:189. 8. Gretzula J, Penneys NS. Complexviral and fungal skin lesions of patients with acquired immunodeficiencysyndrome. J AM ACAODERr~TOL1987;16:1151-4.
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Cutaneous manifestations of early HIV exposure
9. Sindrup JI-/, Lisby G, Weismarm K, Wantzin GL. Skin manifestations in AIDS, HIV infection,and AIDS-related complex. Int J Dermatol 1987;26:267-72. 10. Shapiro RS, Samorodin C, Hood AF. Pruritis as a presenting sign of acquired immunodeficiencysyndrome.J AM ACADDERMATOL1987;16:1115-7. 11. Soeprono FF, Schinella RA. Eosinophilicpustular folliculitis in patients with acquired immunodeficiencysyndrome. J AM ACADDERMATOL1986;14:1020-2. 12. Soeprono FF, Schinella RA, Cockerell CJ, Comite SL. Seborrheic-likedermatitis of acquired immunodeficiency syndrome. J AM ACADDEgM^TOL1986;14:242-8. 13. Friedman-Kien AE, Lafleur FL, Gendler E, et al. Herpes zoster: a possible early clinical sign for development of acquired immunodeficiencysyndrome in high-riskindividuals. J AM ACAt~DERMATOL1986;14:1023-8. 14. Chernosky ME, Finley VK. Yellow nail syndrome in
!
15. 16.
17.
18.
patients with acquired immunodeficiency disease. J AM Acho DERMATOL1985;13:731-6. PenneysNS, Hicks B. Unusual cutaneous lesionsassociated with acquired immunodeficiency syndrome. J AM ACAD Deg~,fa'roL 1985;13:845-52. Mat.isWL, Triana A, Shapiro R, Eldred L, Polk BF, Hood AF. Dermatologic findings associated with human immunodefieiency virus infection. J AM ACAU DEaMA'rOL 1987;17:746-51. Johnson M-LT, Roberts J. Prevalence of dermatological diseases among persons 1-74 years of age: United States. Publication No. (PHS)79-1660. Washington, DC: U.S. Department of Health and Human Services, 1977. Potterat J J, Phillips L, Muth JB. Lying to military physicians about risk factors for HIV infections. JAMA 1987;257:1727.
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I
Pemphigoid and ulcerative colitis J. F. S. J.
H. Barth, M . B . , M . R . C . P . , * S. E. Kelly, M.B., M . R . C . P . , * Wojnarowska, B.Sc., B.M., M.R.C.P.,* J. A. Savin, M . D . , F . R . C . P . , * * Whittaker, M.B., M . R . C . P . , * * * J. J. Cream, M . D . , F . R . C . P . , * * * * and E. White, M.D., F.R.C.P.***** Oxford, Edinburgh, Middlesex, London,
and
Southampton, United Kingdom We report eight patients with ulcerative colitis who have subsequently developed pemphigoid. Four patients were investigated to determine the pattern of pemphigoid antibody staining on whole and chemically split skin and oral mucosa to distinguish between pemphigoid and epidermolysis bullosa acquisita. The findings were suggestive of pemphigoid with a predominantly epidermal pattern. Three patients were studied for the presence of antibodies against the colon (which were absent). The relationship between pemphigoid and ulcerative colitis is discussed in relation to a case-control study. (J AM ACAD DEaMATOL1988;19:303-8.)
Bullous pemphigoid and ulcerative colitis may both be associated with other autoimmune diseases. Bullous pemphigoid is an autoimmune disease with autoantibodies directed against the base-
From the Departmentsof Dermatology,SladeHospital,Oxford*;The Royal Infirmary,Edinburgh**,EalingHospital,Southall,Middlesex***; Charing Cross Hospital, London****;and Royal South Hants Hospital, Southampton.***** Accepted for publicationNov. 30, 1987. Reprint requests to: Dr. J. H. Barth, Departmentof Dermatology, The Slade Hospital, Headington. Oxford OX3 7JH, United Kingdom.
