|
Note: Tables and figures
of the article can be accessed and seen in the PDF file.
Background
“Infectious diseases will last as long as humanity
itself”
Diseases are curse to mankind and HIV/AIDS has worsened
it. According to recent Data, 33.2 million [30.6m-36.1m]
are living with HIV worldwide, of which 2.5 million are
newly infected cases in 2007 and 2.1 million died of
AIDS in 2007 (UNAIDS update, 2007). Data from
NACO says 2.5 million are HIV infected in India &
Karnataka is one of the high prevalence states (NACO
document, 2006). HIV infection produces a
panorama of mucocutaneous manifestations, which may be
the presenting feature of the disease. This ranges from
macular, roseola like rash in the acute seroconversion
syndrome to extensive end-stage Kaposi sarcoma.
Dermatological features of HIV disease can be seen
throughout the course of the HIV infection. So early
diagnosis & early institution of therapy is required.
With the advent of HAART, the course of HIV/AIDS has
been significantly changed and thus associated
dermatological lesions also (Maurer and Lori,
2004).Certain study showed dermatological lesions are
indicators of immune status of the individuals. So here
is an attempt to find the prevalence of dermatological
lesions in HIV/AIDS infected their association with
CD4+ cell count and to compare the prevalence of
dermatological lesions between patients on HAART and
patients not on HAART since 50% of the study populations
are on HAART.
In this
research work, 350 cases of HIV with skin lesions are
studied of which 50% are on HAART. [Lamivudine,
Stavudine & Nevirapine provided by NACO under brand name
Emtri 30/40] & the remaining 50% were not on HAART.
Methodology and Materials
Study design:
Cross-sectional study
Type of the study:
Hospital based cross sectional study
Sampling technique:
Simple random sampling.
Total
number of new cases with mucocutaneous manifestations
and those patients with mucocutaneous manifestation
already on treatment for the year 2005-2006 was taken
and sampling was done using software SPSS version 13.
Sample size: 350
members out of which 175 are on HAART (cat-2), and
remaining 175 members are not on HAART (cat-1).
The sample size was calculated by taking prevalence of
skin manifestations among HIV positive patients as
39.3%. Sample size was calculated at 5% significant
level and 10% error using software SPSS version 13.
Method of the study:
The study was conducted at the Skin and STD Department
of Krishna Rajendra (K.R) Hospital allied to the Mysore
Medical College and Research Institute, Karnataka from
August 2007 to October 2008. The study group includes
175 patients who presented with a symptom of one of the
mucocutaneous lesions. They did not know if they were
HIV infected. After they were tested they were found to
be positive and were included in the study.
Another
175 HIV positive patients, who are on HAART presenting
with some mucocutaneous manifestations were procured
from ANTI RETROVIRAL CENTRE of our hospital and were
involved in the study after confirming the below
mentioned criteria.
Inclusion criteria
1. HIV
positive patients (positivity confirmed by ELISA method
at VCTC centre of our hospital) giving consent to the
study.
2. Age
between 16 years to 60 years old.
Procedure
Before
involving the patient in the study, depending on their
educational status, written informed consent were
obtained from the patient/legal guardian in English.
Clearance from the institutional ethics committee was
also obtained, Data was collected based on the proforma,
which includes demographic profile and clinical
findings. Findings were noted by the student under the
guidance of the guiding professor. Finally, counseling
was done regarding hygiene and diet.
Laboratory Investigations
1. HIV
status was confirmed by ELISA method at VCTC centre of
our hospital
2. Base
line investigations were done to all patients such as Hb%,
peripheral blood smear examination (PBS).
3. CD4+
count was estimated by FACS (fluorescence activated Cell
sorter) count system at the department of Microbiology.
4.
Potassium hydroxide (KOH) preparation was used to
confirm Dermatophytosis.
5. VDRL
tests were done to confirm syphilis infection.
Results
When
socio-demographic profile was considered male and female
patients are almost equal (Table 1). With low
socioeconomic history, most of them acquired the
infection from heterosexual contact. Among which about
90% of the female patients acquired from their husband.
