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 Bacteria in Sarcoidosis, and a Rationale for Antibiotic Therapy in this Disease
Author: Alan R Cantwell, Jr (---.dsl.dock.net)
Date:   10-05-03 21:07

Bacteria in Sarcoidosis and a Rationale for Antibiotic Therapy in this Disease


Author: Alan R Cantwell, Jr., M.D.
Los Angeles, California,
email: AlanRCan @aol.com

Paper Type: Review
Paper Type: Comment upon "Marshall TG, Marshall FE: Antibiotics in Sarcoidosis - Reflections on the First Year. JOIMR 2003;1(3):2"
Published:30 Sept 2003

Please cite as: Cantwell AR Jr. Bacteria in Sarcoidosis and a Rationale for Antibiotic Therapy in this Disease. JOIMR 2003;1(5):1

Introduction

Sarcoidosis is generally considered a disease of unknown etiology. However, there is an impressive body of literature suggesting that sarcoidosis is a microbial infection associated with cell wall-deficient (L-forms) forms of bacteria. Among the most important are the findings of cell wall-deficient (CWD) mycobacteria in sarcoidosis by Judge and Mattman [1]; and Moscovic's histologic studies demonstrating mycobacterial L-forms in vivo (i.e. within the body) in diseased lymph nodes (glands) from sarcoidosis patients [2].

Sarcoidosis is a systemic disease characterized by the formation of granulomas and frequent involvement of the lungs and lymph nodes. In this respect, the disease has some similarity to tuberculosis (TB) and also to leprosy (Hansen's disease). Both TB and leprosy are caused by acid-fast mycobacteria; TB is caused by Mycobacterium tuberculosis; leprosy by M. leprae.

According to Moscovic, "One of the oldest clinical observations concerning sarcoidosis and TB is that either disease may turn into the other, and occasionally the two diseases may coexist within the same individual. Isolated cases of sarcoidosis changing into tuberculosis, which again reverted to sarcoidosis, have also been reported [3]." In addition, sarcoidosis has a peculiar relationship to cancer, particularly lymphoma [4]. Most significantly, pathologists occasionally encounter sarcoidal granulomas in lymph nodes that drain cancer tissue. A PubMed computer search of "cancer + sarcoidosis" currently yields over 2300 references to the scientific literature (http://www.ncbi.nlm.nih.gov/PubMed/).

Histologic Findings of CWD bacteria in Sarcoidosis

Since the 1970s Moscovic and his associates have presented histologic and immunologic evidence in sarcoidal lymph nodes showing "pleomorphic chromogens", tiny "round bodies", larger "yeast-like bodies" and "vacuolated forms", all suggestive of mycobacteria-like CWD microbes [2,3]. The close association of sarcoidosis with cancer is further evident in a 1996 study by Alavi and Moscovic identifying CWD forms of M. tuberculosis "complex" in sarcoid lymph nodes, and also in lymph nodes draining carcinoma [5].

My research into the role of CWD bacteria in sarcoid evolved out of similar research into the role of CWD bacteria in dermatologic diseases of unknown etiology [6], and also from my keen interest in the controversial microbiology of cancer. In 1981-1982, Cantwell reported in three separate publications the identification of pleomorphic [more than one type of form] CWD variably acid-fast bacteria, primarily in the coccoid form, in the histopathologic tissue specimens from sarcoidosis of the skin, lymph nodes, and lungs (7-9). Larger forms of the sarcoid microbe were also observed in vivo and were morphologically similar to "large body" and "giant L-forms" previously described in vitro (outside the body) in laboratory cultures as valid CWD forms (10). The microbes I observed in sarcoid were similar in appearance to bacteria associated with certain forms of cancer and with certain immunologic diseases of unknown etiology, as previously reported by various cancer investigators over the past century. This research has been reviewed in my book, The Cancer Microbe [11]. The possible role of pleomorphic CWD bacteria in cancer has also been reviewed by pathologist P Macomber [12].

