- Email: [email protected]
Chronic pruritus in HIV-positive patients in the southeastern United States: Its prevalence and effect on quality of life
Chronic pruritus in HIV-positive patients in the southeastern United States: Its prevalence and effect on quality of life Shivani B. Kaushik, MD,a Felipe B. Cerci, MD,a Jill Miracle, MD,b Achyut Pokharel, MD,a Suephy C. Chen, MD, MS,c,d Yiong Huak Chan, PhD,e Aimee Wilkin, MD, MPH,b and Gil Yosipovitch, MDa Winston Salem, North Carolina; Atlanta, Georgia; and Singapore Background: Prevalence of chronic pruritus in HIV-positive patients is an underevaluated topic in the United States. The characteristics, severity, and quality of life (QOL) in patients with HIV and chronic pruritus have not been well documented using validated tools. Objectives: We sought to assess the prevalence and intensity of chronic pruritus and its effect on QOL in HIV-positive patients in a US population. Methods: HIV-positive patients (n = 201) were asked to complete a sociodemographic data form and 2 itch questionnaires. Patients with itching rated their itch intensity on a numeric visual analog scale. Laboratory parameters were obtained from patients’ medical records. Results: The prevalence of chronic itch in the study group was 45% with an average visual analog scale score of 5.93 during an itch episode. Patients with high visual analog scale score had significantly decreased QOL. Patients with HIV reported greater negative impact of pruritus on daily lives. Limitations: Because of the cross-sectional design, this study demonstrates an association between HIV and pruritus but cannot prove causation. Conclusion: Patients with HIV surveyed in a large clinic in the southeastern United States have a high prevalence of pruritus; HIV pruritus has a significant effect on QOL and itch is the most common skin manifestation found in this population. ( J Am Acad Dermatol 2014;70:659-64.) Key words: chronic pruritus; HIV; quality of life.
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wide spectrum of cutaneous manifestations are associated with HIV, and pruritus is one of the predominant symptoms for which patients with HIV seek the opinion of a dermatologist.1 Although these dermatoses are usually tolerable and controllable, they can sometimes severely diminish the quality of life (QOL) of patients.2 In particular, chronic pruritus has significant negative impact on QOL similar to that of chronic pain syndromes.3 From the Departments of Dermatologya and Internal Medicine, Section of Infectious Diseases,b Wake Forest University Baptist Medical Center, Winston Salem; Division of Dermatology, Atlanta Department of Veterans Affairs Medical Centerc; Department of Dermatology, Emory School of Medicine, Atlantad; and Biostatistics Unit, Yong Loo Lin School of Medicine, National University Health System, Singapore.e Funding sources: None. Conflicts of interest: None declared. Accepted for publication December 31, 2013.
Abbreviations used: ART: PPE: QOL: VAS:
antiretroviral therapy pruritic papular eruption quality of life visual analog scale
The prevalence of chronic pruritus in patients with HIV has been an underevaluated topic and has not been assessed in the United States in a comprehensive Reprint requests: Gil Yosipovitch, MD, Department of Dermatology and Temple Itch Center, Temple University School of Medicine, 3322 N Broad St, Second Floor, Medical Office Bldg, Philadelphia, PA 19140. E-mail: [email protected]. edu. Published online February 6, 2014. 0190-9622/$36.00 Ó 2014 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2013.12.015
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fashion. Although studies in the past have analyzed the asked to rate their average itch intensity during the past type and morphology of various skin disorders 2 months on a numeric visual analog scale (VAS) of 0 to affecting patients with HIV, none of these have 10.11 The subjects were also asked to rate a typical addressed the characteristics, severity, and QOL of episode of itch on the VAS. The pleasure of scratching patients with HIV and chronic pruritus. A recent study an itch was rated on a 10-point Likert scale (from 5 to from Spain reported a high prevalence of pruritus 15 where 5 represents ‘‘highly unpleasurable’’ and (31%) in patients with HIV even though many were on 15 represents ‘‘highly pleasurable’’). Another validated highly active antiretroviral questionnaire, ItchyQoL has therapy (ART) but it did not 22 unique items. This quesCAPSULE SUMMARY use validated tools to assess tionnaire contains 3 major subitch characteristics, severity, scales pertinent to patients Prevalence data of chronic itch, its and its impact on QOL.4,5 with pruritus: symptoms (Q1clinical characteristics, and effect on 6), functional limitations (Q7Chronic pruritus is a multidiquality of life in the HIV US population 13), and emotions (Q14-22). mensional subjective sensaare lacking. Participants were asked to rate tion that includes The prevalence of chronic pruritus is each item on a 1-to-5 scale (1 = psychological and functional high (45%) and patients with high never, 2 = rarely, 3 = someaspects and therefore it is intensity of itch are noted to have times, 4 = often, 5 = all the important to assess these meadecreased quality of life. time).9 Scoring of the ItchyQoL sures and the QOL of patients with HIV to more fully appreconsisted of 3 subscale scores Chronic pruritus is a common symptom ciate the impact of pruritus. and an overall score. We of HIV in the era of highly active The major aims of this compared subscale scores antiretroviral therapy and significantly cross-sectional study were to across demography, skin disreduces quality of life of patients with assess the prevalence and ineases, sensations associated