When
category I patients were considered; i.e. those who
presented without the knowledge of their HIV status,
Oral Candidiasis was the leading presenting complaint
seen in 28% of the study population (Table 6). It is
followed by Molluscum Contagiosum (24%) and then by
Condyloma Acuminatum (20%) which was seen only in male
patients and Multidermatomal Herpes Zoster (16%) (Table
2). So any patient with these symptoms can be suspected
as a case of HIV if other conditions are ruled out. When
all the infectious mucocutaneous manifestations were
considered together, viral infections comprised of 56
%(196); among which 71.42 %(140) were in
cat-1(non-HAART) And 28.58 %(56) in
cat-2(under-HAART).This shows a significant reduction in
viral opportunistic infection [chi-square=5.143:p<.023]
among patients after the initiation of HAART[median
duration of HAART in our study group was 6 months and
combination used in our set up was Lamivudine, Stavudine
and Nevirapine under the brand name Emtri 40/30]. One
case of Pityriasis Rosea, resistant to routine mode of
treatment was seen, but no other literature mentions its
association. So, further studies are required in this
line.
When the prevalence of dermatological lesions of
patients who are on HAART [Emtriàlamivudine,
Stavudine and Nevirapine, with median duration of 6
months], was compared with that of category I
(non-HAART), there was significant reduction in the
prevalence of dermatological viral infections in Cat II
[under HAART – chi square = 5.134; p< 0.023] (Table 10).
But the prevalence of bacterial and fungal infections
showed no change [p = 0.763 (NS) and p = 0.827 (NS)
respectively] (Table 11 and 12). When non-infectious
lesions were considered, there was a significant [chi
square = 4.50; p <0.034 (S)] increase in the prevalence
among Cat II (under HAART) which was accounted by
absolute increase in drug eruption and pruritic papular
eruption (Table 13).
Discussion
Out of
350 cases studied, 52 % (182) were males and 48 % (168)
were females. The subjects between 26-35years of age
group were significantly high [chi-square=18.60;
p<0.005]. Among which, we had 24 % (84) in 26-30 year
age group and 30 % (105) in 31-35 year age group. This
correlated with Bravo et al. (2006) who found out that
the most affected age group was 30 to 39yrs-51%. The
frequency of males and females in this age group was
almost similar. Only 4 % (14) of individuals were in
16-20 years and none in between 51-60years. Thus study
shows the high prevalence of HIV/AIDS in middle aged
population resulting in considerable reduction in the
manpower and increase in the economic burden of the
nation (NACO Document, 2006).
When
occupation was considered, 48% (168) were involved in
unskilled occupation [chi-square=14.8; p<.002], among
which female patients constituted for 75% (126) of the
total. It is followed by skilled worker, i.e. 22% (77),
in which male patients showed an upper hand which is
followed by farmers 16 % (56) and semiskilled workers 14
% (49). This correlates with Singh et al. (2009) whose
study also consisted of 46% unskilled workers, semi-
skilled workers formed 23% and farmers formed 5% of the
group. Mode of acquiring the disease among the study
group was absolutely heterosexual, no other modes were
reported. This is similar to Singh et al. (2009) who
reported 94.16% heterosexual transmission. In our study,
28% (98) denied any mode of transmission, while the
other 72% (252) admitted the heterosexual mode of
transmission. Of them 36 % (126), who were all females
acquired from their spouse. In remaining 36 % (126), who
acquired from external source, 88.8 % (112) were males
and 11.11 % (14) were females. Most of the males
acquired from Commercial sex workers (CSW) and out of 2
females 1 was CSW and other admitted her high risk
behavior.
From
this we can conclude that low socioeconomic status may
be one of the associated factors for rampant HIV/AIDS in
our country.