Pleomorphism and L cycles in CWD bacteria

The variety of variably acid-fast CWD bacterial forms reported in sarcoidosis all suggest a complex life cycle or "L cycle", as proposed by Mattman et al. for mycobacteria in 1960 [13]. The concept of a bacterial life cycle is controversial among traditional microbiologists, and is little known among medical clinicians. Traditionally, doctors have been taught that common bacteria primarily multiply by transverse fission; thus, the idea of a L cycle for CWD bacteria is indeed an alien microbiologic concept. However, the proposed microbiology of sarcoidosis is dependent on an appreciation of the varied growth forms that CWD microbes are capable of achieving, not only in the laboratory (in vitro) but also within the body (in vivo). For a review of the world literature concerning the pathogenicity and morphologic appearances of CWD forms, see Lida Mattman's Cell Wall Deficient Forms [14].

In general, pathologists search for acid-fast rod forms characteristic of the typical red-stained acid-fast rod forms of Mycobacterium tuberculosis to determine if acid-fast bacteria are present in sarcoidosis. However, the CWD organisms reported in vivo in sarcoid do not normally appear in that form. The Auramine-Rhodamine fluorescent test is yet another common microscopic screening test for mycobacteria, but according to Moscovic the CWD microbes in sarcoidosis do not fluoresce [3] .

The forms presented by Moscovic do not have the appearance of the acid-fast bacillary rod-forms characteristic of M. tuberculosis. Instead, round coccal forms can be identified in sarcoid that are similar in size to ordinary coccus forms of staphylococci. Other forms in vivo may appear larger (so-called "large bodies"); and some are much smaller approaching the limits of microscopic visibility. There is electron microscopic evidence that some of the tiniest forms are ultra-microscopic forms (approaching the size of viruses), which can pass through laboratory filters designed to hold back ordinary size bacteria. Filter-passing microbial forms are a hallmark of CWD bacteria. To be discussed later, the so-called "tuberculosis virus" is a filter-passing form of M. tuberculosis studied in the early decades of the twentieth century, and thought to be the etiologic agent of sarcoidosis by some experts in the bacteriology of tuberculosis.

The forms reported in sarcoid tissue in vivo by Cantwell are primarily in the round coccoid form. Such forms are best demonstrated by use of the acid-fast stain, traditionally used to demonstrate bacteria in TB and leprosy. Occasionally these forms can also be detected with Giemsa, Gram's staining for bacteria, and PAS staining for fungi.

Certain "intensified" acid-fast staining methods, specifically designed for the detection of CWD forms of mycobacteria, have been recommended by Mattman [15]. These intensified acid-fast stains, such as Alexander-Jackson's triple stain, may increase the acid-fast staining quality of the organisms to make them appear more red, pink, or magenta-colored against the blue background of acid-fast stained tissue [16]. The search for these tiny forms must be conducted at the highest magnification possible for the light microscope, namely a magnification of 1000X, using oil immersion.

Sarcoidosis and Nanobacteria

Yet another revolutionary and controversial finding in current microbiology is the recent interest in nanobacteria as a possible cause of disease of unknown etiology. Nanobacteria form a "bridge" between the tiniest sub-microscopic bacteria and the still smaller viruses. Nanobac Pharmaceuticals has a company web site which offers up-to-date research on these ultra-microscopic bacteria and their possible relationship to human pathology (http://www.nanobaclabs.com/Research/). Of great interest is the finding that the blood of all humans is infected with nanobacteria. This, of course, should rekindle interest in the role of bacteria in sarcoid, in cancer, and in other degenerative diseases.

At present, there is no research claiming an association between nanobacteria and sarcoid. However, nanobacteria may have some connection to the "tuberculosis virus" research of Sweany and others. Furthermore, nanobacteria are intimately connected with calcification; and "Schaumann's bodies" are laminated non-specific calcific inclusions often found in sarcoid granulomas. Recent research by Ang and Moscovic shows M.tuberculosis antigens in the immunoprofile of tissue Schaumann bodies. These investigators claim these bodies are remnants of "transformed tubercle bacilli" — and thus are a major clue to the etiology of sarcoidosis [17].

Propionibacteria in Sarcoidosis

In the late 1970s Homma et al. reported the frequent isolation of Propionibacterium acnes from biopsy specimens of sarcoid in Japanese patients [18]. In the 1980s Abe et al. isolated the same microbe from 31of 40 sarcoidal lymph nodes [19]. These Japanese researchers also cultured this organism from 38 of 180 non-sarcoidosis tissue specimens.

