Case report

BMJ Case Rep: first published as 10.1136/bcr-2022-254392 on 15 May 2023. Downloaded from http://casereports.bmj.com/ on November 5, 2024 at Franklin Square Hospital Health
Disseminated tuberculosis involving the eye, skin,
axillary lymph nodes and lungs in an
immunocompetent host
Obaid Imtiyazul Haque ‍ ‍,1 Syed Asghar Rizvi,2 Ziya Siddiqui2

1
Massachusetts General SUMMARY peripheral hyperpigmentation and central ulcer-
Hospital, Harvard Medical A female in her early 40s presented to the outpatient ation in the left gluteal region (figure 1B).
School, Boston, Massachusetts, clinic for weight loss, fatigue, cough, followed by a
USA
2 gradual painful loss of vision in the right eye associated INVESTIGATIONS
Jawaharlal Nehru Medical
College and Hospital, Aligarh,
with redness over the past 3 months. Physical Haematological tests
Uttar Pradesh, India examination revealed bilateral axillary lymphadenopathy The haematology results were notable for mildly
and non-­healing skin ulcers on the left forearm and the elevated inflammatory parameters—leucocytosis,
Correspondence to left gluteal region. The patient had no light perception elevated C reactive protein and erythrocyte sedi-
Dr Obaid Imtiyazul Haque; in the right eye and grade 4+ cells in the anterior mentation rate along with mild normocytic and
​oihaque@​myamu.​ac.​in chamber. A chest X-­ray showed a cavitary lesion in normochromic anaemia. The laboratory findings
the left upper lobe. Histopathological tests from the are summarised in table 1.
Accepted 3 May 2023 skin and lymph nodes revealed caseating granulomas,
raising the suspicion of tuberculosis. A sputum nucleic
acid amplification test was performed, which returned Ocular investigations

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positive for Mycobacterium tuberculosis. The patient was She had no light perception in the right eye and
treated with antitubercular chemotherapy and showed 6/9 visual acuity in the left eye. Slit-­lamp examina-
encouraging signs of progress after the treatment. tion of the anterior segment revealed circumcorneal
congestion, hazy cornea due to corneal oedema,
hyphema involving almost half of the anterior
chamber (grade II) and extensive neovascularisation
BACKGROUND of the iris (figure 2A), corneal oedema and keratic
Tuberculosis (TB) is the most common infection precipitates (figure 2B,C). The left eye was unre-
in humans worldwide. The Centers for Disease markable on a slit-­lamp examination. Intraocular
Control and Prevention estimates that in 2018, pressures on Goldmann applanation tonometry
1.7 billion people were infected by TB—roughly were 7 mm Hg and 17 mm Hg in the right eye and
23% of the world’s population. TB claims the lives the left eye, respectively. The fundus examination
of 1.5 million people annually, making it the leading of the left eye was unremarkable but could not be
infectious disease killer in the world.1 Although the done in the right due to media opacities. B-­scan
lungs are commonly affected by TB, it can affect ultrasonography demonstrated choroidal mass with
any organ in the body. In this report, we describe a high internal reflectivity, mild vitreous haemor-
case of a woman in her early 40s with disseminated rhage and exudative retinal detachment in the right
TB involving the eye, skin, lungs and axillary lymph eye (figure 3A,B).
nodes.
Imaging
CASE PRESENTATION Chest X-­ray showed a cavitary lesion in the left
A female in her early 40s presented to the outpa- upper lobe (figure 4). Ultrasonography of the
tient clinic with complaints of recent onset of axillary region showed multiple conglomerated
weight loss, fatigue, cough and gradual painful loss lymph nodes bilaterally, with the largest measuring
of vision in the right eye associated with redness. 3×1.3 cm in the left axilla (figure 5).
She had a preceding history of chronic cough, peri-
odic fever and night sweats. The patient did not Histopathological and microbiological tests
seek a medical opinion and took over-­the-­counter A fine-­needle aspiration (FNA) biopsy was obtained
pain medications and eye drops for 6 weeks prior from the largest axillary lymph nodes bilaterally
to the presentation. The vital signs (pulse, blood under ultrasonographic guidance, revealing pus
© BMJ Publishing Group
Limited 2023. No commercial
pressure, respiratory rate and body temperature) and caseum-­like exudate. A biopsy from the skin
re-­use. See rights and were unremarkable. Physical examination revealed lesion was obtained, and all samples were sent for
permissions. Published by BMJ. a palpable and non-­tender, firm, bilateral axillary pathological and microbiological examination. The
lymphadenopathy. She was also noted to have a axillary lymph node biopsy showed epithelioid
To cite: Haque OI, Rizvi SA,
Siddiqui Z. BMJ Case well-­demarcated (3×3 cm) skin lesion with palpable granulomas with central necrosis and multinucle-
Rep 2023;16:e254392. peripheral erythematous nodules and central ated giant cells of Langhans; the smear was negative
doi:10.1136/bcr-2022- ulceration on the medial aspect of the left elbow for acid-­fast bacillus (figure 6A). Histopatholog-
254392 (figure 1A) and another skin lesion (5×2 cm) with ical examination of the skin biopsy revealed the
Haque OI, et al. BMJ Case Rep 2023;16:e254392. doi:10.1136/bcr-2022-254392 1
Case report

