clinical manifestation of mott

Asysyukriati R. Prawiro

Literature Review III

Sunday, April 23th 2012

PULMONOLOGY RESIDENT

FACULTY MEDICINE UNIVERSITY OF INDONESIA

Mycobacterium other than tuberculosis (MOTT)

Non tuberculous mycobacterium (NTM)

Atypical mycobacterium (AM)

Opportunistic mycobacterium

Unclassified mycobacterium

Annonymous mycobacterium

Environmental mycobacterium

All mycobacterial species other than Mycobacterium

tuberculosis complex and M. leprae

Jurnal Tuberkulosis Indonesia. 2004;1:1-52.

Am J Respir Crit Care Med. 2007;175:367-416.

Arch Pathol Lab Med. 2008;132:1333-40.

MOTT have been known since the time of

Robert Koch but historically

overshadowed by tuberculosis and dismissed

as contaminant

With advances in molecular microbiology and

knowledge

as true pathogens and important causes of

human infection

Difficult to diagnose and to treat

Am J Respir Crit Care Med. 2007;175:367-416.

Arch Pathol Lab Med. 2008;132:1333-40

Family: Mycobateriaceae

Ordo : Actynomycetales

Ubiquitous in the

environment

Can cause both

asymptomatic infection

and symptomatic disease

in humans

4 clinical syndromes

Lung disease

Lymphadenitis

Skin/soft

tissue/skeletal disease

Disseminated disease

Jurnal Tuberkulosis Indonesia. 2004;1:1-52

Am J Respir Crit Care Med. 2007;175:367-416.

Indian J Med Res. 2004;120:290-304.

Widely distributed in the environment with

high isolation rates worldwide

soil, natural water, tap water, water used in

showers, surgical solutions, food, birds

Human disease is suspected to be acquired

from environmental exposures

No evidence of animal-to-human or human-to-

human transmissions

Am J Respir Crit Care Med. 2007;175:367-416

Proc Am Thorac Soc. 2006;3:285-92

Am J Respir Crit Care Med. 2011;183:788-824.

Incidence

• Incidence rates vary from 1.0 to 1.8 cases per 100,000 persons

• Have been seen in most industrialized countries

• ↑ Cases ~ HIV

Prevalence

• There is not substantially more or better information about MOTT disease prevalence than that published in the 1997 ATS statement on MOTT

Am J Respir Crit Care Med. 2007;175:367-416

Proc Am Thorac Soc. 2006;3:285-92

Am J Respir Crit Care Med. 2011;183:788-824.

Predisposing factors Immunocompromized

Underlying pulmonary pathology

COPD

History of Tb

ILD / IPF

Silicosis

Asbestosis

Bronchiectasis

Cystic fibrosis

Cancer

The most common inf.

(pulmonary)

MAC/MAI

M. kansasii

M. abscessus

M. xenopi

M. malmoense

Jurnal Tuberkulosis Indonesia. 2004;1:1-52

Am J Respir Crit Care Med. 2007;175:367-416

Respirology. 2009;14:12-26

Another factors

Smoking (>30 pack/year)

Alcohol

Cardiovascular disease

Chronic liver disease

Pasca gastrectomi

•Medicinus. 2008;60-2.

Medicinus. 2008;60-2

ATSIdentified more than 125 MOTT species

Daley CL and Griffith DE identified more

than 140 MOTT species, at least 40 of which

are associated with lung infection

slowly growing mycobacteria (SGM) and

rapidly growing mycobacteria (RGM)

Runyon system 4 categories (description,

growth and pigment production)

Int J Tuberc Lung Dis. 2010;14:665–71.

Int J Tuberc Lung Dis. 2010;14:665–71.

Am J Respir Crit Care Med. 1997;156:1-25

Am J Respir Crit Care Med. 1997;156:1-25

Am J Respir Crit Care Med. 1997;156:1-25

Arch Pathol Lab Med. 2008;132:1333-40

A

B

C

D

•Nontuberculous mycobacteria. [cited 2010 June 24th]. Available from:URL:http://knoll.google.com/k/nontuberculous-mycobacteria#. •Nontuberculous mycobacteria. [cited 2010 June 24th]. Available from:URL:http://knoll.google.com/k/nontuberculous-mycobacteria#.

http://knoll.google.com/k/nontuberculous-mycobacteria#.

Port de entry

Abrasions in the skin (esp. M.

marinum)

Surgical incisions (esp. central

catheters)

Oropharyngeal mucosa (cervical )

Gastrointestinal

Respiratory tract

• Port de entry lymph reg

• Lung infect. ~ MTb

Host defense, mucociliary

clearence and

tracheobronchial secretion

Predisposing factors

• Granulomatous lession =

MTb

Jurnal Tuberkulosis Indonesia. 2004;1:1-52

Am J Respir Crit Care Med. 2007;175:367-416.m AAP Grand Rounds .2003;51:1-6

Still not completely understood

Pathogenesis 3 important observations (over

the past two decades)

1. HIV patientsdisseminated NTM infections typically

occurred only after the CD4 T-lymphocyte number <

50/ul

2. HIV-uninfected patient genetic syndromes of

disseminated NTM infection associated with specific

mutations in IFN γ & IL-12 synthesis and response

pathways

Am J Respir Crit Care Med. 2007;175:367-416.

(IFN-γ receptor 1 [IFNR1], IFNR2, IL-12

receptor 1 subunit [IL12R1], IL12p40, the signal

transducer and activator of transcription1

[STAT1], and the nuclear factor- essential

modulator [NEMO])

3. Association bronchiectasis, body habitus,

predominantly in postmenopausal women (e.g.,

pectus excavatum, scoliosis, mitral valve

prolapse)

Am J Respir Crit Care Med. 2007;175:367-416.