In 1999, Ishigi et al. found genomes of P. acnes in 12 of 15 patients with sarcoidosis. The three patients without P. acnes all had genomes of P. granulosum in their biopsy samples. It was concluded that propionibacteria are a likely cause of sarcoidosis, at least in Japan [20]. This is of importance because therapy with tetracyclines is not only a time-honored therapy for acne (associated with Propionibacterium acnes and Staphylococcus epidermidis) but is now being proposed as a controversial therapy for sarcoidosis.

In 2000 Ebe et al. also isolated genomes of propionibacteria from all their sarcoid patients. They claim a particular protein (RP 35) from P.acnes causes a cellular immune response in some sarcoidosis patients, but not in subjects without sarcoidosis [21]. In a Japanese-language review article of this work, entitled "Etiology of Sarcoidosis", Eishi concluded sarcoidosis may arise from one or more antigens of propionibacteria in an individual with a hereditary or acquired abnormality of the immune system [22].

Cryptic bacterial infection of the blood and sarcoidosis

If the microbiology of sarcoidosis were "simple", the bacterial cause would have been found decades ago. In my view, what makes the microbiology difficult to comprehend is that doctors tend to expect to find the same "specific" genus of bacterium in every sarcoid case, and also expect similar-appearing microbes in every case. In addition, physicians have been trained to downplay the significance of propionibacteria (such as P. acnes) and staphylococci (such as S. epidermidis) as common "skin contaminants" of no great etiologic significance in diseases like sarcoidosis and cancer. And, as already noted, the idea of certain bacteria having a "L cycle" is foreign to most physicians.

An even more difficult concept to conceive is the possible interconnectedness between different species of bacteria that has not been fully appreciated. For example, there is undoubtedly a close phylogenetic relationship between the acid-fast mycobacteria and the non-acid-fast propionibacteria (also known as corynebacteria and "diphtheroids"). And there is also a little-known but demonstrated phylogenetic connection between mycobacteria and non-acid-fast "micrococci" and even staphylococci.

Cantwell et al. cultured a Staphylococcus epidermidis from scleroderma that had unstable morphologic characteristics which vacillated between a pure coccus (Staphyloccus) and a cocco-bacillus (Corynebacterium-like or actinomycete-like microbe), depending on the lab media used to grow the bacteria[23] . Such transformation between two different genus species is generally considered "impossible" in bacteriology — and is often taken as a sign of laboratory "contamination." However, back in 1933, Novak and Henrici described a pleomorphic organism that also vacillated between two different species — one form was a pure coccus and the other form consisted of bacillary rod-like forms [24]. More details on this can be found in the paper by Cantwell et al [23] . It is important to keep an open mind regarding "fixed species" in microbiology, particularly in regard to occult bacterial and nanobacterial "infection" of human blood.

In a series of papers published in the 1970s, using the electron microscope and various testing procedures, an Italian team of researchers headed by Tedeschi showed that the erythrocytes (red blood cells) and the blood platelets of both normal and diseased patients are cryptically infected with pleomorphic bacteria. Electron-dense "granular bodies" were found within the erythrocytes, and a variety of microbial forms and species were cultured and reported as mycoplasma-like and corynebacteria-like L-forms of bacteria, Staphylococcus epidermidis, micrococci, cocci, and cocco-bacillary forms [25, 26].

The idea that blood contains bacteria has been repeatedly raised by various (and controversial) cancer microbe researchers for decades. But the idea was never taken seriously because bacteria grown from cancer patients were never considered to represent anything more than a hodgepodge of inconsequential and contaminating bacteria like staph, strep, and various other common bacilli of no etiologic significance. The variety of different species of pleomorphic bacteria recovered from various forms of cancer (and sarcoid) makes physicians highly dubious about a specific bona fide cancer microbe.

Some of Tedeschi's microbes were acid-fast [26], a staining quality characteristic of Wuerthele-Caspe Livingston's "cancer microbe" [27, 28], and also a characteristic of CWD bacteria observed in sarcoidosis. Tedeschi's team also suggested the evolution of cocci and diphtheroids (i.e. corynebacteria and propionibacteria) taking origin from cell-wall-deficient forms seems not to be related to a particular state of illness, but to be the consequence of a generalized crypto-infection.

All of this indicates that human blood is definitely not sterile, and should raise suspicion that these tiny blood bacteria could be involved in the production of a disease like sarcoidosis, as well as other inflammatory and neoplastic diseases.