ment membrane zone. Although a small number of patients with ulcerative cdlitis have antibodies related to the colon, autoimmunity is not thought to be its main pathogenic mechanism.~'3 There have been seven reports of patients with both diseases, but the connection has never been stressed. 49 We have seen eight additional patients and describe five in detail. In addition, we have examined their sera for the presence o f anticolon antibodies by immunoperoxidase techniques, and tested for circulating a n t i - b a s e m e n t membrane zone antibodies by indirect immunofluorescence techniques. 303
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Cutaneous manifestations of early human immunodeficiency virus exposure Robert S. Berger, MAJ, MC, USAF, Mary F. Stoner, CPT, MC, USAF, Edmund R. Hobbs, COL, MC, USAF, Thomas J. Hayes, MAJ, MC, USA.F,** and R. Neal Boswell, COL, MC, USAF* Lackland Air Force Base, TX After demonstrating antibodies to the human immunodeficiency virus (HIV), two hundred patients were interviewed and given a complete cutaneous and mucous membrane examination. By means of the Waiter Reed Staging Classification System for HIV infection, 155 patients were classified as having Walter Reed stage 1A-2A (WR1A-WR2A) infection. The prevalence of seborrheic dermatitis in this group was 36%. There were no other significant cutaneous findings in the WR1A-WR2A patient population. (J AM ACAD DERMATOL1988;19:298-303.)
The U.S. Air Force, under a Department of Defense directive, requires annual testing for human immunodeficiency virus (HIV) exposure in all active duty personnel. All those with positive test results for H I V antibodies are referred to Wilford Hall U.S. Air Force Medical Center for evaluation. We report the cutaneous findings of the first 200 consecutive H I V antibody-positive individuals examined at the medical center's dermatology department during the period February 1986 to March 1987. MATERIAL AND METHODS
To be considered positive for HIV exposure, the patient's initial blood sample had to react positively to the enzyme-linked immunosorbent assay and to a Western blot, with evidence of antibodies against the HIV envelope (GP41 or GP120) or against the envelope and core proteins (P24 or P55). Patients whose sera tested
From the Departments of Dermatology and Medicine,* Wilford Hall U.S. Air Force Medical Center, Lacldand Air Force Base, Texas. Accepted for publication Feb. 25, 1988. Reprint requests to: Dr. Robert S. Berger, Department of Dermatology/SGHMD, Wilford Hall USAF Medical Center, Lackland AFB TX 78236-5300. The opinions expressed herein represent those of the authors and do not necessarily represent those of the United States Air Force or the Department of Defense. **Now in private practice in Jacksonville, FL.
298
positive were referred to Wilford Hall USAF Medical Center for complete evaluation and staging of their infection according to the Walter Reed Staging Classification System/As part of that evaluation, all patients were seen in the dermatology department. All patients were questioned about skin disease histo13, and prior treatment. Information was sought regarding risk factors such as intravenous drug use, contact with prostitutes, homosexuality, bisexuality, and transfusions. Each patient then underwent a complete examination, including that of skin and mucous membranes. Cultures, biopsies, skin scrapings for potassium hydroxide, and Tzanck preparations were performed when appropriate. Biopsy specimens of all suspected lesions of oral hairy leukoplalda and Kaposi's sarcoma were taken for confirmation by histologie and/or electron microscopic criteria. The diagnosis of seborrheic dermatitis on physical examination was made when erythematous papules and plaques, some with a greasy yellow scale and others with a fine scale, were present in the glabella, eyebrows, paranasal area, periauricular area, scalp, and anterior aspect of the chest. A history of seborrheic dermatitis was considered positive only if a diagnosis had previously been made or if the clinical findings described above were present. Involvement of the groin or axilla alone was not considered as a positive finding by history or physical examination. Each patient's infection was staged for epidemiologic purposes according to the Walter Reed (WR) Staging Classification System (Table I). l This clinical elassifiea-
Volume 19 Number 2, Part 1 August 1988
Cutaneous manifestations of early H I V exposure 299
Table I. W a l t e r Reed ( W R ) staging classification of HIV infection Stage
HIV antibody and/or virus isolation
Chronic lymphadenopathy
Helper T celB/mm 3
WR0 WR1 WR2 WR3 WR4 WR5 WR6
+ + + + + +
+ +-+ --+
>400 >400 >400 <400 <400 <400 <400
I
Delayed
hypersensitivity
Thrush
I
OI
NL
-
NL NL
m _
NL
-
_ u -
P/C P/C
:l: •
+
01, Opportunistic infection; NL, normal; P, partial; P/C, partial/complete.