HIV. Managing itch in the HIV population tensity of chronic pruritus and with itch, and comorbidities.9 is of significant importance. its effect on QOL in an outAll the participants were patient sample of ethnically examined by trained dermadiverse HIV-infected study group in the United States. tologists for presence of any skin diseases or Secondary aims were to: (1) assess skin manifestations cutaneous markers unique to HIV such as pruritic and their association to itch; and (2) examine whether papular eruption (PPE) and eosinophilic folliculitis. there is a correlation between disease state based on Laboratory parameters such as CD4 levels, viral load, CD4 count, viral load, other comorbidities, and deliver function tests, complete blood cell counts, and mographic features and pruritus. eosinophil counts and results of skin biopsy specimens if previously performed were obtained from the medical records of all the patients. Detailed METHODS information regarding comorbidities such as renal, This study was conducted from August 2012 to hepatic, thyroid, and sexually transmitted diseases December 2012 in the outpatient HIV clinic at the was also documented, as were medications. Wake Forest University School of Medicine, Winston Salem, NC, after approval by the medical center’s Statistical analysis institutional review board. All eligible HIV-positive All analyses were performed using software (SPSS patients (age $ 18 years) were asked to participate 16.0, IBM Corp, Armonk, NY). Descriptive statistics in the study and approximately 70% of them agreed for quantitative variables were presented as mean 6 to participate after signing an informed consent SD and as percentages for qualitative variables. form. In all, 201 patients were included in the study. Spearman correlation coefficients were presented All participants were asked to complete the to assess relationships between quantitative and following validated itch questionnaires: the shortordinal qualitative outcomes. Correlation between form itch questionnaire6-8 and the ItchyQoL.9,10 The skin diseases and QOL was determined by using the short-form itch questionnaire examines the severity Mann Whitney U test. Statistical significance was set of itch and its associated factors, and describes the at P less than .05. relationship to scratching.9 The ItchyQoL questionnaire focuses on patients’ QOL through examining symptoms, functional limitations, and emotions RESULTS related to itch. Between August 2012 and December 2012, 201 Survey participants were asked if they currently patients with a mean age of 47 years (range 21-100) experienced itch. All participants with itching were were enrolled in the study. Demographic d
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Table I. Descriptive characteristics of HIV-positive patients (N = 201) Gender Male Female Route of transmission Heterosexual
N (%) Race/ethnicity N (%) 124 (61) African American 152 (76) 77 (38) Caucasian 38 (19) Hispanic 9 (4) Other 2 (1) 98 (49) Overall health status* 79 (39) Poor
Men who have sex with men Intravenous 4 (2) drug use Blood transfusion 16 (8) Not known 4 (2)
11 (5)
Fair
61 (30)
Good Excellent
95 (48) 33 (16)
*As self-reported by participants.
characteristics of the study group are depicted in Table I. Of study participants, 76% were African American and 62% overall were men. Of the 201 patients assessed for pruritus, 95 (47%) reported itching on the day of physical examination. The prevalence of itch in HIV-positive women was 60% (n = 46 of 76) whereas only 39% (n = 49 of 125) of HIV-positive men experienced itch. This difference was statistically significant (P = .003). The prevalence of chronic itch defined as more than 6 weeks’ duration was 45% (n = 90). The mean itch intensity level reported was 5.1 6 2.8. The average VAS score for the subjects during an itch episode 5.93 6 2.31. Scratching was considered pleasurable by 54% of participants with chronic itch with a mean score of 1.18 6 3.08 on the Likert scale. The most commonly reported symptoms accompanying itching were sweating in 18 (9%) subjects followed by heat sensation in 11 (5.5%). Only 3 patients reported feeling pain within the area of itch. Nearly one third (30%) of participants reported 2 to 4 episodes of itch per day. In all, 77 (38%) patients reported more itching at night and 70 (35%) reported itching during the summer. There was no statistically significant relationship between duration of HIV infection and presence of pruritus. The most common dermatoses noted were xerosis (23%), fungal infections (12%), seborrheic dermatitis (9%), and eczema (7%). PPE was noted in 13 (6%) patients. The highest mean VAS score of 8.25 6 1.26 was noted for patients with lichen simplex chronicus followed closely by prurigo nodularis with a mean VAS score of 6.67 6 2.42. Of the 13 patients with PPE, 11 had itching with a mean VAS
Table II. Ranked prevalence of dermatologic diagnosis
Skin diseases
Xerosis Fungal* Seborrheic dermatitis Eczema Pruritic papular eruption Prurigo nodularis Lichen simplex chronicus Folliculitis Itch without rash Bitesy Psoriasis Scabies
No. of patients No. of with the patients disease, with itching, N (%) N (%)
Mean VAS score 6 SD
P value
.339 .307 .143
47 (23) 24 (12) 18 (9)
24 (27) 13 (15) 11 (12)
2.79 6 3.34 3.50 6 3.50 3.44 6 3.13
15 (7) 13 (6)
14 (16) 11 (12)
6.33 6 2.72 <.001 5.62 6 3.20 .003
6 (3) 4 (2)
6 (7) 4 (5)
4 3 3 1 1
1 3 3 1 1
(2) (1.5) (1.5) (0.5) (0.5)
(1) (3) (3) (1) (1)
6.67 6 2.42 8.25 6 1.26
.007 .038
6 4.50 6 1.00 6 1.53 60 60
.630 .088 .086 .445 .445
2.25 6.00 5.33 2.00 10.00
Bold indicate significant P values (\ .05). VAS, Visual analog scale. *Superficial fungal infections; encompasses tinea corporis, tinea cruris, and tinea pedis. y Broadly refers to insect or mosquito bites.