BMJ Case Rep: first published as 10.1136/bcr-2022-254392 on 15 May 2023. Downloaded from http://casereports.bmj.com/ on November 5, 2024 at Franklin Square Hospital Health
Figure 1 (A) A 3×3 cm plaque with peripheral erythematous nodules
and central ulceration on the medial aspect of the left elbow and
(B) a 5×2 cm plaque with peripheral hyperpigmentation and central
ulceration in the left gluteal region.

caseating granulomas in the dermis (figure 6B). Syphilis and HIV

serology results were negative.
The histopathological results raised the suspicion of TB, and
the sputum cartridge-­based nucleic acid amplification test (CB-­
NAAT) was performed, which returned positive for Mycobac-
terium tuberculosis sensitive to rifampin. Based on her history,
physical examination and investigation results, we made the Figure 2 Slit-­lamp image of the anterior segment of the patient’s
diagnosis of disseminated TB involving the right eye, skin (lupus right eye showing (A) circumcorneal congestion, hazy and oedematous

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vulgaris), axillary lymph nodes and lungs. cornea, hyphema involving half of the anterior chamber, and
neovascularisation of iris on diffuse illumination, (B) corneal cross-­
DIFFERENTIAL DIAGNOSIS section view showing corneal oedema and keratic precipitates, and
The initial clinical evaluation of weight loss, bilateral axillary (C) a short beam of light shone at 45° angle through the limbal sclera
lymphadenopathy and choroidal mass in the right eye raised (sclerotic scatter) highlights the diffuse deposition of keratic precipitates
suspicion of metastatic cancer possibly originating from the on the endothelial surface.
breasts. However, after a thorough breast examination, ultraso-
nography of breasts and screening mammogram returned nega- to reduce the inflammation and prevent the right eye from
tive, breast cancer was ruled out. progressing to phthisis bulbi.