A more recent study entitled "Are there naturally occurring
pleomorphic bacteria in the blood of healthy humans?", by McLaughlin and associates in the Journal of Clinical Microbiology (December 2002), confirms the presence of a wide diversity of microorganisms within the blood of healthy people [29]. Another study designed to culture CWD bacteria from the blood by Brown et al. concluded that 38% of sarcoid cases and 41% of control subjects were positive for these CWD forms [30]. And with new research showing frequent nanobacteria in the blood, it is apparent there is much to learn about human blood and what microbes it contains normally and what it contains in disease.
As they have done for a century, microbiologists will undoubtedly quibble about what to name these organisms. But what is much more important than determining a species name is to determine what an organism "does"— not only in the laboratory, but also within the human body. What allows these microbes to exist in harmony with us? And what turns them into killers?

Filterable and granular forms of tuberculosis mycobacteria

Although physicians and histopathologists are trained to recognize the well-known acid-fast rod forms of the tubercle bacillus (M. tuberculosis), they apparently have little knowledge or interest in the non-acid-fast CWD forms of this microbe. It is most important in the microbiology of sarcoidosis to recognize that the "classic" acid-fast rod form of the tubercle bacillus is not the only manifestation of the etiologic agent of tuberculosis.

To more fully understand the various growth forms of acid-fast mycobacteria, it is not only necessary to consider the "filterable" forms of these organisms, as well as the function of the TB "granules," but also to have some appreciation of the fungal origin of the mycobacteria. It is well known in microbiology that the acid-fast mycobacteria are phylogenetically a bridge between the "higher" plant-like fungi and the "lower" bacteria. "Myco" in Greek means fungus; ergo — the mycobacteria.

In the earlier decades of the twentieth century, sarcoidosis was known as "lymphogranulomatosis benigna" and later as "Schaumann's disease. Schaumann and Hallberg, along with other Swedish researchers like Gullberg, and Hollstrom, were all aware that a postulated origin of the TB microbe was from a pleomorphic "fungus of yeast odium type" [31-33]. Prolonged and intensive microbiologic study of single-cell cultures of this fungus revealed a complex microbe with the ability to produce growth forms which were quite unlike the "classic" acid-fast rod-form of the TB germ.

For example, Hollstrom [33] mentions growth forms of the tubercle bacillus consisting of "an ovoid fungus cell", "an almost invisible powder", as well as "cocciform organisms, diphtheroids [such as propionibacteria and corynebacteria], and the classic "acid-fast rods of tubercle bacillus type." All this has bearing on the little-studied pleomorphic forms in sarcoidosis in vivo presented by Moscovic, and by Cantwell in this report.

As mentioned over and over, sarcoidosis has always been a disease considered to be closely related to tuberculosis, even though an infectious element in this disease has never been demonstrated to the satisfaction of the experts in sarcoid. However, the "proof" required by scientists seems to require the demonstration of acid-fast bacteria similar to M. tuberculosis in sarcoidosis. In my view, this proof is unreasonable and unsound because there are other valid growth forms of the tubercle bacillus which have been ignored or overlooked in an attempt to uncover an infectious etiology of sarcoidosis (as well as an infectious etiology of some forms of cancer).

Sweany, in two papers published in the American Review of Tuberculosis in 1928, entitled "The granules of the tubercle bacillus" and "The filterabillity of the tubercle bacillus", explains the many growth forms of this microbe, as well as their ability to produce pathologic changes when inoculated into guinea pigs [34,35]. This work is undoubtedly related to current findings of pleomorphic CWD mycobacteria.

In summarizing the various unusual growth forms of M. tuberculosis known to bacteriologists since the late nineteenth century, Sweeney notes non-acid-fast granules, zooglear forms, small globoid bodies, endospores developing into coccoid forms which further develop into bacilli, the deterioration of forms into saprophytic microorganisms with coccoid, bacillary, and "diphtheroid" and staphylococcal morphology, and much more [34].