score of 5.62 6 3.20. Pruritus caused by eczema, prurigo nodularis, and PPE was found to be associated with worse QOL (P \.05). Detailed description of diseases and relevant statistical data are shown in Table II. QOL and pruritus Several interesting findings were observed from the score analysis of ItchyQoL. First, the average subscale scores demonstrate that emotion has the greatest impact among all the 3 domains of the ItchyQoL. Second, women have relatively higher scores than men in all 3 subsets (P \ .05). Third, prurigo nodularis and HIV-related dermatoses had significant impact on all domains whereas lichen simplex chronicus had a significant impact only on symptoms. Fourth, concomitant symptoms such as sweating and heat seem to contribute significantly to the QOL impact across all the domains unlike pain or cold. Significant descriptive statistics of ItchyQoL are depicted in Table III. The participants demonstrated that the pruritusrelated QOL was most affected by ‘‘needing to scratch’’ with highest mean score of 2.32 6 1.49 followed closely by ‘‘feeling frustrated’’ with a mean score of 2.12 6 1.47. This mean score depicts the average of responses to all the items. Participants with a high VAS score were noted to have decreased QOL with a significant correlation
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Table III. Significant descriptive statistics of ItchyQoL Subscales Symptoms Parameter
Gender Male (n = 125) Female (n = 76) Skin manifestation HIV dermatoses (n = 13) Prurigo nodularis (n = 6) Lichen simplex chronicus (n = 4) Sensations associated with itch Sweating (n = 18) Heat (n = 11)
Mean 6 SD
Functioning P value
Mean 6 SD
Emotions Mean 6 SD
P value
P value
10.21 6 5.50 11.65 6 5.56
.074
10.75 6 5.49 13.38 6 6.66
.003
14.44 6 8.79 17.93 6 10.2
.011
15.23 6 6.64 15.66 6 6.25 15.73 6 5.73
.003 .027 .068
14.69 6 6.38 16.66 6 9.24 15.00 6 5.47
.071 .041 .271
20.61 6 11.25 24.66 6 13.5 22.50 6 6.24
.057 .018 .148
15.00 6 4.95 14.80 6 5.47
\.001 .012
17.00 6 6.57 17.81 6 6.17
\.001 \.001
23.77 6 10.54 24.72 6 11.79
\.001 \.001
coefficient of 0.46 (P \.01). Those with itching had a total QOL score of 49.20 6 20.62 with a mean QOL score of 38.27 6 20.29. In general, HIV-infected patients reported greater negative impact of pruritus on their daily lives. Regardless of the cause of pruritus, there is an inverse correlation between the severity of pruritus and the QOL of the patient. There was no significant relationship between the presence of comorbidities and poor QOL. The prevalence of itch in participants with viral load 400 copies/mL or greater was 54% (n = 32 of 59) whereas only 41% (n = 58 of 142) of participants with viral load less than 400 copies/mL had itching. However, it did not reach statistical significance (P = .068) and a very weak correlation coefficient of 0.11 was recorded between VAS score and viral load. Mean CD4 count in patients with pruritus was 530 6 384 cells/L versus 570 6 421 cells/L in nonpruritic patients (P = .660). A similar pattern was noted in mean eosinophil count with 23 6 44 cells/ L in patients with pruritus and 17 6 30 cells/L in nonpruritic patients (P = .266). No significant association was noted between presence of pruritus and CD4 and eosinophil count. Coexisting comorbidities were recorded for all participants and the relevant data are displayed in Table IV. Of the 201 patients, 52 (26%) had a history of depression, 37 (18%) had hepatitis C, and substance abuse was documented in 12% of the participants. There was a trend toward more itch in participants with a history of depression, but it was not statistically significant. Interestingly, hepatitis C was more prevalent in nonpruritic patients. Among the 201 participants, 184 (91%) were receiving ART. Itching was reported in 45% of ART recipients and 41% of participants not on ART with no association between ART and itching (P = .075).
Table IV. Major comorbidities Pruritus, N (%) Comorbidities
Depression Hepatitis C Substance abuse Hepatitis B Chronic renal failure
N (%)
52 37 24 15 10
(26) (18) (12) (7) (5)
Yes
29 10 11 7 2
(33) (11) (46) (8) (2)
No
23 27 13 8 8
(21) (24) (54) (7) (7)
P value
.062 .016 .912 .878 .190
Concordantly, there was no relation between prevalence and severity of pruritus and the use of specific classes of ART. Patients on antihistamines had a significantly higher severity of itching and hence a higher mean VAS score (P \ .05). No association of any kind was seen between itching and any other class of medications.