1. Pulmonary disease

2. Lymphadenitis

3. Skin/soft tissue/skeletal

4.Disseminated

4 clinical syndromes

Jurnal Tuberkulosis Indonesia. 2004;1:1-52

Am J Respir Crit Care Med. 2007;175:367-416

Respirology. 2009;14:12-26

Not specific Alike tuberculosis or underlying pulmonary

pathology

Cough sputum

Lose appétit

↓ body weight

Could be with lymphadenophati/hepatosplenomegali

Have predisposing factors

Am J Respir Crit Care Med. 2007;175:367-416.

Missouri Department of Health and Senior Services- Communicable Disease Investigation Reference Manual

Night sweat

Fatigue

Hemoptysis

1 (a) Axial and (b) coronal HRCT images

taken at presentation show a nodular and

tree-in-bud appearance peripherally in both

lungs, more marked on the right side with

underlying ground glass opacities

Axial HRCT image shows

a marked improvement

after nine weeks of

treatment

Singapore Med J 2008; 49: e47-9

Am J Clin Pathol 2001;115:755-762

The most common 1-5 years old and cervical

lymphadenitis ( head and neck)

Typically firm, non-tender, and painless, with non-

erythematous overlying skin

Non-fluctuant: lymph node suppuration and

spontaneous drainage may occur after caseation

and necrosis development

Arch Pathol Lab Med. 2008;132:1333-40

Journal of Microbiological Methods. 2008;75:1–11

Fever, weight loss, fatigue, and malaise are

usually absent or minimal.

Lymph node involvement typically occurs

between six to nine months following the initial

infection

HIV patient subclinical infection after

treatment with antiretroviral

Arch Pathol Lab Med. 2008;132:1333-40

Journal of Microbiological Methods. 2008;75:1–11

Common etiology :

MAC another cased by RGM, M. malmoense,

M. kansasii M.haemophilum, M. interjectum, M.

palustre, M. tusciae, M. heidelbergense, M.

elephantis, M. lentiflavum dan M. bohemicum

Arch Pathol Lab Med. 2008;132:1333-40

AAP Grand Rounds. 2003;51:1-6

The spectrum of STSIs is broad and ranges from

chronically draining, localized abscesses/nodules

to tenosynovitis to frank osteomyelitis.)

Typically indolent, and the clinical course variable

Predilection

direct inoculation such as penetrating trauma

or soilage of open wounds and fractures

Arch Pathol Lab Med. 2008;132:1333-40

Am J Respir Crit Care Med. 2007;175:367-416

Iatrogenically cause infections following

intravenous and peritoneal catheters, shunts,

intramuscular injections, cosmetic surgery

procedures, laser in situ keratomileusis

procedures, and postsurgical wounds

Minor cutaneous infections may resolve

spontaneously during the course of 8 to 12 mo.

More serious disease, such as osteomyelitis,

will likely progress over time

Arch Pathol Lab Med. 2008;132:1333-40

Am J Respir Crit Care Med. 2007;175:367-416

STSIs..

The most common etiology

M. fortuitum, M. abscessus or M. chelonae

Other species are associated with certain

clinical syndromes

Swimming pool granuloma/ fish tank granuloma

Mycobacterium marinum

Exposure to some type of marine environment

(eg, fish, crustaceans, fish tanks)

Presents as granulomatous lesions Arch Pathol Lab Med. 2008;132:1333-40

usually on portions of the extremities

prone to abrasions

begin as papules that then ulcerate and

scar

often localized, but some patients can

develop a nodular lymphangiitis similar to

sporotrichosis

Arch Pathol Lab Med. 2008;132:1333-40

Zahid M. Qureshi MD, Pediatric Tuberculosis Myths & Truths

Burulli ulcer

Mycobacterium ulcerans

Starts as a pruritic nodule that eventually

degenerates into a large

Irregular

Undermined ulcer

Chronic

Necrotic skin lesions of the extremities

In the tropics and Australia

Arch Pathol Lab Med. 2008;132:1333-40

Zahid M. Qureshi MD, Pediatric Tuberculosis Myths & Truths

•CD4 < 50 sel/μL

•Etiology : 95 % MAC

The most common

symptoms fevers,

night sweats, and weight

loss-- Diarrhea and

abdominal pain,

hepatoslenomegali ,

Mycobacterial spindle cell

pseudotumors syndrome

Immunosupresion

(transpl, cancer, steroid)

Infliximab & etanercept

Etiology: MAC,

M. kansasii, M. chelonae,

M. abscessus &

M. haemophilum.

Symptoms: fevers

Some spesies

subcutaneous nodul or

abses

Arch Pathol Lab Med. 2008;132:1333-40

Am J Respir Crit Care Med. 2007;175:367-416.m

H

I

V

N

o

n

H

I

V

Disseminated atypical mycobacterial tuberculosis with

generalized cutaneous lesions in a boy with acute

lymphoblastic leukemia in remission AAP Grand Rounds. 2003;51:1-6

Zahid M. Qureshi MD, Pediatric Tuberculosis Myths & Truths

Journal of Infection. 2007;55:484-7

1. MOTToportunistic in the environment

2. MOTT : All mycobacterial species other than

M. tuberculosis complex and M. leprae

3. MOTTdiseasepredisposing factors

4. Port de entry infection Abrasions in the skin,

surgical incisions, oropharyngeal mucosa,

gastrointestinal, respiratory tract and no

evidence of animal-to-human or human-to-

human transmissions.

5. Clinical manifestation 4 clinical

syndromes (pulmonary disease,

lymphadenitis, skin/soft tissue/skeletal

disease, disseminated disease)

6. The most commont manifestation is

pulmonary disease