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Confirmed CoExistence

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Confirmed CoExistence

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Mise et al.

Cases Journal 2010, 3:24


http://www.casesjournal.com/content/3/1/24

CASE REPORT Open Access

A rare case of pulmonary tuberculosis with


simultaneous pulmonary and skin sarcoidosis: a
case report
Kornelija Mise1, Ivana Goic-Barisic2*, Neira Puizina-Ivic3, Igor Barisic4, Marija Tonkic2, Irena Peric1

Abstract
Background: Tuberculosis and sarcoidosis are chronic diseases that rarely occur concomitantly. Sarcoidosis is a
multisystem granulomatous disorder characterized pathologically by the presence of non-caseating granulomas in
involved tissues. Tuberculosis is infectious disease caused by Mycobacterium tuberculosis characterized by
granulomas with caseous necrosis.
Case presentation: We present a case of 43-year-old female refugee from Kosovo with microbiological
confirmation of pulmonary tuberculosis and pulmonary and skin sarcoidosis at the same time. Three weeks after
corticosteroid therapy for pulmonary sarcoidosis was introduced, positive finding of mycobacterium culture of
bronchial aspirate was observed. Based on these results, corticosteroid therapy was excluded and antituberculous
therapy was introduced for six months. In the meantime, new nodes on face and nose appeared and skin
sarcoidosis was diagnosed. The patient was given corticosteroids and colchicine according to the skin and
pulmonary sarcoidosis therapy recommendation.
Conclusion: The authors of this study suggest that in cases when there is a dilemma in diagnosis between
tuberculosis and sarcoidosis we should advance with corticosteroid therapy until we have microbiological
confirmation of mycobacterium culture. This case is remarkable because this is a third described case of sarcoidosis
and tuberculosis together (the first reported in Asia, the second in South Africa), and to authors knowledge, this is
a first case report in Europe.

Background finding) has stimulated the search for an association


Tuberculosis and sarcoidosis are chronic granulomatous between mycobacterium and sarcoidosis, and it has been
diseases. In many aspects, they are similar although dif- hypothesized that sarcoidosis could be a separate mani-
ferent. Tuberculosis is infectious disease caused by festation of infection with mycobacterium [2]. These dis-
Mycobacterium tuberculosis (MTB) characterized by eases occur concomitantly very rarely [4,5]. Less
granulomas with caseous necrosis, and the treatment is commonly, tuberculosis develops as an opportunistic
focused on elimination of microorganism. Sarcoidosis is infection in patients following corticosteroid treatment
systemic disease of unknown etiology, and is character- for sarcoidosis.
ized by noncaseous granulomas, therefore it cannot be
treated etiologically but immunosuppressive as a sys- Case presentation
temic immunological disease [1,2]. Overall mortality In this very rare case of 43 years-old female, refugee
from sarcoidosis is 1-5% usually from respiratory, car- from Kosovo, was admitted as an outpatient to the
diac or central nervous system disease [3]. The histolo- Department of pulmonary diseases in 2003. because of
gical similarity between sarcoidosis and tuberculosis erythema nodosum and dry cough. She was without
(with epithelioid cell granulomas as the typical common fever during admission, smoked up to 30 cigarettes daily
and was healthy most of her life. She suffered only of
* Correspondence: ivanagoicbar@net.hr
2
head injury and face trauma acquired during the war
Department of Clinical Microbiology and School of Medicine University of
Split, Split, Croatia
(during 1995.) by shelling. Three years before the

