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Live bacteria have been found, with significant frequency of occurrence, in sarcoid tissue. They’re of a variety called Cell Wall Deficient (CWD), or L-Forms, or coccoid forms. They’ve adapted due to a resistance to the penicillin antibiotics, which attack bacterial cell walls. See History of Research into Cell Wall Deficient Bacteria (L-Forms).

These bacteria are very small, and difficult to see in pathology unless special stains are used. They are difficult to culture, which can explain why they are not identified during conventional lab testing. It may be that several types of bacteria work together to cause sarcoidosis and not all of them are necessarily present in any one patient. See Intracellular Bacteria

Many studies have suggested a bacterial cause for sarcoidosis.

This review discusses the biology and behavior of Propionibacterium acnes (P.acnes), a dominant bacterium species of the skin biogeography thought to be associated with transmission, recurrence and severity of disease. More specifically, we discuss the ability of P. acnes to invade and persist in epithelial cells and circulating macrophages to subsequently induce bouts of sarcoidosis, low-grade inflammation and metastatic cell growth in the prostate gland.
P. acnes-Driven Disease Pathology: Current Knowledge and Future Directions

Sarcoidosis is a non-caseating granulomatous disease for which a role for infectious antigens continues to strengthen.
Bacterial Signals in Sarcoidosis.
Dual analysis for mycobacteria and propionibacteria in sarcoidosis BAL. 

This indigenous low-virulence bacterium can cause latent infection in the lungs and lymph nodes and persist in a cell-wall-deficient form. This dormant form of P. acnes can be activated endogenously under certain environmental conditions and then proliferate in cells at the site of latent infection. In patients who are hypersensitive to this endogenous bacterium, granulomatous inflammation is triggered by intracellular proliferation of the bacterium. Some of the proliferating bacteria may escape from isolation by the granuloma and spread to other organs via the lymphatic and blood streams. The spread of infective P. acnes might cause a new latent infection in systemic organs such as the eyes, skin, and heart. Latent infection established in certain systemic organs will be reactivated simultaneously by the next triggering event, resulting in the onset of systemic sarcoidosis.
Etiologic Aspect of Sarcoidosis as an Allergic Endogenous Infection Caused by Propionibacterium acnes

In this study, Localization of Propionibacterium acnes in granulomas supports a possible etiologic link between sarcoidosis and the bacterium, published in Modern Pathology (May 2012), Japanese scientists tested the hypothesis that P. acnes is an etiologic agent of sarcoidosis. This is a bacteria normally found on human skin, the same bacteria that causes acne. Surprisingly, this bacteria has been found inside sarcoid granulomas and in the fluid washed from the surface of the lungs (BAL) during diagnostic procedures.

Researchers identified a P. acnes trigger-factor protein that induced pulmonary granulomas only in mice with latent P. acnesinfection in their lungs. Eradication of P. acnes by antibiotics in these mice prevented granulomas, which might explain the recently reported effectiveness of tetracyclines for treating sarcoidosis.  They found greater than 50% reactivity: 57% in lung tissue and 88% in lymph node. They also found bodies that might be intact forms of intracellular bacteria, because they lacked a cell wall structure. This study concluded that sarcoidosis may arise from an imbalance of Th1/Th17 immune responses against viable P. acnes, but not M. tuberculosis complex.

Th1 and Th17 immune responses to viable Propionibacterium acnes in patients with sarcoidosis.

The Center for Disease Control published, in Emerging Infectious Diseases, a 2002 report from Vanderbilt University School of Medicine and Veterans Affairs Medical Center, titled Molecular Analysis of Sarcoidosis Tissues for Mycobacterium Species DNA. This study "provide(s) evidence that one of a variety of Mycobacterium species, especially organisms M. tuberculosis, is found in most patients with sarcoidosis".

R.M Du Bois, et al, of the Royal Brompton Hospital and Imperial College in London wrote a Review titled, “Is There a Role for Microorganisms in the Pathogenesis of Sarcoidosis?” which was published in 2003 in the Journal of Internal Medicine. They concluded "that microbes are a likely trigger (but not as an infection) in a genetically predisposed individual and that this initial event culminates in the sarcoidosis granulomatous response.