From Redfield R, Wright DG, Tramont EC. N Engl J Med 1986;314:131-2.
tion system classifies HIV infection according to a scale of 0 to 6. Each class is precisely defined by means of both physical findings and in vivo or in vitro immunologic assessment. The classification WR6 equates with acquired immunodeficiency syndrome (AIDS), as classifted by Centers for Disease Control (CDC) criteria. 2 The major factors determining the classification stage are as follows: HIV antibody positivity as serologically defined in this section, positive virus isolation, or both; lymphadenopathy for longer than 3 months; total number of helper T cells divided into greater than or less than 400 helper T cells (CD4-bearing peripheral blood mononuclear cells) per cubic millimeter; delayed hypersensitivity to subcutaneously injected antigens; anergy (with or without thrush); and opportunistic infections) The Walter Reed Classification System is applicable only to adults, because the absolute CD4 values and delayed hypersensitivity cutaneous responses are either not standardized or not reliable for newborn infants, children, and adolescents.I The suffix A denotes the absence of systemic symptoms, B denotes the presence of such symptoms, K denotes Kaposi's sarcoma, N denotes other malignancies, and CNS denotes neurologic disease. Orderly and inevitable progression from asymptomatie HIV seropositivity alone (WR1A) to AIDS (WR6) has not been substantiated unequivocally to date. All results were kept confidential, and patients were coded numerically. This 200-patient cohort group will be reevaluated at intervals of 12 months, or sooner if their medical condition indicates. RESULTS H I V infection in the majority of patients (155) was classified as W R 1 A or WR2A. In 45 patients, the classification was WR2B-WR6B. No infections were classified as WR1B, WR3B, or WR6A. Table II presents the Waiter Reed classifications
Table II. Walter Reed staging classification of patient population's H I V infection Patients Stage
No.
1A 1B 2A 2B 3A 3B 4A 4B 5A 5B 6A 6B
110 0 45 3 15 0 8 1 7 3 0 6
I
%
55.5 0.0 22.5 1.5 7.5 0.0 4.0 0.5 3.0 1.5 0.0 3.0
A, Asyrnptomatic (staging suffix); B, symptomatic (staging suffix).
for the study patient population. For two patients, HIV infection was considered unclassifiable according to the Waker Reed Staging Classification System because of the presence of anergy, but the patients had more than 400 total helper T cells/ram 3. Of the 200 patients, 193 were male. Ages ranged from 19 to 51 years, with the average being 28 years. Table III presents the cutaneous findings in the patient population. The most common cutaneous finding was seborrheic dermatitis in 34% of the cohort (68/200). Twelve additional patients (nine with stage W R 1 A or W R 2 A infection) had a history of seborrheic dermatitis but were in remission at the time of the study. These cases brought the total percentage of patients with seborrheic
Journal of the
300
American Academy of Dermatology
Berger et al.
Table IlL Physical findings Findings
1
No. of patients
[ . ,.7iJ~ 2 A [l
68 52 13
40 34 5
7 8 3
1 0 0
7 4 0
5 0 2
1 1 0
2 2 1
2 2 2
29
12
8
0
5
3
1
0
0
10 5
0 0
2 3
1 0
1 1
I 0
0 0
2 0
0 0
Seborrheie dermatitis Tinea pedis Tinea corporis, tinea cruris Verrucae (not eondyloma) Thrush Molluscum GI Candida Oral hairy leukoplakia Kaposi's sarcoma
Stage
[ 2B" [ 3A" l 4A ]
4B [ 5A" } 5B I 613
2
0
0
0
0
0
0
0
0
2
0
0
0
1
0
0
1
0
2
1
0
0
0
0
0
0
0
3 1 0
A, A.symptomatic(stagingsuffix);B, symptomatic(stagingsuftLx);GI, gastrointestinal. Table IV. Sexually transmitted diseases
STDs,
Disease
Total No. of Infections
Gonorrhea Syphilis Condyloma Genital herpes Urethritis, nongonococcal Pedieulo.qis pubis Chancroid Scabies Multiple STDs (> 1)
104 39 38 12 12 1 1 1 38
]|
No. of patients
75 38 37 12 12 1 1 I 38
[ I
No. of patients with
54 3J 26 10 8 I 1 1 26
Sexuallytransmitted diseases.