DISCUSSION This study represents one of the first assessments of pruritus and its effect on QOL in HIV-positive patients in a population from the United States. Several important findings emerge from this study: first, patients with HIV in a southeastern US clinic population have a high prevalence of pruritus. Second, pruritus has a significant effect on QOL for patients with HIV. Third, itch appears to be the most common skin manifestation in patients with HIV in the current era of highly effective ART. The prevalence of chronic pruritus was 45% in our study group, which is higher than the recent study performed by Blanes et al4 in Spain (31%). This reported prevalence also resonates with the results of previous studies reporting that itching is a predominant presenting symptom in HIV-infected patients.1,12
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In concordance with the study by Blanes et al,4 we observed a higher proportion of pruritus in women with HIV. Although the impact of pruritus on emotion as a subscale was greater than its impact on functional limitation and symptoms in both men and women, there was a relatively higher emotional impact of pruritus on the QOL of women with HIV. Previous studies have shown that women tend to report more chronic pruritus than men.4,13 The negative impact of itch on patients’ QOL has also been demonstrated in previous studies for other skin diseases such as atopic dermatitis and psoriasis.14 Severity and chronicity of itch have been shown to correlate negatively with sleep, daily functioning, and QOL.15,16 The most frequent dermatoses noted in this study were xerosis (23%), fungal infection (12%), and seborrheic dermatitis (9%). However, their prevalence were similar in both pruritic and nonpruritic patients suggesting this is not the major cause of itch in patients with HIV.17,18 A higher prevalence of xerosis (51.2%) was noted in the study by Blanes et al.4 Although prurigo nodularis (3%) and lichen simplex chronicus (2%) were reported in few patients, they were highly associated with severe itch and significantly worse QOL. Both of these diseases were observed to affect the individual across all 3 domains of symptoms, function, and emotion.15 Sweating was a commonly reported associated symptom, which may be related to autonomic overactivity in patients with chronic pruritus.7 Sweating along with heat sensation had a significantly negative impact on symptoms, emotional, and functional aspects of patients’ QOL. Through the ItchyQoL, we are able to determine which aspect of pruritus most impacts the patients in relation to symptoms, functional impairment, and emotions. This may vary greatly among individuals and thus, can help personalize the treatment and advice offered. The higher VAS scores noted in participants on antihistamines might be an indirect measure of impact of itch requiring therapy. The dermatologic manifestations and associated pruritus are known to increase both in severity and frequency with the increase in viral loads and decline in CD4 count.19 In this population, patients with high viral loads ( $ 400 copies/mL) had relatively higher prevalence of pruritus (54%) as compared with 41% in participants with undetectable levels of viral loads (\400 copies/mL). However, it was not significant as previously reported. This is possibly a result of high percentage of participants on ART (91%) and fewer patients with very high viral loads. The mean eosinophil count was also slightly higher in pruritic patients. However, it is important to highlight that these laboratory parameters were not significantly
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different between patients with and without pruritus. These results are in concordance with findings from other studies.4,20,21 The pathogenesis of itch in HIV is poorly understood, but complex and multifactorial mechanisms of itch are recognized. Putative mechanisms include barrier damage, neuropathy, T-cell imbalance with shift to Th2 cytokine profile, resulting in eosinophilia and increased IgE levels, and elevated chemokines.1,2,22 This study should be interpreted in the context of several potential limitations: first, this study shows an association between pruritus and HIV but cannot prove causation. The cross-sectional design provides information regarding the prevalence and severity of symptoms and QOL of patients with HIV at 1 point of time and may not fully capture the effect of pruritus over a lifetime. The concordant assessment of current and chronic itch may decrease effect of recollection bias. Medical records review does not fully capture the scope of comorbidities and impact of potential modifiers such as substance abuse. In addition, this study did not account for any treatments administered for specific dermatologic conditions. During the recruitment process, study personnel offered participation in a short survey and skin examination by a dermatologist without discussing itch until after the informed consent process was completed to minimize a recruitment bias of patients with pruritus or active skin diseases. However, there is a possibility that there may be an overrepresentation of subjects who have symptoms including itch because these patients may be more likely to participate in a skin disease survey. The population size also did not allow for determination of the impact of individual medications on itch. This study includes patients from 1 site in the southeastern United States with a high proportion of minority patients and thus may not be fully generalizable to the larger US HIV population. Also because the survey was performed during the fall only, potential seasonal variation in itch or skin findings are not addressed. In conclusion, chronic pruritus is common in HIVpositive individuals in the current era of effective ART and has an adverse impact on QOL. There is a need to assess and treat itch as part of the management of chronic HIV infection. REFERENCES 1. Serling SLC, Leslie K, Maurer T. Approach to pruritus in the adult HIV-positive patient. Semin Cutan Med Surg 2011;30:101-6. 2. Duque MI, Yosipovitch G, Pegram PS. Itch in HIV-infected patients. In: Yosipovitch G, Greaves MW, Fleischer AB, McGlone F, editors. Itch basic mechanisms and therapy. New York (NY): Marcel Dekker; 2004. pp. 219-30.
