Download Frequency of pulmonary tuberculosis in patients with skin diseases

Journal of Pakistan Association of Dermatologists 2013;23 (2):126-132.
Original Article
Frequency of pulmonary tuberculosis in patients
with skin diseases requiring high dose long-term
systemic steroid therapy
Ghazala Butt, Faria Asad, Khawar Khurshid, Zahida Rani, Sabrina Suhail Pal
Department of Dermatology, Unit II, King Edward Medical University/Mayo Hospital, Lahore
Abstract
Objective To determine the frequency of pulmonary tuberculosis in patients with skin diseases
requiring high dose long-term systemic steroid therapy.
Patients and methods This cross-sectional study was conducted in the Department of Dermatology
Unit-II, Mayo Hospital, Lahore. Newly diagnosed patients of skin disease were screened for
tuberculosis and then followed up after 6 weeks, 3 months and 6 months to evaluate pulmonary
tuberculosis while patients were on high dose systemic steroids. At each visit, history, examination
and screening tests for tuberculosis were performed which included sputum smear for acid-fast
bacilli (AFB), chest radiograph and sputum culture for AFB.
Results Out of fifty patients, who were on high dose long-term systemic steroid therapy, four
patients (8%) developed pulmonary tuberculosis after a period of three months (P=0.0001).
Conclusion Patients on high dose long-term systemic steroid therapy can develop pulmonary
tuberculosis.
Key words
Frequency, tuberculosis, steroids.
Introduction
Tuberculosis is a chronic and serious infection,
if left untreated. It is caused by the acid-fast
bacillus, Mycobacterium tuberculosis. The
disease affects various systems of the body
including
lungs,
gastrointestinal
tract,
genitourinary system, skin, bones, joints,
lymphoreticular and central nervous systems.1
A patient suffering from active tuberculosis
infects 10 to 15 persons every year.2 People
Address for correspondence
Dr. Ghazala Butt
Department of Dermatology, Unit II
King Edward Medical University/Mayo
Hospital, Lahore
Ph# 03334306199
Email: [email protected]
carrying tubercle bacilli in their body do not
necessarily present with the signs and symptoms
of tuberculosis because the immune system
walls off the causative organism and keeps it
dormant for years. When someone’s immune
system is compromised, the chances of
tuberculosis to become active are greater. Every
second a new person is infected with the
tubercle bacilli. Currently, one third of the world
population is infected with this bacillus.2 Five to
ten percent of immunocompetent world
population suffers from tuberculosis during their
life span.2 In Pakistan, the prevalence of
tuberculosis (including HIV) was 355 per
100,000 populations in the year 2009.3
There is a greater risk of acquiring tuberculosis
in immunocompromised individuals e.g. AIDS
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Journal of Pakistan Association of Dermatologists 2013;23 (2):126-132.
patients and those on immunosuppressive
therapy.4 Tuberculosis in an immunosuppressed
person may arise from primary infection, by
reactivation and/or reinfection.5
In dermatology, systemic glucocorticoids are the
mainstay of immunosuppressive therapy for
immunobullous diseases and collagen vascular
disorders.
Prolonged
and
high
dose
administration of glucocorticoids is often needed
to control certain diseases such as pemphigus,
bullous pemphigoid, lupus erythematosus and
dermatomyositis. Such patients are at risk for
both the acquisition of primary tuberculosis and
the reactivation of non-active tuberculosis. The
immunosuppression due to glucocorticoids in
such patients not only masks the symptoms and
signs of tuberculosis leading to a delay in
diagnosis but also predisposes the patients to
more severe variants of the disease, e.g.
disseminated tuberculosis.6
At each visit (Figure 1), sputum smear for acidfast bacilli (AFB) was done for three
consecutive days. No further test was performed
if two or more sputum smears were positive for
AFB.
If only one sputum smear was positive for AFB,
then X-ray chest was carried out to detect any
abnormalities that were consistent with active
pulmonary tuberculosis. If positive, no further
test was performed. If one sputum smear was
positive for AFB and X-ray chest findings were
not supportive of pulmonary tuberculosis then
sputum culture was carried out. If positive, the
patient was diagnosed as a case of pulmonary
tuberculosis.
If sputum smear for AFB was negative for three
consecutive days then sputum culture was
carried out. If one or more sputum cultures were
positive, patient was diagnosed as a case of
pulmonary tuberculosis.
Patients and methods
Patients presenting in dermatology department
Mayo Hospital, Lahore and fulfilling the
inclusion criteria (patient of either sex,
belonging to adult (≥12 years) age group,
requiring high dose long-term systemic steroid
therapy for their skin problem, were enrolled.
Patients currently on antituberculous therapy
(ATT), systemic steroid therapy, any other
immunosuppressive
therapy
and
with
uncontrolled diabetes were excluded from the
study. After getting informed consent,
demographic data were obtained. History was
taken; clinical examination and screening tests
were performed on first visit. Patients were
followed after six weeks, three months and
finally at six months to evaluate them for
pulmonary tuberculosis.