TREATMENT OUTCOME AND FOLLOW-UP

The patient was started on a four drug antituberculous chemo- On the first follow-­up, 1 week after the initial presentation, she
therapy (rifampin, isoniazid, pyrazinamide and ethambutol) was stable and had no additional complaints. Her sputum tested
for 2 months followed by three drugs (rifampin, isoniazid and negative for M. tuberculosis 2 months after the initiation of treat-
ethambutol) for another 4 months. She was also prescribed ment. After 2 months of chemotherapy, the cutaneous lesions
mandatory protective eyeglasses to protect her healthy left eye. began disappearing, and symptoms of fatigue and night sweats
The baseline vision was closely monitored in the healthy eye for resolved during the same period. Lymphadenopathy resolved by
signs of ethambutol-­induced optic neuropathy. Topical eye drops the fifth month of treatment.
containing prednisone acetate and atropine were prescribed
DISCUSSION
TB is a multisystem disease caused by M. tuberculosis, commonly
Table 1 Results of haematological tests contracted through inhaling droplets containing the bacteria.
Investigations Results Despite the development of vaccine and anti-­tuberculous drugs,
Haemoglobin 10.2 mg%
Mean corpuscular volume 82 fL
Mean corpuscular haemoglobin concentration 345 g/L
Total leucocyte count 11 500/µL
Differential leucocyte count P 72.1% M 4.0% L 23.9%
Red blood cell (RBC) count 4×106/µL
Platelet count 134×103/µL
Random blood sugar 128 mg%
Blood urea nitrogen 12 mg%
Serum creatinine 0.92 mg%
Erythrocyte sedimentation rate 28 mm in the first hour
Figure 3 (A) B-­scan ultrasound showing exudative retinal detachment
C reactive protein 21 mg/dL
of the right eye (indicated by the red arrow) and (B) choroidal mass
L, lymphocytes; M, monocytes; MCV, mean corpuscular volume; P, polymorphonuclear exhibiting high internal reflectivity (indicated by the red arrow) and mild
cells.
vitreous hemorrhage (indicated by the red asterisk).
2 Haque OI, et al. BMJ Case Rep 2023;16:e254392. doi:10.1136/bcr-2022-254392
 Case report

BMJ Case Rep: first published as 10.1136/bcr-2022-254392 on 15 May 2023. Downloaded from http://casereports.bmj.com/ on November 5, 2024 at Franklin Square Hospital Health
Figure 6 (A) Microscopic view (40× magnification) of the H&E
stained fine needle aspirate from the axillary lymph node showing
epithelioid granuloma (black arrow), lymphocytes and multinucleated
giant cells of Langhans; the smear was negative for acid-­fast Bacillus.
Inset: magnified view of the granuloma. (B) Microscopic view of the
skin biopsy stained with H&E at 100× magnification showing an area of
caseous necrosis in the centre surrounded by multinucleated giant cells,
epithelioid cells, foamy cells, and a rim of lymphocytes. Inset: magnified
Figure 4 Posteroanterior view of the chest radiograph showing view of two granulomas.
cavitary lesion in the left upper lobe (arrows).
multinucleated giant cells. Extrapulmonary TB (EPTB) commonly
it remains a major public health problem estimated to infect affects lymph nodes, accounting for 35%–40% of cases.5 The