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3. Kini SP, DeLong LK, Veledar E, Mckenzie-Brown AM, Schaufele M, Chen SC. The impact of pruritus on quality of life. Arch Dermatol 2011;147:1153-6. 4. Blanes M, Belinchon I, Portilla J, Betloch I, Reus S, Sanchez-Paya J. Pruritus in HIV-infected patients in the era of combination antiretroviral therapy: a study of its prevalence and causes. Int J STD AIDS 2012;23:255-7. 5. Mirmirani P, Maurer T, Berger T, Sands LP, Chren MM. Skin-related quality of life in HIV-infected patients on highly active antiretroviral therapy. J Cutan Med Surg 2002;6:10-5. 6. Dawn A, Papoiu AD, Chan YH, Rapp SR, Rassette N, Yosipovitch G. Itch characteristics in atopic dermatitis: results of a web-based questionnaire. Br J Dermatol 2009;160:642-4. 7. O’Neill JL, Chan YH, Rapp SR, Yosipovitch G. Differences in itch characteristics between psoriasis and atopic dermatitis patients: results of a web-based questionnaire. Acta Derm Venereol 2011;91:537-40. 8. Weisshaar E, Gieler U, Kupfer J, Furue M, Saeki H, Yosipovitch G. Questionnaires to assess chronic itch: a consensus paper of the special interest group of the international forum on the study of itch. Acta Derm Venereol 2012;92:493-6. 9. Desai NS, Poindexter GB, Monthrope YM, Bendeck SE, Swerlick RA, Chen SC. A pilot quality of life instrument for pruritus. J Am Acad Dermatol 2008;59:234-44. 10. Yosipovitch G, Zucker I, Boner G, Gafter U, Shapira Y, David M. A questionnaire for the assessment of pruritus: validation in uremic patients. Acta Derm Venereol 2001;81:108-11. 11. Krause K, Kessler B, Weller K, Veidt J, Chen SC, Martus P, et al. German version of ItchyQol: validation and initial clinical findings. Acta Derm Venereol 2013;93:562-8. 12. Zancanaro PCQ, McGirt LY, Mamelak AJ, Nguyen R, Martins CR. Cutaneous manifestations of HIV in the era of highly active
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antiretroviral therapy: an institutional urban clinic experience. J Am Acad Dermatol 2006;54:581-8. Stander S, Stumpf A, Osada N, Wilp S, Chatzigeorgakidis E, Pfleiderer B. Gender differences in chronic pruritus: women present different morbidity, more scratch lesions and higher burden. Br J Dermatol 2013;168:1273-80. Tey HL, Wallengren J, Yosipovitch G. Psychosomatic factors in pruritus. Clin Dermatol 2013;31:31-40. Erturk IE, Arican O, Omurlu IK, Sut N. Effect of pruritus on quality of life: a preliminary study. Ann Dermatol 2012;24: 406-12. Hudson A, Kirskey K, Holzemer W. The influence of symptoms on quality of life among HIV-infected women. West J Nurs Res 2004;26:9. Rodwell G, Berger TG. Pruritus and cutaneous inflammatory conditions in HIV disease. Clin Dermatol 2000;18:479-84. Rigopoulos D, Paparizos V, Katsambas A. Cutaneous markers of HIV infection. Clin Dermatol 2004;22:487-98. Goldstein B, Berman B, Sukenik E. Correlation of skin disorders with CD4 lymphocyte counts in patients with HIV/AIDS. J Am Acad Dermatol 1997;36:262-4. Milazzo F, Piconi S, Trabattoni D, Magni C, Coen M, Capetti A, et al. Intractable pruritus in HIV infection: immunologic characterization. Allergy 1999;54:266-72. Singh H, Singh P, Tiwari P, Dey V, Dulhani N, Singh A. Dermatological manifestations in HIV-infected patients at a tertiary care hospital in a tribal (Bastar) region of Chattisgarh, India. Indian J Dermatol 2009;54:338-41. Yokobayashi H, Sugaya M, Miyagaki T, Kai H, Suga H, Yamada D, et al. Analysis of serum chemokine levels in patients with HIV-associated eosinophilic folliculitis. J Eur Acad Dermatol Venereol 2013;27:e212-6.
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wide spectrum of cutaneous manifestations are associated with HIV, and pruritus is one of the predominant symptoms for which patients with HIV seek the opinion of a dermatologist.1 Although these dermatoses are usually tolerable and controllable, they can sometimes severely diminish the quality of life (QOL) of patients.2 In particular, chronic pruritus has significant negative impact on QOL similar to that of chronic pain syndromes.3 From the Departments of Dermatologya and Internal Medicine, Section of Infectious Diseases,b Wake Forest University Baptist Medical Center, Winston Salem; Division of Dermatology, Atlanta Department of Veterans Affairs Medical Centerc; Department of Dermatology, Emory School of Medicine, Atlantad; and Biostatistics Unit, Yong Loo Lin School of Medicine, National University Health System, Singapore.e Funding sources: None. Conflicts of interest: None declared. Accepted for publication December 31, 2013.
