nemoci-sympt/PLICNI/sarkoidoza/zhorsujici-faktory

ACCESS trial

• Collected data on 704 patients with newly diagnosed
• Biopsy specimen–proven sarcoidosis
• Numerous environmental exposures that were moderately linked to sarcoidosis risks
• Agricultural employment,
• Mold or mildew,
• Musty odors at work
• Pesticide-using industries
• Risk of developing sarcoidosis increased with the extent of tobacco use
• Validated results of previous studies [8]

• Possible triggers include
• Propionibacterium acnes
• Mycobacteria
• Mold or mildew [8]

Agent Orange exposure

• The Veteran claims that the February 2008 rating decision denying service connection for sarcoidosis was clearly and unmistakably erroneous because the RO erred by failing to apply the statutory and regulatory provisions concerning service connection for chronic diseases, or diseases presumed to be service connected as a result of Agent Orange exposure. [5]
• Sarcoidosis first manifested in service or manifested to a compensable degree within a year of service
• 2008 rating decision denying service connection for sarcoidosis [5]

BTNL2 gene single nucleotide polymorphism (rs2076530 G›A)

• Increased association between sarcoidosis susceptibility independent of HLA class II alleles
• Affects T-lymphocyte activation and regulation
• BTNL2 gene resides in the major histocompatibility complex class II region of chromosome 6p,
• B7 family T-cell-negative costimulatory molecule related to the CD80 and CD86 costimulatory receptors
• Nonfunctional BTNL2 molecule
• May lead to exaggerated lymphocyte activation
• Factor in the pathogenesis of sarcoidosis [3]

Butyrophilin-like 2 receptor gene polymorfismy

Emissions from wood-burning stoves

• [8]

Genetika

• Class I human leukocyte antigen (HLA) susceptibility alleles
• Consistently associated with sarcoidosis risk include
• HLA-A*1,
• HLA-B*7,
• HLA-B*8
• Which exist in most populations with acute sarcoidosis [3]

HLA-DRB1*0301-positive

• T-cells from sites of sarcoid disease activity
• Including Kveim–Siltzbach skin reactions show
• A restricted variable-alpha region (Valpha) and variable-beta region of the T-cell receptor (TCR)
• Indicating TCR oligoclonal expansion in response to a limited group of antigens

• BAL T-cells from HLA-DRB1*0301-positive patients with sarcoidosis
• Predominantly express Valpha2.3 (AV2S3+)
• These T-cells are reacting to the unknown sarcoid antigen(s) when presented by the HLA-DRB1*0301 molecule [3]

HLA-DRB1*0301 genotype

• Largely express the TCR Valpha2.3 (AV2S3+).
• Increased numbers of AV2S3+ CD4+ BAL T-cells
• May represent an acute phase of sarcoidosis
• Indicating clonal proliferation in response to inciting antigen(s) [3]

• Upon stimulation by nonspecific mitogens
• Dominant TH1 cytokine profile in BAL T-cells from patients with pulmonary sarcoidosis [3]

HLA-DRB1*1501/HLA-DQB1*0602 haplotype

• Chronic and severe pulmonary sarcoidosis consistently associated [3]

Inorganic particles

• [8]

Insecticides

• [8]

Moldy environments

• Have been reported [8]

Mutations which can lead to sarcoidosis

“Early onset sarcoidosis (EOS)”

“Blau syndrome”

• Found in children younger than four years
• Rare autosomal dominant disorders with
• Arthritis
• Granulomatous inflammation of the eyes and skin [6]
• Mutations in the nucleotide binding oligomerisationdomain (NOD)-2 gene
• This leads to a hyperreactive defense mechanism with granuloma production
• TNF-alpha and IFN-gamma seem to play a major role [6]

Mycobacteria and propionibacteria

• Microbial nucleic acid analyses suggest that mycobacteria and perhaps propionibacteria play a role in the pathogenesis of arcoidosis
• 9- to 19-fold higher incidence in histopathological samples compared with controls
• Including immune responses against some microbe-derived antigens
• Intracellular persistence of such bacterial antigens
• Failure to clear nondegradable antigeneprotein complexes in patients with certain genotypes may explain chronic sarcoidosis [4]

Mno, pak bych se terapie kortikoidy tedy dost bála, protože to pak budou mít případné bakterie ještě o to víc navrch. Spíše bych přemýšlela, jak podpořit pacienta v tom, aby jeho buňky dokázaly degradovat a odklidit to, co jim nejde. Jak podpořit fagocytozu, autofagocytozu a oxidační vzplanutí ap. Na Druhou stranu, pokud by příčinou byly anorganické zbytky třeba berrilium aj., pak by naopak kortikoidy dávaly smysl. Velmi by mi tedy jako pacientovi záleželo, aby se i po stanovení diagnózy sarkoidózy dál pátralo po tom, co to vyvolalo. Takže ano, musela bych podstoupit biopsii nějaké léze a záleželo by, zda je dostupná a jestli se z toho podaří analýzou PCR nebo imunoanalýzou zjistit, zda to v sobě něco má... mno a samozřejmě by záleželo, zda jsou tyto náročné metody v dané nemocnici vůbec dostupné.

TNF polymorphisms

• May also play a role in
• Sarcoid disease severity
• In patients with erythema nodosum [3]

Tree pollen

• [8]

Monozygotic twins

• Increased concordance in monozygotic twins [3]

Rasa

African-Americans with sarcoidosis

• More likely to suffer from more chronic and fatal disease types, as well as erythema nodosum and eye, liver, and bone marrow involvement, compared with Caucasians [3]