© 2010 Mise et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Mise et al. Cases Journal 2010, 3:24 Page 2 of 5
http://www.casesjournal.com/content/3/1/24

outbreak of erythema nodosum, two small red subcuta- usual scheme for lung sarcoidosis, prednisolone 1 mg/kg
neous tubercles were found on her forehead, in the left body weight. Three weeks after introducing corticoster-
eyebrow area. The biopsy test showed chronic granulo- oid therapy, culturing the sample on Lowenstein-Jensen
matous infection that was described as a reaction to a solid medium by using liquid culture method MGIT
foreign body. (Mycobacterium Growth Indicator Tube), Mycobacter-
Laboratory analysis revealed ESR 37 (normal range 0- ium tuberculosis was isolated. The sensitivity test was
15 mm/h), WBC 9.030/mm3, RBC 3,7/mm3 and C-reac- performed by using the proportion method on solid
tive protein 9.8 mg/L, AST 60 U/L, ALT 76 U/L, GGT Lowenstein-Jansen culture according to CLSI (Clinical
86 U/L, AP 79 U/L, while urea, creatinine, calcium in and Laboratory Standards Institute) standards. All the
serum and 24 hours urine were within normal range. four routine tested antituberculotics (isoniazid, rifampi-
Angiotensin-converting enzyme (ACE) was elevated 108 cin, ethambutol and streptomycin) responded well to
U/l (normal 0-56). Tuberculosis test (2 IU) was 14 mm sensitivity test and the susceptibility of pyrasinamide
of induration in diameter. The result of spirometry mea- was confirmed in the referral national laboratory. A pre-
sured 85% vital capacity (VC), 94,5% of forced vital vious diagnosis was corrected to microbiological con-
capacity (FCV), 77% of forced expiratory volume firmed lung tuberculosis. Corticosteroid therapy was
(FEV),82,4% of forced expiratory volume in first second excluded after three weeks of treatment and antituber-
(FEV1) and FEV1/FCV 87,2% from referral values. Arter- culotic therapy (ATL) was introduced. The patient was
ial blood gases were pO2 9,8 kPa, pH 7.45 and diffusing treated with rifampicin 600 mg, isoniazid 400 mg, etam-
capacity of carbon monoxide (DLCO) 72%. Chest radio- buthol 1200 mg and pyrazinamide 1500 mg, on a daily
gram showed fibroindurative changes in the area of basis during two months, after pyrazinamide was
both upper lobes with lung traction. In upper lobes sub- excluded and triple therapy was continued for one
pleurally and more to the left there was a focus with month. After three months from the beginning of ATL
«round glass» pattern. Mycronodular interstitial infiltra- treatment, ethambuthol was excluded and rifampicin
tions were found bilateral on chest radiogram with and isoniazid were continued for the next 3,5 months
fibrous changes of hilus (Figure 1). High-resolution (entirely 6,5 months) with controlling regular hematolo-
computed tomography (HRCT) of thorax showed inter- gical and biochemical analysis. The patient was in good
lobar and peribronchial thickness in upper lung lobes clinical condition. However, ACE was continuously
with subpleural fibroses and deformation of bronchi. raised, 80-100 U/l. After four months of ATL therapy
There were minor areas of fresh infiltrations in apices chest radiogram was made showing complete regression
on both sides, suggesting a new pathological process. of tiny infiltrates in both upper lobes and small regres-
There was a cavity 8 × 12 mm large in apical-posterior sion of nodular infiltrates which was described as unsa-
segment of the upper left lobe. Hilar lymph nodes were tisfactory. During ATL therapy new nodes on face and
more then 2 cm in diameter, some of them had fibrous nose, similar to those on the forehead appeared (Figure
changes and some were calcificated. High resolution 4). The biopsy of skin changes was made and the patho-
thorax CT with hilar lymph nodes enlargement and histological confirmation for sarcoidosis is evident on
granulomas with reticular interstitial pattern in the the Figure 5. Antituberculotic therapy was preceded for
lower respiratory part is present on the Figure 2(a, b). next two months until negative mycobacterium culture
Fiberbronchoscopy revealed slightly edematous and in new collected sputum was obtained. In course of the
hyperemic mucous membrane of bronchi on both sides, last month of TB therapy novel bigger, firm nodes
while purulent secrete was seen in bronchus left upper appeared on ear lap. Pathohistological tests indicate sar-
lobe and in lingul. The routine bacteriological culture of coidosis of the skin.
bronchial aspirate was sterile. Direct smear microscopy Microbiological examinations of the skin substrata in
examination of the sample for the presence of acid- direct microscopy and polymerase chain reaction (PCR)
resistant bacilli by using Ziehl-Neelsen method was with specific primer had not confirmed presence of M.
negative. Pathohistological findings of lung (Figure 3) tuberculosis. After 6 months of the beginning of ATL
and bronchial walls biopsy showed chronic granuloma- treatment, the patient received corticosteroid (predniso-
tous infection without caseous necroses. In bronchoal- lone 40 mg daily) and colchicine therapy (200 mg daily)
veolar lavage (BAL) CD4+ lymphocytes and alveolar for lung and skin type of sarcoidosis. After four months
macrophages were predominantly. The ratio of CD4+ of the corticosteroid therapy chest radiogram showed
and CD8+ lymphocytes was 5.5:1. All relative findings, almost complete regression of nodular infiltrates in lung
including pathohistological examination indicate lung parenchyma. The skin changes were considerably smal-
sarcoidosis. The patient was stared corticosteroid ther- ler, dry on surface, and there were no new lesions on
apy (out of hospital-out-hospital patient) according to the skin while ACE was in normal rate (30 U/l).
Mise et al. Cases Journal 2010, 3:24 Page 3 of 5
http://www.casesjournal.com/content/3/1/24