Abbreviations used: ART: PPE: QOL: VAS:
antiretroviral therapy pruritic papular eruption quality of life visual analog scale
The prevalence of chronic pruritus in patients with HIV has been an underevaluated topic and has not been assessed in the United States in a comprehensive Reprint requests: Gil Yosipovitch, MD, Department of Dermatology and Temple Itch Center, Temple University School of Medicine, 3322 N Broad St, Second Floor, Medical Office Bldg, Philadelphia, PA 19140. E-mail: [email protected]. edu. Published online February 6, 2014. 0190-9622/$36.00 Ó 2014 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2013.12.015
659
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660 Kaushik et al
APRIL 2014
fashion. Although studies in the past have analyzed the asked to rate their average itch intensity during the past type and morphology of various skin disorders 2 months on a numeric visual analog scale (VAS) of 0 to affecting patients with HIV, none of these have 10.11 The subjects were also asked to rate a typical addressed the characteristics, severity, and QOL of episode of itch on the VAS. The pleasure of scratching patients with HIV and chronic pruritus. A recent study an itch was rated on a 10-point Likert scale (from 5 to from Spain reported a high prevalence of pruritus 15 where 5 represents ‘‘highly unpleasurable’’ and (31%) in patients with HIV even though many were on 15 represents ‘‘highly pleasurable’’). Another validated highly active antiretroviral questionnaire, ItchyQoL has therapy (ART) but it did not 22 unique items. This quesCAPSULE SUMMARY use validated tools to assess tionnaire contains 3 major subitch characteristics, severity, scales pertinent to patients Prevalence data of chronic itch, its and its impact on QOL.4,5 with pruritus: symptoms (Q1clinical characteristics, and effect on 6), functional limitations (Q7Chronic pruritus is a multidiquality of life in the HIV US population 13), and emotions (Q14-22). mensional subjective sensaare lacking. Participants were asked to rate tion that includes The prevalence of chronic pruritus is each item on a 1-to-5 scale (1 = psychological and functional high (45%) and patients with high never, 2 = rarely, 3 = someaspects and therefore it is intensity of itch are noted to have times, 4 = often, 5 = all the important to assess these meadecreased quality of life. time).9 Scoring of the ItchyQoL sures and the QOL of patients with HIV to more fully appreconsisted of 3 subscale scores Chronic pruritus is a common symptom ciate the impact of pruritus. and an overall score. We of HIV in the era of highly active The major aims of this compared subscale scores antiretroviral therapy and significantly cross-sectional study were to across demography, skin disreduces quality of life of patients with assess the prevalence and ineases, sensations associated HIV. Managing itch in the HIV population tensity of chronic pruritus and with itch, and comorbidities.9 is of significant importance. its effect on QOL in an outAll the participants were patient sample of ethnically examined by trained dermadiverse HIV-infected study group in the United States. tologists for presence of any skin diseases or Secondary aims were to: (1) assess skin manifestations cutaneous markers unique to HIV such as pruritic and their association to itch; and (2) examine whether papular eruption (PPE) and eosinophilic folliculitis. there is a correlation between disease state based on Laboratory parameters such as CD4 levels, viral load, CD4 count, viral load, other comorbidities, and deliver function tests, complete blood cell counts, and mographic features and pruritus. eosinophil counts and results of skin biopsy specimens if previously performed were obtained from the medical records of all the patients. Detailed METHODS information regarding comorbidities such as renal, This study was conducted from August 2012 to hepatic, thyroid, and sexually transmitted diseases December 2012 in the outpatient HIV clinic at the was also documented, as were medications. Wake Forest University School of Medicine, Winston Salem, NC, after approval by the medical center’s Statistical analysis institutional review board. All eligible HIV-positive All analyses were performed using software (SPSS patients (age $ 18 years) were asked to participate 16.0, IBM Corp, Armonk, NY). Descriptive statistics in the study and approximately 70% of them agreed for quantitative variables were presented as mean 6 to participate after signing an informed consent SD and as percentages for qualitative variables. form. In all, 201 patients were included in the study. Spearman correlation coefficients were presented All participants were asked to complete the to assess relationships between quantitative and following validated itch questionnaires: the shortordinal qualitative outcomes. Correlation between form itch questionnaire6-8 and the ItchyQoL.9,10 The skin diseases and QOL was determined by using the short-form itch questionnaire examines the severity Mann Whitney U test. Statistical significance was set of itch and its associated factors, and describes the at P less than .05. relationship to scratching.9 The ItchyQoL questionnaire focuses on patients’ QOL through examining symptoms, functional limitations, and emotions RESULTS related to itch. Between August 2012 and December 2012, 201 Survey participants were asked if they currently patients with a mean age of 47 years (range 21-100) experienced itch. All participants with itching were were enrolled in the study. Demographic d
d
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Table I. Descriptive characteristics of HIV-positive patients (N = 201) Gender Male Female Route of transmission Heterosexual
N (%) Race/ethnicity N (%) 124 (61) African American 152 (76) 77 (38) Caucasian 38 (19) Hispanic 9 (4) Other 2 (1) 98 (49) Overall health status* 79 (39) Poor
Men who have sex with men Intravenous 4 (2) drug use Blood transfusion 16 (8) Not known 4 (2)
11 (5)
Fair
61 (30)
Good Excellent
95 (48) 33 (16)
*As self-reported by participants.
characteristics of the study group are depicted in Table I. Of study participants, 76% were African American and 62% overall were men. Of the 201 patients assessed for pruritus, 95 (47%) reported itching on the day of physical examination. The prevalence of itch in HIV-positive women was 60% (n = 46 of 76) whereas only 39% (n = 49 of 125) of HIV-positive men experienced itch. This difference was statistically significant (P = .003). The prevalence of chronic itch defined as more than 6 weeks’ duration was 45% (n = 90). The mean itch intensity level reported was 5.1 6 2.8. The average VAS score for the subjects during an itch episode 5.93 6 2.31. Scratching was considered pleasurable by 54% of participants with chronic itch with a mean score of 1.18 6 3.08 on the Likert scale. The most commonly reported symptoms accompanying itching were sweating in 18 (9%) subjects followed by heat sensation in 11 (5.5%). Only 3 patients reported feeling pain within the area of itch. Nearly one third (30%) of participants reported 2 to 4 episodes of itch per day. In all, 77 (38%) patients reported more itching at night and 70 (35%) reported itching during the summer. There was no statistically significant relationship between duration of HIV infection and presence of pruritus. The most common dermatoses noted were xerosis (23%), fungal infections (12%), seborrheic dermatitis (9%), and eczema (7%). PPE was noted in 13 (6%) patients. The highest mean VAS score of 8.25 6 1.26 was noted for patients with lichen simplex chronicus followed closely by prurigo nodularis with a mean VAS score of 6.67 6 2.42. Of the 13 patients with PPE, 11 had itching with a mean VAS
Table II. Ranked prevalence of dermatologic diagnosis
Skin diseases
Xerosis Fungal* Seborrheic dermatitis Eczema Pruritic papular eruption Prurigo nodularis Lichen simplex chronicus Folliculitis Itch without rash Bitesy Psoriasis Scabies
No. of patients No. of with the patients disease, with itching, N (%) N (%)
Mean VAS score 6 SD
P value
.339 .307 .143
47 (23) 24 (12) 18 (9)
24 (27) 13 (15) 11 (12)
2.79 6 3.34 3.50 6 3.50 3.44 6 3.13
15 (7) 13 (6)
14 (16) 11 (12)
6.33 6 2.72 <.001 5.62 6 3.20 .003
6 (3) 4 (2)
6 (7) 4 (5)
4 3 3 1 1
1 3 3 1 1
(2) (1.5) (1.5) (0.5) (0.5)
(1) (3) (3) (1) (1)
6.67 6 2.42 8.25 6 1.26
.007 .038
6 4.50 6 1.00 6 1.53 60 60
.630 .088 .086 .445 .445
2.25 6.00 5.33 2.00 10.00
Bold indicate significant P values (\ .05). VAS, Visual analog scale. *Superficial fungal infections; encompasses tinea corporis, tinea cruris, and tinea pedis. y Broadly refers to insect or mosquito bites.