After extensive animal experimentation with these "variant" forms, Sweany remarks: "During the process there seems to be a stimulation of the lymphoid tissue in the lungs and a progressive action on the reticuloendothelial elements…approaching gradually the more typical anatomical formations of tuberculosis. This fact alone proves that some of the filterable forms are not tubercle bacilli, yet they possess sufficient intrinsic quality to regenerate tubercle bacilli on passage. It suggests a relationship to lymphogranuloma (i.e sarcoidosis)." [35]

Sweany stresses that "all living microscopic forms of life undergo variations in their development," and "there is a vast difference between the changes on artificial [laboratory] media and those in the animal body." Furthermore, "any series of observations of tubercle microorganisms in the animal body will reveal the presence of many changes apart from the acid-fast stage. The changes are not alike in any two animals, or, in fact, in any two organs." Lastly, Sweany was the first to note "non-acid-fast coccoids", similar to ordinary staphylococci as a variant growth form of M. tuberculosis [34].

Unfortunately, in the search for a bacteriologic agent in sarcoid, modern researchers have largely ignored Sweany's admonition that "the most common acid-fast bacillary form of the tubercle bacillus is not the only manifestation of the etiologic agent of tuberculosis." [34] And much of this "old" sarcoid bacteriology from the last century seems forgotten in the current search for a non-microbial cause of sarcoidosis.

One possible reason for lack of interest in the proposed microbiology of sarcoid is the view that such microbes are difficult to detect in sarcoid tissue. In my experience, it is not difficult to detect microbes as long as one is willing to patiently search (with special stains and under oil immersion) for microbiologic forms characteristic of CWD bacteria. It would be most helpful if more physicians and microbiologists would confirm (or deny) the presence of microbes in vivo in sarcoid.

At present, it seems foolish to argue what to "call" these microbes. More important is to first have more agreement as to whether these CWD forms exist or do not exist in vivo. After this is accomplished, investigators can argue and quibble about exactly what type of species of microbes are involved in sarcoid, and whether there is just one type of microbe or multiple species involved in the etiology.

In my view, it is best to keep an open mind and to consider all bacterial isolates from sarcoid as possible suspects, particularly if similar-sized forms are observed in vivo within the affected tissue. In several unreported cases, we were able to culture staphylococci and corynebacteria from skin lesions of sarcoid. Ordinarily, these would be quickly dismissed as "contaminants". However, the coccus forms observed in culture in vitro were similar and shape to those coccoid forms seen in vivo in the affected sarcoid tissue sections, as noted in Case One below.

Antibiotic Therapy for Sarcoidosis

The currently accepted therapy for sarcoidosis remains immunosuppressive and cytotoxic drugs and long term corticosteroids. In 1982 his frequent finding of bacteria in sarcoid-damaged tissue prompted Moscovic to suggest tetracycline therapy as treatment [3]. Noting the undesirable effect of long term steroids, he speculated that "tetracyclines (or similar agents with a potential effect on protein synthesis in L-forms) may be expected to be clinically effective, and their use in sarcoidosis should be investigated."

In 2001 a team of French dermatologists headed by Bachelez et al. reported an improvement in 10 of 12 patients with cutaneous sarcoidosis by use of minocycline and doxycycline [36]. More clinical studies like this are sorely needed to evaluate antibiotics and different antibiotic combinations for sarcoidosis. Most likely prolonged combination antibiotic therapy will be needed for sarcoid, as is required for the proper therapy of tuberculosis.

Histopathologic findings of bacteria in 5 Sarcoid cases

In this report a series of 22 color and 6 black/white photos are presented as evidence of CWD microbes in histopathologic material taken from biopsy of four confirmed cases of sarcoidosis and one case of sarcoid-like granulomas with coexistent malignant lymphocytic lymphoma (cancer).

Case 1: A white female developed uveitis progressing to blindness at age 41. At age 51 a carcinoma of the lung was suspected, but a resection of the lower lobe of the right lung revealed sarcoidosis. At age 54, she developed an area of skin hardness on the medial aspect of the right leg. A skin biopsy revealed epithelioid granulomas in the deep dermis, consistent with sarcoidosis of the skin. Further details of this patient are recorded in a case report published in Dermatologica [7].

Case 2: A 47 year-old black woman developed enlarged cervical lymph nodes, cough, dyspnea and fatigue. A roentgenogram of the chest revealed pulmonary fibrosis. Microscopic sections of an enlarged left scalene node revealed non-caseating granulomas, consistent with the diagnosis of sarcoidosis. Further details of this case are reported as "Case 1" in Growth [8].