Figure 3 Pathohistological findings of lung and bronchial walls


biopsy showed chronic granuloma infection without caseotin
necrosis, characteristic for sarcoidosis.
Figure 1 Chest radiogram with fibroproductive changes in the
area of both upper lobes and mycronodular interstitial
infiltration bilateral. can be positive in the cases of sarcoidosis. Recent inno-
vative blood tests that measure the cell-mediated
immune response of TB-infected individuals like quanti-
Discussion feron test are highly specific for detecting M. tuberculo-
A rare case of skin and lung sarcoidosis with positive sis infection and may be helpful in diagnostic
mycobacterium culture obtained from bronchial aspirate evaluations in conjuction with risk assessment and
has been presented. Sarcoidosis is a common multisys- radiography [6]. At the time of patient admission, we
tem granulomatous disease that frequently involves the did not use quantiferon-TB Gold test yet.
lungs and can result in pulmonary fibrosis [2]. Based on
positive finding of the bronchial aspirate, the diagnosis In the last 20 years, the research papers have
of lung TB was confirmed. According to authors’ knowl- recorded detection of mycobacterial DNA in some
edge there has not been described a case with positive sarcoide lesions, especially in lymph nodes that indi-
culture on MTB obtained from bronchial aspirate and cates possible connection between these two diseases
with noncaseous granulomas in lung parenchyma, bron- [7-11]. Silent asymptomatic stage I of sarcoidosis
chial wall and skin. Pathohistological findings of lung complicated with pulmonary tuberculosis has been
and bronchial wall suggested on sarcoidosis, but confus- recent published [12].
ing fact was positive tuberculosis skin test, although it

Figure 2 Thorax CT with hilar lymph nodes enlargement (a) and reticular interstitial pattern with granulomas of both lower lobus (b).
Mise et al. Cases Journal 2010, 3:24 Page 4 of 5
http://www.casesjournal.com/content/3/1/24

Figure 5 Pathohistological evidence of noncaseating


granulomas in skin biopsy, characteristic for sarcoidosis.