score of 5.62 6 3.20. Pruritus caused by eczema, prurigo nodularis, and PPE was found to be associated with worse QOL (P \.05). Detailed description of diseases and relevant statistical data are shown in Table II. QOL and pruritus Several interesting findings were observed from the score analysis of ItchyQoL. First, the average subscale scores demonstrate that emotion has the greatest impact among all the 3 domains of the ItchyQoL. Second, women have relatively higher scores than men in all 3 subsets (P \ .05). Third, prurigo nodularis and HIV-related dermatoses had significant impact on all domains whereas lichen simplex chronicus had a significant impact only on symptoms. Fourth, concomitant symptoms such as sweating and heat seem to contribute significantly to the QOL impact across all the domains unlike pain or cold. Significant descriptive statistics of ItchyQoL are depicted in Table III. The participants demonstrated that the pruritusrelated QOL was most affected by ‘‘needing to scratch’’ with highest mean score of 2.32 6 1.49 followed closely by ‘‘feeling frustrated’’ with a mean score of 2.12 6 1.47. This mean score depicts the average of responses to all the items. Participants with a high VAS score were noted to have decreased QOL with a significant correlation
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Table III. Significant descriptive statistics of ItchyQoL Subscales Symptoms Parameter
Gender Male (n = 125) Female (n = 76) Skin manifestation HIV dermatoses (n = 13) Prurigo nodularis (n = 6) Lichen simplex chronicus (n = 4) Sensations associated with itch Sweating (n = 18) Heat (n = 11)
Mean 6 SD
Functioning P value
Mean 6 SD
Emotions Mean 6 SD
P value
P value
10.21 6 5.50 11.65 6 5.56
.074
10.75 6 5.49 13.38 6 6.66
.003
14.44 6 8.79 17.93 6 10.2
.011
15.23 6 6.64 15.66 6 6.25 15.73 6 5.73
.003 .027 .068
14.69 6 6.38 16.66 6 9.24 15.00 6 5.47
.071 .041 .271
20.61 6 11.25 24.66 6 13.5 22.50 6 6.24
.057 .018 .148
15.00 6 4.95 14.80 6 5.47
\.001 .012
17.00 6 6.57 17.81 6 6.17
\.001 \.001
23.77 6 10.54 24.72 6 11.79
\.001 \.001
coefficient of 0.46 (P \.01). Those with itching had a total QOL score of 49.20 6 20.62 with a mean QOL score of 38.27 6 20.29. In general, HIV-infected patients reported greater negative impact of pruritus on their daily lives. Regardless of the cause of pruritus, there is an inverse correlation between the severity of pruritus and the QOL of the patient. There was no significant relationship between the presence of comorbidities and poor QOL. The prevalence of itch in participants with viral load 400 copies/mL or greater was 54% (n = 32 of 59) whereas only 41% (n = 58 of 142) of participants with viral load less than 400 copies/mL had itching. However, it did not reach statistical significance (P = .068) and a very weak correlation coefficient of 0.11 was recorded between VAS score and viral load. Mean CD4 count in patients with pruritus was 530 6 384 cells/L versus 570 6 421 cells/L in nonpruritic patients (P = .660). A similar pattern was noted in mean eosinophil count with 23 6 44 cells/ L in patients with pruritus and 17 6 30 cells/L in nonpruritic patients (P = .266). No significant association was noted between presence of pruritus and CD4 and eosinophil count. Coexisting comorbidities were recorded for all participants and the relevant data are displayed in Table IV. Of the 201 patients, 52 (26%) had a history of depression, 37 (18%) had hepatitis C, and substance abuse was documented in 12% of the participants. There was a trend toward more itch in participants with a history of depression, but it was not statistically significant. Interestingly, hepatitis C was more prevalent in nonpruritic patients. Among the 201 participants, 184 (91%) were receiving ART. Itching was reported in 45% of ART recipients and 41% of participants not on ART with no association between ART and itching (P = .075).