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roughly 23% of the world’s population.1 However, only 10% of typical presentation is painless swelling of a single group of
the infected population develop active TB, while the other 90% lymph nodes that progresses slowly, with a median size of 3 cm
have latent TB that may activate at any time during their life.1 2 and occasionally reaching up to 8–10 cm in diameter.6
In this report, we describe a case of TB infection involving the The morphology of skin lesions along with the histopatho-
eye, skin, axillary lymph nodes and lungs, leading to extensive logic findings was consistent with lupus vulgaris. Cutaneous
multisystem disseminated disease. TB is a relatively uncommon presentation of EPTB, accounting
The intraocular inflammation, iris neovascularisation for approximately 1.5% of all EPTB manifestations.7 In adults,
(figure 2A–C), choroidal tubercle along with vitreous haemor- lupus vulgaris is the most prevalent form of cutaneous TB. The
rhage, and exudative retinal detachment observed on the b-­scan lesion typically starts as a small reddish-­brown nodule that grad-
aligned with the intraocular TB diagnosis. Choroidal tubercles ually spreads centrifugally and becomes raised and infiltrated.
are the most commonly observed finding in patients with intra- Lupus vulgaris is a paucibacillary form of cutaneous TB that
ocular TB.2 3 Intraocular TB predominantly affects immunocom- generally occurs in individuals with moderate or high degrees
petent individuals, the majority whom have poor visual acuity of immunity, as evidenced in our case by a strongly positive
(20/200 or worse) at presentation and tend to have unfavourable tuberculin skin test. Bacterial culture is generally negative. Most
outcomes, often necessitating enucleation/evisceration or exen- forms of cutaneous TB respond well to chemotherapy and have
teration of the affected eye.4 a favourable prognosis, although complications such as scar-
The patient was also found to have bilateral axillary lymph- ring, contractures, ulceration and tissue destruction can occur.8
adenopathy, with the largest lymph node measuring 3×1.3 cm In approximately 4% of patients, lupus vulgaris can progress to
on ultrasonography. The FNA of the lymph node revealed char- squamous cell carcinoma.9
acteristic epithelioid non-­caseating granulomas and occasional In the present case, the M. tuberculosis infection involved
the eye, skin, axillary lymph nodes and lungs, leading to exten-
sive multisystem disseminated disease. The apparent cause of
dissemination could not be elucidated in this immunocompe-
tent patient. Disseminated TB infections are commonly seen
with some form of immunosuppression. About 15%–20% of
all cases of TB in immunocompetent patients present as EPTB,
but it accounts for more than 50% of the cases in HIV-­positive
individuals.5 10 Extrapulmonary involvement may occur either
in association with clinically apparent pulmonary TB or in isola-
tion, without any clinical or laboratory evidence of pulmonary
infection.2 Although the immune system plays a crucial role in
containing the spread of the infection, the Mycobacterium tuber-
culosis bacilli have evolved several mechanisms to escape the
immune system, which greatly enhance its survival in the host.
These mechanisms include—inhibition of macrophage phago-
Figure 5 Ultrasonography of the axillary region showing cytosis, inhibition of the fusion of phagosomes with lysosomes,
conglomerates of enlarged hypoechoic lymph nodes in the right (A) and inhibition of the maturation and acidification of phagolysosomes
left (B) axillary region. The largest lymph nodes have been marked with and the inhibition of oxidative stress.11–13 Some strains of M.
red asterisks (*) for reference. tuberculosis inhibit apoptosis and autophagy.14
Haque OI, et al. BMJ Case Rep 2023;16:e254392. doi:10.1136/bcr-2022-254392 3
Case report

BMJ Case Rep: first published as 10.1136/bcr-2022-254392 on 15 May 2023. Downloaded from http://casereports.bmj.com/ on November 5, 2024 at Franklin Square Hospital Health
The mainstay of management of disseminated TB involves a Twitter Obaid Imtiyazul Haque @obaidimtiyaz
combination of multiple antibiotics for a minimum of 6 months. Contributors OIH, SAR and ZS were responsible for drafting of the text, sourcing
The patient was treated as per the Indian EPTB guidelines.15 and editing of clinical images, investigation results, drawing original diagrams and
The drug sensitivity test, using CB-­NAAT, indicated sensitivity algorithms, and critical revision for important intellectual content. OIH, SAR and
ZS gave final approval of the manuscript. Is the patient one of the authors of this
to rifampin. The initial phase of treatment involved four drugs manuscript? No.
(isoniazid, rifampin, pyrazinamide and ethambutol), for 2 months
Funding The authors have not declared a specific grant for this research from any
followed by three drugs (rifampin, isoniazid and ethambutol) for funding agency in the public, commercial or not-­for-­profit sectors.
another 4 months after an assessment of patient’s response to
Competing interests None declared.
treatment. Throughout the treatment period, the patient was
closely monitored to assess the patient’s response and for any Patient consent for publication Consent obtained directly from patient(s).
adverse effects of the drugs. While disseminated TB typically has Provenance and peer review Not commissioned; externally peer reviewed.
a poor visual outcome, the patient showed encouraging signs Case reports provide a valuable learning resource for the scientific community and
of progress as their lymphadenopathy and skin lesions resolved can indicate areas of interest for future research. They should not be used in isolation
after receiving treatment.4 to guide treatment choices or public health policy.

ORCID iD
Obaid Imtiyazul Haque http://orcid.org/0000-0002-8396-7019

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4 Haque OI, et al. BMJ Case Rep 2023;16:e254392. doi:10.1136/bcr-2022-254392