In 2001, Dubois,et al, published an article, Sarcoidosis: genes and microbes - soil or seed?, in the WASOG journal Sarcoidosis, that concludes "that one or more microbes behaving in a non-infectious fashion in a genetically predisposed individual trigger the sarcoidosis granulomatous response".

A landmark Swedish study from 2002, Presence of Rickettsia Helvetica in Granulomatous Tissue of Patients with Sarcoidosis, reports finding Rickettsia and various bacteria in 86% of tissue samples. They conclude "these results support the hypothesis that rickettsiae may contribute to a granulomatous process, as is seen in sarcoidosis."

Lida Mattman's study, Growth of Acid Fast L Forms From the Blood of Patients With Sarcoidosis, was published in Thorax and reports that various Cell Wall Deficient bacteria were found in 95% of sarcoid biopsy samples.

The 1999 German study by Grosser M, Luther T, Muller J, Schuppler M, Bickhardt J, Matthiessen W, Muller M., Detection of M. Tuberculosis DNA in Sarcoidosis: Correlation With T-cell Response, found Mycobacteria in 64% of tissue samples.

D.R. Moller from Johns Hopkins University School of Medicine, concludes in his paper titled Treatment of Sarcoidosis- from a basic science point of view published in the Journal of Internal Medicine in 2003, "Given evidence for a genetic predisposition to sarcoidosis, these findings suggest that the etiology of systemic sarcoidosis is linked to genetically determined enhanced Th1 immune responses to a limited number of microbial pathogens."

Please see this presentation on the "Infectious Etilology of Sarcoidosis"by Stephan Tilley M.D., Department of Medicine, Pulmonary Division, UNC.

Dysfunctional Immune System in Sarcoidosis

This paper, http://www.ncbi.nlm.nih.gov/pubmed/22759465, explains researchers' evaluation of cells washed from the lining of the lungs of sarcoidosis patients and healthy controls. They found that sarcoidosis patients' cells had a less than normal ability to express an antimicrobial peptide called cathelicidin, which is stimulated by the active form of vitamin D (produced in abundance in those with sarcoidosis). Cathelicidin production is also inhibited by tumor necrosis factor-α (TNFα), a vitD3 antagonist that is elevated in active sarcoidosis.

There is much to be studied to determine how and why sarcoidosis patients have an altered immune system response to bacteria.

Additional studies citing a bacterial cause for sarcoidosis (click here)

Molecular identification of bacterial DNA in the chorioretinal scars of chronic granulomatous disease.

The Use of Tetracyclines for the Treatment of Sarcoidosis

Molecular evidence for the role of mycobacteria in sarcoidosis: a meta-analysis

Chlamydophila bacteria prevalent in Sarcoidosis patients

Detection of antibodies against Borrelia burgdorferi in patients with uveitis.

[Borrelia burgdorferi may be the causal agent of sarcoidosis]

“Determination of antibody of Borrelia burgdorferi in the serum of patients with sarcoidosis and its significance”

“The diagnostic value of anti-BB-antibody estimation in acidosis”

“Detection of Borrelia burgdorferi DNA in granulomatous tissues from patients with sarcoidosis using polymerase chain reaction in situ technique”

Positive Lyme titers in a patient with active sarcoidosis.

"Seroprevalence of anti-Borrelia antibodies amoung patients with confirmed sarcoidosis in a region of Japan where Lyme borreliosis is endemic"

Molecular Analysis of Sarcoidosis Tissues for Mycobacterium Species DNA

Presence of Rickettsia helvetica in granulomatous tissue from patients with sarcoidosis.

Pulmonary sarcoidosis: could mycoplasma-like organisms be a cause?

Growth of acid fast L forms from the blood of patients with sarcoidosis.

Histologic observations of variably acid-fast pleomorphic bacteria in systemic sarcoidosis: a report of 3 cases.

The nature and physical characteristics of a transmissible agent from human sarcoid tissue.

Quantitative analysis of mycobacterial and propionibacterial DNA in lymph nodes of Japanese and European patients with sarcoidosis.

The presence of Propionibacterium spp. in the vitreous fluid of uveitis patients with sarcoidosis.

Vitamin D, innate immunity, and sarcoidosis granulomatous inflammation: insights from mycobacterial research.

Considering an infectious etiology of sarcoidosis.