Case 3: A 25 year-old white man was diagnosed with systemic sarcoidosis with paratracheal and hilar adenopathy and bilateral upper lobe infiltrates. Several subaortic lymph nodes showed granulomatous changes consistent with sarcoidosis. At age 31 he developed skin nodules on the right elbow consistent with sarcoidosis. More details of this case are reported as "Case 3" in Growth [8] .

Case 4: A 39 year-old black woman became developed multiple lesion of cutaneous sarcoidosis of the face, which progressed rapidly with severe disfiguration. At age 53 there was evidence of sarcoidosis in the larynx, lungs, and bones. At this time, a skin biopsy of a facial lesion also revealed sarcoidosis. More details of this case appear as "Case 2" in Growth [8].

Case 5: A 72 year-old white woman developed a nodular skin lesion of the right eyebrow and an additional lesion in the right pre-auricular area. Biopsy of both revealed changes consistent with sarcoidosis. The following year she experienced fever and chills, and a roentgenogram of the chest showed bilateral infiltrates. A biopsy was performed of enlarged right scalene lymph nodes. Histopathologic examination of this material revealed lymphocytic lymphoma. Chemotherapy was initiated for lymphoma, which resulted in temporary improvement. Further details of this case of sarcoid and associated lymphoma are reported as a case report in the International Journal of Dermatology [9].

Conclusions

There is abundant evidence, some dating back to the 1930s and 1940s by various investigators (such as Gullberg, Hollstrom, Schaumann, and others) 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."

In view of the possible efficacy of tetracyclines in the treatment of sarcoidosis, it is imperative that attention be paid to histopathologic findings of CWD bacteria (or variant growth forms of M. tuberculosis and the phylogenetically-related propionobacteria) in this disease. Failure to take this research seriously can only be regarded as a rejection of bona fide scientific research and an uncaring attitude toward sarcoid sufferers.

The purpose of this report is to stimulate further tissue investigations for bacteria of this type in sarcoidosis, and to give encouragement to those sarcoid patients who wish to experiment with antibiotic regimens that might ameliorate signs and symptoms of sarcoidosis due to unrecognized infection with sarcoid-associated CWD bacteria.

Hopefully, this report will rekindle interest in the century-old microbiology of sarcoid — and serve as a guide to histopathologists examining sarcoid tissue for the presence of bacteria.

Legend for Color Photographs


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1: Sarcoidosis of the lung. In center, a collection of magenta-colored coccoid forms. (Case 1; Alexander-Jackson [acid-fast] triple stain, magnification x1000, in oil.)


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2: Sarcoidosis of the lung. A collection of tighty-packed coccoid forms. (Case 1; Giemsa stain, magnification x1000, in oil.)


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3. Sarcoidosis of the lung. In center, a large collection of larger coccoid forms, some of which are clear and some crescent-shaped. These forms are typical of "large body" formations of CWD bacteria. (Case 1; Goodpasture-MacCallum [Gram] stain, magnification x1000, in oil.)


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4. Sarcoidosis of the lung. A rare focus of PAS-positive, pink and purple coccoid forms. (Case 1; PAS stain [for fungus], magnification x1000, in oil.)


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5. Sarcoidosis of the lung. Same section as Fig. 4. Note the variably sized and variably-staining pink and purple forms, some of which are clear. (Case 1; PAS stain [for fungus], magnification x1000, in oil.)


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6. Sarcoidosis of the lung. In center, a focus of basophilic forms seen with "routine" hematoxylin-eosin stain, as used by all pathologists. (Case 1; Hematoxylin-eosin stain, magnification x1000, in oil.)


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7. Sarcoidosis of the skin. A large collection of purple staining coccoid forms in the deep dermis between two granulomas. These forms are not seen within the granuloma. (Case 1; Intensified Kinyoun's [acid-fast] stain, magnification x 1000, in oil.)


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8. Sarcoidosis of the skin. A collection of purple-stained coccoid forms in the deep dermis. (Case 1; Ziehl-Neelsen [acid-fast] stain, magnification x1000, in oil.)


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9. Smear from growth in thioglycollate broth culture of sarcoidosis of the skin showing Staphylococcus epidermidis. Note the unusual tiny rod-shaped organism emanating (?) from a collection of cocci in the center of the photo. Compare the size and shape of these staphylococci to the coccoid forms seen in vivo in the skin and lung sarcoid lesions. (Case 1; Gram' stain, magnification x1000, in oil.)