If sputum smear for AFB was negative for three
consecutive days and sputum culture was also
negative, then patient was labelled as a case of
pulmonary tuberculosis if at least two series of
smears from samples taken at least two weeks
apart were negative, and persistent radiographic
abnormalities
compatible
with
active
tuberculosis which did not improve with
treatment using broad spectrum antibiotics for at
least one week.
A pro forma was used to record the history,
physical examination and the results of
screening tests. Collected information was
transferred to SPSS (Statistical Package for the
Social Sciences) version 19 computer software
program and was analyzed accordingly. Mean,
median and standard deviation were used to
represent the quantitative variables. McNemar
test was applied to calculate the P value.
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Journal of Pakistan Association of Dermatologists 2013;23 (2):126-132.
Sputum smear for acid-fast
bacilli for 3 consecutive days
≥2 sputum smear positive
If 3 consecutive sputum
smears negative
If one sputum smear positive
X-ray chest
Sputum culture
If supportive
If not supportive
If positive
If negative
Sputum culture
If positive
CASE OF
TUBERCULOSIS
Two series of negative
smears from samples
taken two weeks a part
+ X-ray chest
supportive of active TB
not improved with
antibiotics for one week
Figure 1 Algorithm for diagnosis of pulmonary tuberculosis (followed at each visit).
Results
In this study, fifty patients suffering from skin
diseases requiring long-term high dose systemic
steroid therapy were enrolled. There were 24
male and 26 female patients. The age range of
patients was 15-75 years with a mean age of 39
years.
Most of the patients were suffering from
pemphigus vulgaris (n=37), while five patients
were of systemic lupus erythematosus. Patients
with other skin diseases are shown in Table 1.
Table 1 Frequency of different skin diseases
requiring long-term high dose steroid therapy (n=50).
Dermatoses
N (%)
Pemphigus vulgaris
37 (74)
Systemic lupus erythematosus
5 (10)
Pemphigus foliaceus
3 (6)
Bullous pemphigoid
3 (6)
Lupus erythematosus/lichen planus 2 (4)
This study concluded that 4 patients (8%)
suffering from pemphigus vulgaris, who were on
high dose long-term systemic steroid therapy,
developed pulmonary tuberculosis after a period
of three months. Out of these 4, 1 was female
and 3 were male patients. At six week’s
evaluation, 2 patients showed abnormal chest Xray findings but sputum smear and culture for
AFB were negative at that time. At 3 months
follow-up, in addition to the above 2 patients, 2
more patients developed chest X-ray
abnormalities and in these again sputum smear
and culture for AFB were negative (Figure 2).
All these patients were given broad spectrum
antibiotics for two weeks in addition to high
dose systemic steroid therapy, but their X-ray
chest findings did not resolve. At that time
sputum smear and culture were performed which
turned out to be positive and patients were put
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Journal of Pakistan Association of Dermatologists 2013;23 (2):126-132.
Figure 2 Positive sputum smear and culture for acid-fast bacilli and X-ray chest findings in study population (n=50),
[P=0.0001].
on ATT. One patient at 6 months follow-up
developed X-ray chest abnormalities and was
given antibiotics for 2 weeks and his
radiological chest findings resolved.
Out of 4 patients who developed pulmonary
tuberculosis, 3 were male and one female. One
male patient was labourer and 2 were
unemployed. All patients were married. The
female was a housewife. All these 4 patients
belonged to poor socioeconomic class. Two
male patients were smokers. Three patients were
underweight and one was of normal BMI.
Family history of pulmonary tuberculosis was
present in two patients. History of BCG
vaccination was present in all 4 patients. ESR
was also high in all patients.
Discussion
Research on the role of steroid therapy in
precipitating
tuberculosis
is
limited.7
Aggravation of infections is a known side effect
of steroids.7 Some maintain that steroid therapy
might cause exacerbation of active or apparently
inactive tuberculosis while others conclude that
steroid treatment has negligible influence on the
incidence of tuberculosis.8
In this study, we found statistically significant
(P<0.05) association between prednisolone
dosage i.e. more than 1 mg/kg daily for six
months and development of pulmonary
tuberculosis. Studies from different parts of the
world also support our findings. Kim et al.9
reported an increase in the incidence of active
tuberculosis among 269 patients of rheumatic
disease on moderate to high doses of
corticosteroids. The risk factors were,
cumulative and mean daily steroid doses taken
during the first year of therapy. Sasaki et al.10
found that the mean length of time from start of
corticosteroids, with the dose that ranged
between 13.9 mg to 20 mg, to the occurrence of
tuberculosis was 4.1 years in most of his patients
suffering from collagen vascular disease.
Kobashi et al.11 found five patients among a total
of 162 (3.1%) who developed pulmonary
tuberculosis on long-term corticosteroid therapy.