Mycobacteria have been isolated from a majority of sarcoidosis patients

"Mycobacterium" is a species of bacteria which are very similar in many ways. Mycobacterium tuberculosis causes TB and mycobacterium leprae causes leprosy. This bacteria has been isolated from a majority of sarcoidosis patients.

Mycobacterial DNA in recurrent sarcoidosis in the transplanted lung - a PCR-based study on four cases

Identification of mycobacterial DNA in cutaneous lesions of sarcoidosis.

Identification of Mycobacterium avium complex in sarcoidosis.

Quantitative analysis of mycobacterial and propionibacterial DNA in lymph nodes of Japanese and European patients with sarcoidosis.

Opportunistic infections and sarcoidosis [Article in French]

Sensitive differential detection of genetically related mycobacterial pathogens in archival material.

Detection of Mycobacterium avium complex in cerebrospinal fluid of a sarcoid patient by specific polymerase chain reaction assays.

Disseminated cutaneous Mycobacterium avium-intracellulare resembling sarcoidosis.

Donor-acquired sarcoidosis

Sarcoidosis has developed in non-sarcoidosis transplant recipients who have received tissues or organs from donors who were not suspected or known to have active sarcoidosis. Donor-acquired sarcoidosis strengthens the view that sarcoidosis is caused by bacteria.

Reported cases of donor-acquired sarcoidosis:

Cardiac sarcoidosis and heart transplantation: a report of four consecutive patients

Transmission of sarcoidosis via cardiac transplantation.

Transmission of sarcoidosis via cardiac tranplant

Possible transmission of sarcoidosis via allogeneic bone marrow transplantation.

Donor-acquired sarcoidosis.

Granulomatous pneumonitis following bone marrow transplantation.

Pulmonary sarcoidosis following stem cell transplantation: is it more than a chance occurrence?

This experiment suggests an infectious cause of sarcoidosis.

Experimental Skin Sarcoidosis In A Doctor Volunteer

Reported cases of sarcoidosis lesions at venipuncture sites also suggest an infectious etiology for sarcoidosis.

Cutaneous sarcoidosis in venepuncture sites.

Cutaneous sarcoidosis in blood donation venepuncture sites.

Familial Aggregation

The ACCESS study, the largest study of sarcoidosis in the US sponsored by the National Institutes of Health, found that the risk for sarcoidosis among parents and siblings of sarcoidosis patients increased five-fold.

No genetic factor has ever been identified to explain familial occurrences of sarcoidosis, although this has been studied - as noted below. The alternative explanation is that family members share environmental bacterial exposure.

Familial Aggregation in Sarcoidosis

[Familial sarcoidosis. Apropos of 22 families]

A sarcoidosis genetic linkage consortium: the sarcoidosis genetic analysis (SAGA) study.

Risk of Sarcoidosis for First- and Second-Degree Relatives

Familial aggregation of sarcoidosis. A case-control etiologic study of sarcoidosis (ACCESS).

Disease Clusters

Clusters of the disease have been reported, leading to speculation about person-to-person transmission.

NEW DATA ALTER VIEW OF SARCOIDOSIS

Bacteria in Sarcoidosis and a Rationale for Antibiotic Therapy in this Disease
By Alan R Cantwell, Jr., M.D.

”There is evidence dating back to the 1930s and 1940s by various investigators (e.g., Gullberg, Hollstrom, Schaumann) showing that bacteria, related to tuberculosis bacteria, are associated with sarcoidosis. This research has been largely ignored, prompting Moscovic to declare in 1982: "Had all the work and effort spent on proving a non-mycobacterial nature of the disease been channeled into pursuing these clues, the etiology of sarcoidosis may have long been clearly established and a more rational approach to diagnosis and treatment could by now have been developed.

Scientists could spend another 100 years trying to identify each of the cell wall deficient bacteria that trigger the abnormal sarcoidosis immune system reaction in predisposed individuals but isn't necessary to know the identity of these offending organisms in order to eliminate them. Sarcoidosis provides a unique clue to the presence of mycoplasma in the cells of the immune system when a Jarisch-Herxheimer reaction is elicited with antibiotics.

Initiating treatment with antibiotics to provide a therapeutic probe (a time-honored medical technique) can verify the presence of these bacteria without expensive testing and validate the necessity of antibiotic treatment.”

See Immune System.  

Updated July 13, 2017