Condyloma acuminatum 14 % (49) was the common diagnosis
among the viral OIs, of which 71.4%(35) cases were cat-1
and 28.5%(14) cases in cat-2 which shows decrease in the
prevalence among HAART initiated patients .Mean CD4+
cell count among cat-1 was 197cell/mm3 and in
cat-2 was 319cell/mm3.When compared to Munoz
Perez, Rodriguez-Pichardo, , Camacho, & Colmenero,(1998)
this is bit high as they report that HIV infection
itself predisposes to an increased risk of HPV infection
that is not directly related to the degree of
immunosuppression. Studies by Shobhana, Guha, and Neogi
DK (2004) show still low i.e. 0.5%. Our study is
comparable to Hengge et al. (2000) as they also found a
significant decrease in the prevalence of Condyloma
acuminatum in their study recruited after the initiation
of HAART.
Herpes
zoster (HZ) was the next most common [12 % (42)]
diagnosis.This is comparable to Kumarasamy et al. (2000)
and Mbuagbaw et al. (2006) who reported a prevalence of
11.2% and 9.7% respectively. In our study, among the 12%
(42) of cases, 67 % (28) cases were in cat-1 and 33 %
(14) cases were in cat-2. Mean CD4+ count for cat-1 was
273.2 cell/mm3, but in cat-2 mean CD4+ Count
was significantly low i.e. 56 cell/mm3.This
shows that HZ can occur at all degree of
immunosuppression. Hengge, Ulrich R, Franz, Barbara,
Goos(2000) reports the HZ incidence is directly related
to the viral load. This may be the reason why our
patients (cat-2) had significant high prevalence as
their CD4+ Count was too less, which is the indirect
evidence of high viral load and thus they are on HAART.
Molluscum contagiosum [12 % (42)] was seen only in cat-1
patients with mean CD4+ of 155.1cell/mm3
which (CD4+ Count) is higher than that reported by Sen
et al. (2009) who reported a mean CD4 count of
98cells/cu.mm. This finding is significant as no cases
were seen in patients under HAART (cat-2).
Herpes
simplex virus (HSV) genitalis [10 % (35)], HSV labialis
[2 % (7)] were frequent viral OIs. Among HSV Genitalis,
80 % (28) of the cases were in cat-1 and only 20 % (7)
in cat-2.Our study is comparable to Shobhana, Guha, and
Neogi (2004) which shows (8%) with mean CD4+ Count of
187cell/mm3 against 211.5 of our study, but
Nair SP , Moorty KP, Suprakasan S (2003) reports very
low prevalence (2.74%). Our study was also comparable to
Munoz-Perez, et al. (1998) as they also reported reduced
prevalence in “under HAART” category. HSV labialis was
seen only in Cat-2 and no other study reports
association, this may be coincidental.
Verruca
vulgaris 6 % (21), of which 33 % (7) were in cat-1 and
almost double cases in cat-2. This is comparable to
Hengge et al. (2000) as they also reported the increase
in prevalence in their “under HAART” category.
Bacterial skin infections were seen in 22 % (77) of the
subjects, which was suspected to be caused by
Staphylococcus aureus. This is comparable to Bhandary et
al. (1997) who report a prevalence of 25%. When
individual lesions such as Furuncle (8%), Carbuncle
(2%), Folliculitis (8%), Abscess (2%) are considered it
is comparable to Munoz Perez et al. (2008) reported 1.6%
prevalence of folliculitis, which is lower compared to
our study but a CD4 count of 127.3cells/cu.mm which is
comparable to CD4 count of 130cells/cu.mm in our study.
When cat-1[45.54 % (35)] and cat-2[54.45 %(42)]was
considered, there is slight increase in cat-2, even when
they are in HAART. This may be attributed to the poor
socio economic status of our study population. 7 (4%)
cases of syphilis were reported in cat-1 and none in
cat-2.