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10. Additional photo of smear of S. epidermidis cultured from sarcoidosis of the skin. (Case 1; Gram' stain, magnification x1000, in oil.)


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11. Smear of acid-fast stained S. epidermidis cultured from sarcoidosis of the skin. Compare the size and shape with the coccoid forms in the skin in the acid-fast stained tissue sections shown in Figs. 7 and 8. (Case 1; Ziehl-Neelsen [acid-fast] stain, magnification x1000, in oil.)


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12. Sarcoidosis of the lymph node. Three clumps of tightly-packed coccoid forms inside an affected lymph node. (Case 2; Intensified Kinyoun's [acid-fast] stain, magnification x1000, in oil.)


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13. Sarcoidosis of the lymph node. Same section as Fig. 12 showing a collection of coccoid forms at the edge of the gland in the connective tissue. (Case 2; Intensified Kinyoun's [acid-fast] stain, magnification x1000, in oil.)


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14. Sarcoidosis of the skin. Several coccoid forms in center in a granulomatous area of the mid-dermis. (Case 3; Intensified Kinyoun's [acid-fast] stain, magnification x1000, in oil.)


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15. Sarcoidosis of the skin. Same section of Fig. 14 showing larger coccoid forms in center of photo. (Case 3; Intensified Kinyoun's [acid-fast] stain, magnification x1000, in oil.)


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16. Sarcoidosis of the skin. In center, variably sized coccoid forms in the mid-dermis. (Case 4; Intensified Kinyoun's [acid-fast] stain, magnification x1000, in oil.)


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17. Sarcoidosis of the skin. In center, coccoid forms plus a much larger "large body" in the deep dermis in a granulomatous area. (Case 4; Intensified Kinyoun's [acid-fast] stain, magnification x1000, in oil.)


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18. Sarcoid-like granuloma of the skin. Purple-staining coccoid forms right of center in granulomatous area of the upper dermis. (Case 5; Goodpasture-MacCallum [Gram's] stain, magnification x1000, in oil.)


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19. Sarcoid-like granuloma of the skin. Eosinophilic (pink) and basophilic (purple) coccoid forms in the upper dermis at the dermal-epidermal junction identified in "routine" staining method universally used by pathologists. (Case 5; Hematoxylin-eosin stain, magnification x1000, in oil.)


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20. Lymphocytic lymphoma of a lymph node in a patient with sarcoid-like granuloma. In center, a tightly-packed focus of purple-staining coccoid forms. (Case 5; Intensified Kinyoun's [acid-fast] stain, magnification x1000, in oil.)


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21. Lymphocytic lymphoma of a lymph node in a patient with sarcoid-like granulomas. In center, a very rare tiny focus of four magenta-colored coccoid forms within the node. (Case 5; Alexander-Jackson [acid-fast] triple stain, magnification x1000, in oil.)


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22. Lymphocytic lymphoma of a lymph node in a patient with sarcoid-like granulomas. In center, intracellular weakly acid-fast coccoid forms. Note the acid-fast spicule (rod-form?) emanating from the cell at the 4 o'clock position. (Case 5; Intensified Kinyoun's [acid-fast] stain, magnification x1000, in oil.)

Legend for Black and White Photos


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1. Sarcoidosis of the lung. In center, a focus of variably-sized acid-fast coccoid forms. (Case 1; Intensified Kinyoun's [acid-fast] stain, magnification x1000, in oil.)


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2. Sarcoidosis of the lung. In center area, larger, variably-sized round forms, suggestive of "large bodies". Some of the forms are clear, resembling "ghost forms". (Case 1; Goodpasture-MacCallum stain, magnification x1000, in oil.)


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3. Sarcoidosis of the lung. In center, an area containing still larger giant "large body" forms in center. Large bodies are a characteristic of CWD bacteria. (Case 1; Goodpasture-MacCallum stain, magnification x1000, in oil.)


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4. Sarcoidosis of the lung. In center, a "large body" with internal vacuolar structures, characteristic of CWD bacteria. (Case 1; Alexander-Jackson triple stain, magnification x1000, in oil.)


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5. Smear from thioglycollate culture of sarcoidosis of the skin identified as Gram-positive Staphlyococcus epidermidis. In center, note "rod-like" forms emanating(?) from a small group of cocci. Compare size and shape of these cocci with similar-sized coccoid forms seen in in vivo in lung in Fig. 1. (Case 1; Gram's stain, magnification x1000, in oil.)