Table IV. Major comorbidities Pruritus, N (%) Comorbidities
Depression Hepatitis C Substance abuse Hepatitis B Chronic renal failure
N (%)
52 37 24 15 10
(26) (18) (12) (7) (5)
Yes
29 10 11 7 2
(33) (11) (46) (8) (2)
No
23 27 13 8 8
(21) (24) (54) (7) (7)
P value
.062 .016 .912 .878 .190
Concordantly, there was no relation between prevalence and severity of pruritus and the use of specific classes of ART. Patients on antihistamines had a significantly higher severity of itching and hence a higher mean VAS score (P \ .05). No association of any kind was seen between itching and any other class of medications.
DISCUSSION This study represents one of the first assessments of pruritus and its effect on QOL in HIV-positive patients in a population from the United States. Several important findings emerge from this study: first, patients with HIV in a southeastern US clinic population have a high prevalence of pruritus. Second, pruritus has a significant effect on QOL for patients with HIV. Third, itch appears to be the most common skin manifestation in patients with HIV in the current era of highly effective ART. The prevalence of chronic pruritus was 45% in our study group, which is higher than the recent study performed by Blanes et al4 in Spain (31%). This reported prevalence also resonates with the results of previous studies reporting that itching is a predominant presenting symptom in HIV-infected patients.1,12
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In concordance with the study by Blanes et al,4 we observed a higher proportion of pruritus in women with HIV. Although the impact of pruritus on emotion as a subscale was greater than its impact on functional limitation and symptoms in both men and women, there was a relatively higher emotional impact of pruritus on the QOL of women with HIV. Previous studies have shown that women tend to report more chronic pruritus than men.4,13 The negative impact of itch on patients’ QOL has also been demonstrated in previous studies for other skin diseases such as atopic dermatitis and psoriasis.14 Severity and chronicity of itch have been shown to correlate negatively with sleep, daily functioning, and QOL.15,16 The most frequent dermatoses noted in this study were xerosis (23%), fungal infection (12%), and seborrheic dermatitis (9%). However, their prevalence were similar in both pruritic and nonpruritic patients suggesting this is not the major cause of itch in patients with HIV.17,18 A higher prevalence of xerosis (51.2%) was noted in the study by Blanes et al.4 Although prurigo nodularis (3%) and lichen simplex chronicus (2%) were reported in few patients, they were highly associated with severe itch and significantly worse QOL. Both of these diseases were observed to affect the individual across all 3 domains of symptoms, function, and emotion.15 Sweating was a commonly reported associated symptom, which may be related to autonomic overactivity in patients with chronic pruritus.7 Sweating along with heat sensation had a significantly negative impact on symptoms, emotional, and functional aspects of patients’ QOL. Through the ItchyQoL, we are able to determine which aspect of pruritus most impacts the patients in relation to symptoms, functional impairment, and emotions. This may vary greatly among individuals and thus, can help personalize the treatment and advice offered. The higher VAS scores noted in participants on antihistamines might be an indirect measure of impact of itch requiring therapy. The dermatologic manifestations and associated pruritus are known to increase both in severity and frequency with the increase in viral loads and decline in CD4 count.19 In this population, patients with high viral loads ( $ 400 copies/mL) had relatively higher prevalence of pruritus (54%) as compared with 41% in participants with undetectable levels of viral loads (\400 copies/mL). However, it was not significant as previously reported. This is possibly a result of high percentage of participants on ART (91%) and fewer patients with very high viral loads. The mean eosinophil count was also slightly higher in pruritic patients. However, it is important to highlight that these laboratory parameters were not significantly
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different between patients with and without pruritus. These results are in concordance with findings from other studies.4,20,21 The pathogenesis of itch in HIV is poorly understood, but complex and multifactorial mechanisms of itch are recognized. Putative mechanisms include barrier damage, neuropathy, T-cell imbalance with shift to Th2 cytokine profile, resulting in eosinophilia and increased IgE levels, and elevated chemokines.1,2,22 This study should be interpreted in the context of several potential limitations: first, this study shows an association between pruritus and HIV but cannot prove causation. The cross-sectional design provides information regarding the prevalence and severity of symptoms and QOL of patients with HIV at 1 point of time and may not fully capture the effect of pruritus over a lifetime. The concordant assessment of current and chronic itch may decrease effect of recollection bias. Medical records review does not fully capture the scope of comorbidities and impact of potential modifiers such as substance abuse. In addition, this study did not account for any treatments administered for specific dermatologic conditions. During the recruitment process, study personnel offered participation in a short survey and skin examination by a dermatologist without discussing itch until after the informed consent process was completed to minimize a recruitment bias of patients with pruritus or active skin diseases. However, there is a possibility that there may be an overrepresentation of subjects who have symptoms including itch because these patients may be more likely to participate in a skin disease survey. The population size also did not allow for determination of the impact of individual medications on itch. This study includes patients from 1 site in the southeastern United States with a high proportion of minority patients and thus may not be fully generalizable to the larger US HIV population. Also because the survey was performed during the fall only, potential seasonal variation in itch or skin findings are not addressed. In conclusion, chronic pruritus is common in HIVpositive individuals in the current era of effective ART and has an adverse impact on QOL. There is a need to assess and treat itch as part of the management of chronic HIV infection. REFERENCES 1. Serling SLC, Leslie K, Maurer T. Approach to pruritus in the adult HIV-positive patient. Semin Cutan Med Surg 2011;30:101-6. 2. Duque MI, Yosipovitch G, Pegram PS. Itch in HIV-infected patients. In: Yosipovitch G, Greaves MW, Fleischer AB, McGlone F, editors. Itch basic mechanisms and therapy. New York (NY): Marcel Dekker; 2004. pp. 219-30.
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