Fungal
infection comprised of 42 % (147), of which
Dermatophytes accounted for 22 % (77), oral
candidiasis-14 % (49), Onychomycosis-4 % (56),
pityriasis versicolor-2% (7). When Dermatophytes 22 %
(77) were considered, it was slightly higher than other
studies such as Samet et al. (1999) who reported a
prevalence of 34%. This is due to lower socioeconomic
status of our study population. When cat-1[18.18 % (14)]
and cat-2 [81.81 % (63)] were considered separately,
there was significant high prevalence [p<.05] among
cat-2 group. Individual lesion of cat-1 such as tinea
pedis [4 % (7)] and tinea cruris [4 % (7)] with mean
CD4+ count of 79cell/mm3 were comparable to
Munoz Perez et al. (1998),But prevalence of lesions in
cat-2 were significantly high may be due longer duration
of mean HIV positive life when compared to cat-1, where
they are recently infected. 4 % (14) of Onychomycosis
and 2 % (7) of pityriasis versicolor were seen.
Prevalence of onychomycosis was equal in cat-1 and
cat-2, and no cases of pityriasis versicolor in cat-2.
Prevalence of onychomycosis was comparable to MunozPerez
et al. (1998) (4%) but CD4+ count was very low,
67cell/mm3 against their 161cell/mm3.
Mean CD4+ Count of pityriasis versicolor was 46cell/mm3.
Oral candidiasis accounted for 14 % (49), seen only in
cat-1, with mean CD4+ Count of 150.8.This prevalence was
lower than that reported by Sengupta et al. (2000)
-36%. Among 49 cases, 42 cases were pseudomembranous
type and 7 cases of erythematous type. Mean CD4+ Count
was 150.8cell/mm3.
Among
infestations, 7 cases of scabies were diagnosed in cat-1
and none in Cat- 2 that was comparable to Kumarasamy et
al. (2000) (0.5%).
Non-infectious lesions were present in 64 % (224) of the
study group in which the incidence in category 2 [68.75
% (154)] was significantly higher, when compared to
category 1 [31.25 %(70)]. When each lesion was
considered separately seborrhoeic dermatitis 14%
(42)
was the most common diagnosis, of which 29 % (14) were
in category 1 and 71 % (35) cases were in category 2 and
mean CD4+ count was 85.05cells/cu.mm. The prevalence was
bit high when compared to other studies such as Sen et
al. (2009) where the prevalence was 8.5%. This is
probably because their study was conducted in a more
mild and temperate climate. Rajagopalan, Jacob, and
George (1996) also showed increased prevalence compared
to our study. Hengge et al. (2000) reports decrease in
prevalence from 25.3% to 17.6% in patients who are
HAART. But a paradoxical increase was seen in
cat-2(under HAART) study group in our study.
Xerosis
was the next common [10 % (35)] diagnosis of which 40 %
(14) cases were in Cat-1 (non HAART) and 60% (21) in
cat-2. The mean CD4+ count was very low (35.75cells/mm3).The
prevalence in our study is low compared to that reported
by Sud et al. (2009) -22.7%. There was a bit high
prevalence in cat- 2 (HAART) when compared to cat-1 but
Maurer and Lori (2004) reports a decreased prevalence in
HAART initiated patients. And most of the patients were
cachexic.
Eosinophilic folliculitis was seen in 6 % (21) of study
population of which 66.7% (14)were in cat -1 (non HAART)
and 33.3% (7) were in cat-2(HAART). In our study mean
CD4+ count was 121.5cell/mm3, out of the 21
cases diagnosed, 14 cases fulfilled the criteria
[clinical, Histopathology and laboratory], but other
seven cases were diagnosed only on clinical grounds.This
was comparable to CD4 count of 115.54cells/cu.mm
reported by Priya et al. (2005)
Pruritic papular eruptions (PPE) were seen in 8 % (28)
of our patients, and all of them were from cat-2, with
mean CD4+ Count of 119.2cell/mm3. This is
comparable to Lakshmi et al. (2008) who report a
prevalence of between 11 and 46% with a mean CD4 count
of 153 cells/cu.mm. Also the CD4+ Count of 119.2cell/mm3
was comparable to Boonchai et al. (1999) where they
reports PPE as a marker of advanced HIV (low CD4+
count). To support this evidence, PPE was seen only in
cat-2 patients as these patients were on HAART owing to
their advanced HIV infection.