dermatitis to 40% (80/200). Seborrheic dermatitis was found in 30.3% (47/155) of patients with stage W R 1 A or W R 2 A infection. The addition of the historical positives brought the total prevalence of seborrheic dermatitis in patients with stage WR1A-2A infection to 36% (56/155). Of 10 patients with thrush, eight had their HIV infection staged greater than WR2A. Two patients had oral hairy leukoplakia (WR3A, WR5A). Only two patients had Kaposi's sarcoma; in one patient, infection was classified as stage WR1AK, and in the other, stage WR6BK. A history of sexually transmitted disease (Table IV) was elicited in 131 patients (65.5%). Diseases included gonorrhea, syphilis, condyloma acuminaturn, genital herpes, n o n g o n ~ l urethritis, lymphogranuloma venereum, chancroid, pediculosis
pubis, and scabies. The total number of infections in these 131 patients was 208. The most common infection was gonorrhea, with 104 cases in 75 patients. Sixteen patients accounted for 45 gonorrheal infections, with three patients having been infected eight times with gonococci. In 54 patients (72%) with gonorrhea, HIV infection was classified as stage W R I A or WR2A. The second most common sexually transmitted disease was syphilis, with 39 cases. One patient was reportedly infected five times. Of the 39 patients with syphilis, 33 (87%) were considered to have stage WR1A or WR2A infection. Condyloma acuminatum was present in 38 patients (19%). Of the 38 patients, 26 (68%) had stage W R I A or WR2A infection. There were 12 eases each of genital herpes, nonspecific urethritis, or both. Thirty-eight patients had multiple sexually
Volume 19 Number 2, Part 1 August 1988
transmitted diseases. Of these, 26 (68%) were classified as having stage WR1A or WR2A HIV infection. Table V presents risk factor data obtained from our patient cohort. Twenty-nine patients (14.5%) related a history of infection with hepatitis, primarily type B. Four patients were health care personnel who claimed exposure to HIV-infected patients but had no documented exposure to body fluids or needles. One patient (not on active duty) admitted to intravenous drug abuse, and one patient (on active duty) was married to an addict. An additional male patient admitted to being a prostitute.
Cutaneous manifestations of early HIV exposure 301
Table V. Historical findings
No. of
No. in stage
Risk factor
l
patients
Prostitute sex partner(s) Hepatitis Homosexual HIV + partner Herpes zoster Transfusion Laboratory accident Former prostitute African partner IV drug abuse IV drug abuse partner
39 28 16 11 8 4 4 1 1 1 1
29 21 13 8 4 3 4 1 1 1 1
DISCUSSION The dermatologic findings of patients with AIDS or AIDS-related complex are well known. 3"9There are scant data available regarding cutaneous manifestations of asymptomatic or lymphadenopathie syndrome HIV-infected patients. Recent articles deal primarily with patients with AIDS or AIDSrelated complex when describing cutaneous findings. 6-~6The infections of the patients included in these studies were classified by the CDC definition of AIDS and AIDS-related compiex. Of these articles, only two 9,16mention HIV-infected or exposed individuals whose conditions were not classified as AIDS or AIDS-related complex in their patient population. The lack of significant physical findings was not unexpected, because most of our patients were asymptomatic or had lymphadenopathy alone, confirming the observations of a previous study. 9 The high incidence of seborrheic dermatitis in our patient cohort also confirms the findings of a recent study that included a small number of non-AIDS patients with HIV antibody seropositivity)6 A 36% incidence is much higher than that in the general population: 8% in 19-year-old recruits,* 1% to 3% in the general population, ~7 3% to 5% in young adults, ~7 and less than 5% among patients without AIDS who were seen on a consultation basis by a dermatologist: Recent sttidies comparing HIV antibody-seropositive homosexual or bisexual men with HIV antibody-seronegative homosexual or bisexual men found a 3% and a 19% incidence of seborrheic dermatitis in HIV antibody-negative
patients, respectively. 9,16 In the first study, 10% of the HIV antibody-seropositive patients demonstrated seborrheic dermatitis: This study did not include criteria defining physical findings of seborrheic dermatitis, however. Thus the incidence of seborrheic dermatitis may be higher or lower, depending on their inclusion criteria. The latter study demonstrated a 33.3% incidence of seborrheic dermatitis in antibody-seropositive patients and AIDS patients, t6 We included those patients who gave a verified history of seborrheic dermatitis but were in remission at the time of examination. Because the majority of patients in our study had a relatively intact immune system at the time of examination, response to treatment would be expected. Our data seem to corroborate the observation that seborrheic dermatitis is a cutaneous marker for HIV infection:. 7.12In addition, our data seem to suggest that seborrheic dermatitis is seen with increased frequency in individuals who do not yet demonstrate symptoms of HIV infection. Although the presence of seborrheic dermatitis in patients with AIDS or AIDS-related complex thought to be a poor prognostic sign: the prognostic significance of seborrheic dermatitis in early HIV exposure is unknown. The incidence of other cutaneous findings was similar to published data of normal population groups.*,~7 It is not surprising to find a normal incidence of dermatologic conditions such as dermatophyte infections, verrucae, and moUuscum in
*Garcia RL. Skin disorders in air force recruits. J Assoe Mil Derm 1976(Summer);2(1):61.