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6. Smear from same culture as Fig 5, showing appearance of S. epidermidis cocci stained with as acid-fast stain. Compare size and shape of these cocci with similar-sized coccoid forms seen in vivo in lung in Fig. 1. (Case 1; Ziehl-Neelsen stain, magnification x1000, in oil.)


References:

1. Judge MS, Mattman LH: Cell wall-deficient mycobacteria in tuberculosis, sarcoidosis, and leprosy. In, Domingue GJ (Ed), Cell Wall-Deficient Bacteria. 1982 Addison-Wesley, Reading, pp 257-298

2. Moscovic EA: Sarcoidosis and mycobacterial L-forms. A critical reappraisal of pleomorphic chromogenic bodies (Hamazaki corpuscles) in lymph nodes. Pathol Annu. 1978;13 Pt 2:69-164

3. Moscovic EA: Sarcoidosis and mycobacterial L-forms: Histologic studies. In, Domingue GJ (Ed), Cell Wall-Deficient Bacteria. 1982 Addison-Wesley, Reading, pp 299-320

4. Karakantza M, Matutes E, MacLennan K, O'Connor NT, Srivastava PC, Catovsky D: Association between sarcoidosis and lymphoma revisited. J Clin Pathol. 1996 Mar;49(3):208-12

5. Alavi HA, Moscovic EA: Immunolocalization of cell-wall-deficient forms of Mycobacterium tuberculosis complex in sarcoidosis and in sinus histiocytosis of lymph nodes draining carcinoma. Histol Histopathol. 1996 Jul;11(3):683-94

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(C)Copyright 2003 Alan R Cantwell, Jr., M.D.


 
 Re: Bacteria in Sarcoidosis, and a Rationale for Antibiotic Therapy in this Disease
Author: Friedrich Flachsbart (---.dip.t-dialin.net)
Date:   10-14-03 12:27

FORMAL PEER-REVIEW ASSESSMENT
REVIEWERS NAME: Friedrich Flachsbart MD, Göttingen, Germany
REVIEW QUALIFICATIONS: 2 or more papers in PubMed
COMPETING INTERESTS: none declared

Dear Sir,
The microbial world is extremely complex.

Corynebacterium glutamicum showed mutants with altered cell wall lipid composition.

In specific circumstances the mutants lack major glycolipids in their cell wall lipid fraction.

A dramatic altered cell wall lipid bilayer is the consequence. (1)

Mutants like these are able to induce human reactions like sarcoidosis.

We have to learn more about the microbes and their interaction with man.

Therefore I believe this paper of A. Cantwell is a very important wake-up call to the scientific community.


1. Tzvetkov M, Klopprogge C, Zelder O, Liebl W:
Genetic dissection of trehalose biosynthesis in Corynebacterium glutamicum: inactivation of trehalose production leads to impaired growth and an altered cell wall lipid composition.
Microbiology 2003;149:1659-1673

 
 Re:
Author: ggauthier (---.w83-193.abo.wanadoo.fr)
Date:   03-01-05 02:17

Bonjour je suis l'auteur d'un site francais sur la sarcoidose et nous faisons partis d'une associaiton Reseau International de Saoutien des Malades de la Sarcoidose" et dont le Pf Valeyre s'en occupe, j'aimerai savoir si vous accepteriez de publier vos pages sur notre mediawiki qui est ouvert a tous medecins et malades et j'ai creer des pages multilangues pour cela, si ce n'est pas possible puis je citer votre site par un lien.
En vous remerciant ggauthier

adresse wiki: http://www.combbs.net ; future adresse dans 48h http://sarcoidose-infos.com

traductin faite avec google linguistique.

Hello I am the author of a French site on the sarcoidose and we make parties of a associaiton International Reseau of Saoutien of the Patients of Sarcoidose "and of which the PF Valeyre is occupied some, I will like to know if you would agree to publish your pages on our mediawiki which is open A all doctors and patients and I have creer multilangues pages for that, if it is not possible then I to quote your site by a bond. Trevol Marshall of sarinfos.com has to authorize us to use the texts of course by sitant them. By thanking you ggauthier addresses wiki: http://www.combbs.net; future address in 48h http://sarcoidose-infos.com

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