often during the war in Croatia (1991.-1995.) and


another parts of former Yugoslavia, because of the
migration of the population from other parts of the Bal-
kan (refugees, fugitives from Bosnia and Kosovo) where
the incidence of lung tuberculosis was very high, com-
paring to Croatia (Kosovo 80/100000, Southern Croatia
18-20/100 000).
In the Sothern Croatia ratio of tuberculosis and sar-
Figure 4 Multiple new nodes on face during ATL therapy
pathohistological verified as sarcoide granulomas.
coidosis is 1:10 [16]. During ATL therapy complete
regressions of new infiltrates in the upper lobe without
mycronodular infiltrates has been achieved. Skin sarcoi-
dosis was pathohistological confirmed, with negative
Sarcoidosis may presents with a wide range of symp- direct smear microscopy examination in Ziehl-Neelsen
toms. Noncaseating epitheloid cell granulomas charac- stain and absence of mycobacterium DNA in skin
terizing sarcoidosis may affect most organs, including granulomas.
the skin. Skin lesions may be the only manifestations, or Absence of mycronodular infiltrates (granulomas) in
just one of several other organ involvements. Cutaneous lung parenchyma and reduced changes of skin during 4
lesions are present in ~25% of sarcoidosis patients [13]. months of corticosteroid therapy have additionally
The skin lesions could have specific aspects (papules, proved the diagnosis of sarcoidosis with M. tuberculosis
plaques, nodules, alopecia or purple scars) or can be positive lung tuberculosis. Three years before sarciodosis
more or less nonspecific (erythema nodosum) [14]. In and tuberculosis had been diagnosed, skin forehead
the Netherlands epidemiological study sarcoidosis was granuloma was verified which was explained as granu-
mostly associated with rheumatoid arthritis [15]. loma of a foreign body due to previous injuries at shel-
The presented case has been of clinical interest ling. However, according to this study, skin sarcoidosis
because it happens very rarely that pulmonary tubercu- cannot be excluded at that time. If the bronchial aspi-
losis and lung sarcoidosis coincide in the same patient rate had not been sent for microbiological testing and if
with noncaseous lung granulomas. The dilemma was the therapy with corticosteroid had continued, a severe
present only because Mantoux test (skin test) was posi- type of lung TB with cavities and probably galloping
tive. In the former states of Yugoslavia tuberculosis skin tuberculosis would have been developed. This particular
test was positive in more than 95% of population represented case suggests us if suspicion of tuberculosis
because bacillus Calmette-Guerin vaccination (BCG vac- is high (for example when the patient had a tuberculin
cine) was compulsory. It had to be carried out just after test of 14 mm, a cavity 8 × 12 mm in the apical-poster-
birth and then three times until a person was 18 years ior segment of the upper left lobe and purulent secre-
old. In spite of vaccination, inhabitants can come in tion from the left upper lobe bronchus on
touch with the infected persons, and it happened more bronchoscopy) the ATL treatment can start
Mise et al. Cases Journal 2010, 3:24 Page 5 of 5
http://www.casesjournal.com/content/3/1/24

immediately. In the cases when patient’s condition is substantial intellectual content. MT and IP provided data read and approved
the manuscript. All aurhors read and approved the final manuscript.
rapidly deteriorating, corticosteroids and antituberculo-
sis therapy could be started concurrently, until micro- Competing interests
biological confirmation is established. The authors declare that they have no competing interests.
In cases when there is a dilemma in diagnosis between Received: 6 November 2009
tuberculosis and sarcoidosis, we should advance with Accepted: 13 January 2010 Published: 13 January 2010
corticosteroid therapy until we have microbiological
confirmation of mycobacterium culture [17]. In this par- References
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Author details Sarcoidosis Vasc Diffuse Dis 2001, 18:60.
1
Department of Pulmonary Diseases and School of Medicine University of 17. Paramonthayan S, Lasserson T: Treatments for pulmonary sarcoidosis.
Split, Split, Croatia. 2Department of Clinical Microbiology and School of Respir Med 2008, 102:1-9.
Medicine University of Split, Split, Croatia. 3Department of Dermatology
Diseases and School of Medicine University of Split, Split, Croatia. doi:10.1186/1757-1626-3-24
4
Department of Diagnostic and Interventional Radiology and School of Cite this article as: Mise et al.: A rare case of pulmonary tuberculosis
Medicine University of Split, Split University Hospital, 21000, Split, Croatia. with simultaneous pulmonary and skin sarcoidosis: a case report. Cases
Journal 2010 3:24.
Authors’ contributions
KM conceived the study and participated in patient management, treated
the patient and collected written informed consent. IGB participated in
acquisition of data, interpretation of data and was major contributor in
writing the manuscript. NPI and IB revised critically the manuscript adding

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