The total corticosteroids consumed, until the
clinical diagnosis of pulmonary tuberculosis
were 1.16 gms to 5.6gms, lasting two to nine
and a half months. Dryga et al.12 found 39 cases
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Journal of Pakistan Association of Dermatologists 2013;23 (2):126-132.
of progressive tuberculosis among those on
glucocorticoid treatment with different doses.
Jick et al.13 found that patients treated with
glucocorticoids have an increased risk of
developing tuberculosis independent of other
risk factors. Chan and Yosipovitch6 carried out
screening of tuberculosis in patients taking oral
glucocorticoids and they found that lower or
intermittent doses of glucocorticoids are not
associated with tuberculosis. Sayarlioglu et al.7
determined that high doses of prednisolone were
important determinant for increased risk of
tuberculosis in patients with SLE. Pal et al.8 also
concluded that systemic steroid therapy over
long periods causes significant increase in the
incidence of tuberculosis.
There are many mechanisms by which
glucocorticoids can increase the risk of
tuberculosis. Corticosteroids, through their
immunosuppressive
and
antiinflammatory
effects, impair antibody formation and cellmediated immunity that tuberculosis requires for
its control.13 Glucocorticoids inhibit the
lymphokine effect and monocyte chemotaxis
and also block Fc receptor binding and
function.13 Glucocorticoids depress the number
of peripheral blood monocytes as well as
monocyte functions, including bactericidal
activity and production of interleukin-1 and
TNF-α. Glucocorticoids also inhibit T cell
activation, leading to reduced proliferative
responses and cytokine production, and they also
induce a redistribution of lymphocytes
(predominantly T-cells) out of the circulation,
leading to peripheral lymphocytopenia.13 These
various effects of glucocorticoids on the cellular
immune system may play a significant role in
predisposing to tuberculosis infection. These
effects are most evident if steroid doses exceed
0.03mg/kg/day of prednisolone or equivalent. At
doses higher than 1 mg/kg/day, a marked
increase in susceptibility to a wide variety of
infections is experienced after several weeks.
Treatment for less than 5 days appears to have
less effect on immune function and
predisposition to infections. Continuous therapy
has
longer
and
more
profound
immunosuppressive effects as compared to
intermittent therapy.8
Smoking can be an important modifiable risk
factor for tuberculosis in developing countries.
We found that 2 of the patients who developed
pulmonary tuberculosis were smokers. A
substantially stronger association exists between
smoking and tuberculosis. The impact of
smoking on the potential conversion of latent
infection into active disease is higher in the
countries with high tuberculosis prevalence. An
Indian study14 showed that individuals who had
ever smoked were 3 times more likely to
develop tuberculosis than individuals who had
never smoked. Similarly, tuberculosis deaths
among those who had ever smoked were 4 times
higher than non-smokers. Iron loading in the
bronchoalveolar macrophages, secondary to
tobacco smoking, has been implicated in
promoting the growth of M. tuberculosis, thus
potentially contributing to the disease
manifestation and progress.13
In our study, all the four patients belonged to
poor socioeconomic class. There is a very strong
correlation between poverty and tuberculosis. It
is likely that poor housing in terms of crowding
leads to increased transmission and poor
nutrition leading to diminished immunity.15
The association of tuberculosis with body build
has been well reviewed. Lean underweight
people have a significantly higher risk of
developing tuberculosis than persons of or above
ideal body weight.15 Three of our patients who
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Journal of Pakistan Association of Dermatologists 2013;23 (2):126-132.
developed pulmonary tuberculosis were
underweight and one was of normal BMI.
In our study, all the 4 patients gave the history of
BCG vaccination. In terms of risk for
tuberculosis, infants and teenagers who have had
BCG vaccination are probably at reduced risk of
developing tuberculosis by about 75% for no
more than 15 years.15 Some trials have shown
that BCG vaccine is 80% protective and in
others it is 20%.15 Because of variation in trial
results, most countries give BCG vaccine at
birth to provide protection in the early years
when infection can often lead to devastating
widespread disease such as miliary tuberculosis
or tuberculous meningitis. This is particularly
important in high prevalence countries where the
chance of being infected in very early life is
high.15
Patients with skin diseases requiring high dose
long-term systemic steroid therapy should be
screened for pulmonary tuberculosis before and
at intervals of three months after commencement
of systemic steroids and provided with
appropriate treatment if it is detected. Failure to
do so may result in reactivation of tuberculosis
and subsequent dissemination of the disease.
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The importance of establishing an association
between high dose, long-term systemic steroid
therapy and development of pulmonary
tuberculosis is that tuberculosis is a contagious
and a common disease in Pakistan. High dose
long-term systemic steroid therapy causes
immunosuppression and masking of symptoms
and signs of tuberculosis causing a delay in
diagnosis and also primary infection, reinfection and reactivation of non-active
tuberculosis. By screening for tuberculosis in
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