Drug
eruption was seen in 12% (42) of our patients. Nair,
Moorty, and Suprakasan (2003) (1.65%) reports very low
prevalence probable because their patients were in
initial stages of the disease against our population,
where it is seen only in cat-2 ,who were in advanced
stage of the infection .Of 12% (42), 8% (28) were
Nevirapine rash[ erythema multiforme and acneform
eruptions] and 4%(14) were Lichenoid eruptions. Mean
CD4+ Count was 92cell/mm3. This is
illustrated by Coopman et al. (1993) who have shown that
it is extremely common in HIV infected patients and
prevalence increases as the immune function
deteriorates.
One
case of pityriasis rosea was diagnosed in cat-1, but no
literature mentions it as an opportunistic infection
(OI). Some workers such as Robert A Allen, Robert
A Schwartz(2009) associates Human Herpes Virus -7(HHV-7)
as causative agent .Since herpes group of virus are
common opportunistic agents in HIV infection, this may
be a true association and further study is required in
this regard.
Conclusion
Oral Candidiasis was the leading presenting complaint
followed by Molluscum Contagiosum, Condyloma Accuminata
(seen only in male patients) and Multidermatomal Herpes
Zoster. So any patient with these symptoms can be
suspected as a case of HIV if other conditions are ruled
out.
In correlation with CD4 cell count mucocutaneous
manifestations increased with decreased CD4 cell count
[Regression Coefficient (-0.31) with 0.64 standard error
of estimate and p-value <0.05].
When dermatological lesions of patient who are on HAART
was compared with that of non-HAART, there was
significant reduction in the prevalence of
dermatological viral infection in CAT 2[under HAART-chi
square=5.134; p<0.023].But prevalence of bacterial and
fungal infections showed no change [p=0.763(NS) and
P=0.827(NS) respectively].This may be due to poor
socioeconomic status and poor hygiene. Since the study
mainly involved patients of lower socioeconomic status,
we suggest further studies be conducted by involving
patients of higher socioeconomic status matched for all
other criteria. However HAART improves the quality of
life in the HIV infected (Orlovic & Smego, 2009).
Abbreviations
Cat-1: (category-1) Patients directly presenting to skin
and Std. dept. without knowing their HIV status, i.e.,
not on HAART
Cat-2: (category-2) Patients on HAART.
HAART- Highly active antiretroviral therapy
NACO-National AIDS Control Organisation
CD4+ -Cluster of differentiation 4
KOH-Potassium Hydroxide mount
STD-Sexually transmitted disease
HIV- Human Immunodeficiency Virus
AIDS-Acquired Immunodeficiency Syndrome
VDRL- Venereal Disease Research Laboratory
ELISA- Enzyme Linked Immunosorbent Assay
VCTC-Voluntary Counselling and Testing Centre
OI- Opportunistic Infection
References
Attili VSS, Singh VP,
Sundar S, Gulati AK, Varma DK, Rai M. Relationship
between skin diseases and CD4 cell count in a hospital
based cohort of HIV infected adults in North India.
Journal, Indian Academy of Clinical Medicine (JIACM).
2008;9(1):20-5.
Bhandary PG, Kamath NK, Pai GS, Rao
G. Cutaneous manifestations of HIV infection. Indian
J Dermatol Venereol Leprol. 1997;63:35-7.
Boonchai W, Laohasrisakul R,
Manonukul J, Kulthanan K. Pruritic papular eruption in
HIV seropositive patients: a cutaneous marker for
immunosuppression. International Journal of
Dermatology. 1997; 38(5):348-350.
Bravo IM, Correnti M,
Escalona L, Perrone M, Brito A, Tovar V, et al.
Prevalence of oral lesions in HIV patients related to
CD4 cell count and viral load in a Venezuelan
population. Med Oral Patol Oral Cir Bucal.
2006;11:E1-5.
Coopman SA, Johnson
RA, Platt R, Stern R. Cutaneous disease and drug
reactions in HIV Infection. N Engl J Med
1993;328(23):1670-4.