*Garcia RL. Skin disorders ha air force recruits. J Assoe Mil Derm 1976(Stmarner);2(1):61,
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Berger et aL
the patients in the lower Walter Reed stages. The low incidence of Kaposi's sarcoma and oral hairy leukoplakia was also expected. A recent study found an increase in oral hairy leukoplakia in non-AIDS H I V antibody-seropositive patients. ~6It is not known whether these diagnoses of oral hairy leukoplakia were confirmed by histologic or electron microscopic criteria. Several clinically suspicious lesions were not confirmed by histologic and electron microscopic criteria in our patient population. Although we present the results of our interviews with respect to risk factors, we question the reliability of the negative responses, especially those concerning homosexuality. There is a potentially negative impact on active duty personnel who admit to homosexuality or to drug abuse. Relating a history of exposure to prostitutes is a "safe" way to document H I V exposure in the military setting. We thus regard such a history with suspicion. The U.S. Air Force requirement for random urine drug screening validates the number of negative drug abuse responses. None of the patients presented in this report had records of a prior positive urine test result. Studies involving risk factors for HIV exposure in military personnet probably are not reliable unless the patient directly admits to risk factors, is The history of sexually transmitted diseases obtained from these patients was generally corroborated by the patients' records and by the patients' listing of specific dates of infection and treatment. The latter information was often recorded by several different health care providers. Sexual promiscuity, as seen in this patient population, is certain to increase the risk of HIV exposure. Our patients' HIVinfections were divided into two broad categories: WR1A-2A and WR2B-6B. Patients with WR1A-2A infection have none of the classic markers for AIDS progression: low CD4 absolute numbers, thrombocytopenia, thrush, oral hairy leukoplakia, and systemic symptoms. Patients with infections initially staged as WR2B or greater all have one or more of the disease progression markers. Ninety-nine percent of our patients had HIV infection classifiable by means of the Walter Reed Staging Classification System. This ability to classify HIV infection in almost all seropositive patients is essential in longitudinal long-term studies.
Since the mandatory testing of Air Force personnel began in the early part of 1986, many of the early patients seen at Wilford Hall were referred by physicians or were self-referred because of symptoms. This factor is important because our early patients tend to be in more advanced stages, to have more symptoms, or both, than those identified by simple screening. For example, in the first 45 patients, 17 (37.7%) had stage WR2B infection or higher, with five (11.1%) having stage WR6B infection. In the next 155 patients, only 24 (15.5%) had stage WR2B infection or higher; only one (0.79%) had stage WR6B. These latter figures probably reflect the more rapid identification of personnel with a recent exposure. CONCLUSION We have presented the histories and the dermatologic examination findings on 200 patients infected with HIV. A markedly increased incidence of seborrheic dermatitis in patients with HIV infection was confirmed in patients whose infection was classified as stage WR1A-2A. The remainder of the cutaneous examination findings in HIV-infected individuals with stage WR 1A-2A infection does not differ from that of the normal population. Whether there is a prognostic association with seborrheic dermatitis in these individuals requires additional study. REFERENCES
1. RedfieldR., Wright DG, Tramont EC. The Walter Reed staging classification for HTLV-III/LAV infection. N Engl 3 Med 1986;314:131-2. 2. Leadsfromthe MMWR: revisionof the CDC surveillance case definitionof acquired immunodeficiencysyndrome. JAMA 1987;258:1143-54. 3. GottliebMS, SchroffR, SchankerHM, etal.Pneumocystis carinii pneumoniaand mucosalcandidiasisin previously healthy homosexualmen. N Engl J Med 1981;305:142531. 4. Kaplan MH, Sadick N, McNutt NS, Meltzer M, Sarngadharan MG, Pahwa S. Dermatologic findings and manifestations of acquired immunodeficienoysyndrome (AIDS). J AM ACADDER.MATOL1987;16:485-506. 5. RanpenFHJ. AIDS and thedermatologist.Int J Dermatol 1987;26(1):1-7. 6. Mathes BM, Douglass MC. Seborrheic dermatitis in patients with acquiredimmunodefieiencysyndrome.J AM A c ~ DER~ATOL1985;13:947-51. 7. Eisenstat BA, Wormser GP. Seborrheic dermatitis and butterfly rash in AIDS [Letter]. N Engl J Meal 1984;311:189. 8. Gretzula J, Penneys NS. Complexviral and fungal skin lesions of patients with acquired immunodeficiencysyndrome. J AM ACAODERr~TOL1987;16:1151-4.