Hengge UR, Franz B,
Goos M. Decline of infectious
skin manifestations in the era of highly active
antiretroviral therapy,
AIDS.
2000;14(8):1069.
HIV Estimates in India for the year 2006. NACO document;
http://www.naco.nic.in/indianscene/esthiv.htm.
Kumarasamy N, Solomon S, Madhivanan P, Ravikumar B,
Thyagrajan SP, Yesudian P. Dermatological manifestations
among human immunodeficiency virus patients in South
India. Int J Dermatol. 2000;39:192-5.
Maurer T, Rodrigues
LKE, Ameli N, Phanuphak N, Gange SJ, DeHovitz J, French
AL, Glesby M, Jordan C, Khalsa A, Hessol NA. The Effect
of Highly Active Antiretroviral Therapy on Dermatologic
Disease in a Longitudinal Study of HIV Type 1-Infected
Women. Clinical Infectious Diseases.
2004;38(4):579-584.
Mbuagbaw J, Eyong I,
Alemnji G, Mpoudi N, Same-Ekobo A. Patterns of skin
manifestations and their relationships with CD4 counts
among HIV/AIDS patients in Cameroon. Int J Dermatol.
2006;45:280-4.
Munoz-Perez
MA, Rodriguez-Pichardo A, Camacho
F, Colmenero MA. Dermatological findings correlated with
CD4 lymphocyte counts in a prospective 3 year study of
1161 patients with human immunodeficiency virus disease
predominantly acquired through intravenous drug abuse.
British Journal of Dermatology. 1998;139(1):33-39.
Nair SP, Moorty KP, Suprakasan S.
Clinico-epidemiological study of HIV patients in
Trivandrum. Indian J Dermatol Venerol Leprol.
2003;69:100-3.
Samet JH, Muz P,
Cabral P, Jhamb K, Suwanchinda A, Freedberg KA.
Dermatologic manifestations in HIV-infected patients: a
primary care perspective. Mayo Clin Proc.
1999;74(7):658-60.
Sen S, Halder S,
Mandal S, Pal PP, Halder A, Bhaumik P. Clinico-epidemiological
profile of cutaneous manifestations among human
immunodeficiency virus positive patients in the
sub-Himalayan region. Indian J Dermatol Venereol
Leprol. 2009;75:403-5.
Sengupta D, Rewari BB, Mishra SN, Joshi PL, Prasada Rao
JVR. Spectrum of opportunistic infections in AIDS:
Trends from India. JIACM. 2000;4:99-103.
Shobhana A, Guha SK,
Neogi DK. Mucocutaneous manifestations of HIV infection.
Indian J Dermatol Venereol Leprol. 2004;70:82-86.
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
Chhattisgarh, India. Indian J Dermatol.
2009;54(4):338-41.
Sud N, Shanker V,
Sharma A, Sharma NL, Gupta M. Mucocutaneous
manifestations in 150 HIV infected Indian patients and
their relationship with CD4 lymphocyte count.
International Journal of STD and AIDS.
2009;20:771-774.
Rajagopalan B, Jacob M, George S. Skin lesions in HIV
positive and negative patients in South India. Int J
Dermatol. 1996;35(7):489-92.
Lakshmi SJ, Raghurama
GR, Ramalakshmi, Satyashree, Rao KA, Prasad PG, Kumar
YHK. Pruritic papular eruptions of HIV: A
clinicopathologic and therapeutic study. Indian J
Dermatol Venereol Leprol. 2008;74(5):501-3.
Orlovic D, Smego RA.
Hypercoagulability Due to Protein S Deficiency in HIV-Seropositive
Patients. International Journal of Collaborative
Research on Internal Medicine & Public Health (IJCRIMPH),
2009;1(6&7):187-193.
Rajendran PM, Dolev
JC, Heaphy MR, Maurer T. Eosinophilic Folliculitis:
before and after the introduction of antiretroviral
therapy. Arch Dermatol. 2005;141(10):1227-1231.
UNAIDS update of the global HIV/AIDS Epidemic. December
2007. |