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Cutaneous manifestations of early HIV exposure
9. Sindrup JI-/, Lisby G, Weismarm K, Wantzin GL. Skin manifestations in AIDS, HIV infection,and AIDS-related complex. Int J Dermatol 1987;26:267-72. 10. Shapiro RS, Samorodin C, Hood AF. Pruritis as a presenting sign of acquired immunodeficiencysyndrome.J AM ACADDERMATOL1987;16:1115-7. 11. Soeprono FF, Schinella RA. Eosinophilicpustular folliculitis in patients with acquired immunodeficiencysyndrome. J AM ACADDERMATOL1986;14:1020-2. 12. Soeprono FF, Schinella RA, Cockerell CJ, Comite SL. Seborrheic-likedermatitis of acquired immunodeficiency syndrome. J AM ACADDEgM^TOL1986;14:242-8. 13. Friedman-Kien AE, Lafleur FL, Gendler E, et al. Herpes zoster: a possible early clinical sign for development of acquired immunodeficiencysyndrome in high-riskindividuals. J AM ACAt~DERMATOL1986;14:1023-8. 14. Chernosky ME, Finley VK. Yellow nail syndrome in
!
15. 16.
17.
18.
patients with acquired immunodeficiency disease. J AM Acho DERMATOL1985;13:731-6. PenneysNS, Hicks B. Unusual cutaneous lesionsassociated with acquired immunodeficiency syndrome. J AM ACAD Deg~,fa'roL 1985;13:845-52. Mat.isWL, Triana A, Shapiro R, Eldred L, Polk BF, Hood AF. Dermatologic findings associated with human immunodefieiency virus infection. J AM ACAU DEaMA'rOL 1987;17:746-51. Johnson M-LT, Roberts J. Prevalence of dermatological diseases among persons 1-74 years of age: United States. Publication No. (PHS)79-1660. Washington, DC: U.S. Department of Health and Human Services, 1977. Potterat J J, Phillips L, Muth JB. Lying to military physicians about risk factors for HIV infections. JAMA 1987;257:1727.
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Pemphigoid and ulcerative colitis J. F. S. J.
H. Barth, M . B . , M . R . C . P . , * S. E. Kelly, M.B., M . R . C . P . , * Wojnarowska, B.Sc., B.M., M.R.C.P.,* J. A. Savin, M . D . , F . R . C . P . , * * Whittaker, M.B., M . R . C . P . , * * * J. J. Cream, M . D . , F . R . C . P . , * * * * and E. White, M.D., F.R.C.P.***** Oxford, Edinburgh, Middlesex, London,
and
Southampton, United Kingdom We report eight patients with ulcerative colitis who have subsequently developed pemphigoid. Four patients were investigated to determine the pattern of pemphigoid antibody staining on whole and chemically split skin and oral mucosa to distinguish between pemphigoid and epidermolysis bullosa acquisita. The findings were suggestive of pemphigoid with a predominantly epidermal pattern. Three patients were studied for the presence of antibodies against the colon (which were absent). The relationship between pemphigoid and ulcerative colitis is discussed in relation to a case-control study. (J AM ACAD DEaMATOL1988;19:303-8.)
Bullous pemphigoid and ulcerative colitis may both be associated with other autoimmune diseases. Bullous pemphigoid is an autoimmune disease with autoantibodies directed against the base-
From the Departmentsof Dermatology,SladeHospital,Oxford*;The Royal Infirmary,Edinburgh**,EalingHospital,Southall,Middlesex***; Charing Cross Hospital, London****;and Royal South Hants Hospital, Southampton.***** Accepted for publicationNov. 30, 1987. Reprint requests to: Dr. J. H. Barth, Departmentof Dermatology, The Slade Hospital, Headington. Oxford OX3 7JH, United Kingdom.
ment membrane zone. Although a small number of patients with ulcerative cdlitis have antibodies related to the colon, autoimmunity is not thought to be its main pathogenic mechanism.~'3 There have been seven reports of patients with both diseases, but the connection has never been stressed. 49 We have seen eight additional patients and describe five in detail. In addition, we have examined their sera for the presence o f anticolon antibodies by immunoperoxidase techniques, and tested for circulating a n t i - b a s e m e n t membrane zone antibodies by indirect immunofluorescence techniques. 303