Exploring the association between Morgellons disease and Lyme disease: identification of Borrelia burgdorferi in Morgellons disease patients
Marianne J Middelveen1, Cheryl Bandoski2, Jennie Burke3, Eva Sapi2, Katherine R Filush2, Yean Wang3, Agustin Franco3, Peter J Mayne1 and Raphael B Stricker14*

http://www.biomedcentral.com/1471-5945/15/1

Highlights:

Methods & Results

Based on culture, histology, immunohistochemistry, electron microscopy and molecular testing, we present corroborating evidence of spirochetal infection in a larger group of 25 MD patients. Irrespective of Lyme serological reactivity, all patients in our study group demonstrated histological evidence of epithelial spirochetal infection. Strength of evidence based on other testing varied among patients. Spirochetes identified as Borrelia strains by polymerase chain reaction (PCR) and/or in-situ DNA hybridization were detected in 24/25 of our study patients. Skin cultures containing Borrelia spirochetes were obtained from four patients, thus demonstrating that the organisms present in dermatological specimens were viable. Spirochetes identified by PCR asBorrelia burgdorferi were cultured from blood in seven patients and from vaginal secretions in three patients, demonstrating systemic infection. Based on these observations, a clinical classification system for MD is proposed.

Conclusions

Our study using multiple detection methods confirms that MD is a true somatic illness associated with Borrelia spirochetes that cause Lyme disease. Further studies are needed to determine the optimal treatment for this spirochete-associated dermopathy.

Fiber Construction/ absense of parasites and fungi:

 All histological sections were examined at 400X and 1000X magnification. In slides stained with Dieterle silver nitrate stain and/or anti-Bb antibodies, sectioned filaments embedded in epithelial cells were observed in samples of all callus material and in the biopsy material from patient 24. All filaments demonstrated the same morphology: a hollow medulla surrounded by a solid cortex. Filamentous material demonstrated no characteristics consistent with fungal elements such as hyphae, or any characteristics of known parasites such as microfilariae.

Presence of Bb in vaginal cultures:

Vaginal culture

Swabs of vaginal secretions were submitted for culture from patients 8, 14, 21 and 24. Motile bacteria were visible in culture fluid from all four patients. Staining of vaginal cultures concentrated by centrifugation followed by Dieterle silver nitrate staining and anti-Bb immunostaining was performed for specimens taken from patients 8 and 21. Both specimens demonstrated positive staining of both spherules and spirochetes consistent with morphological forms of Borrelia with Dieterle silver nitrate stain. Both specimens demonstrated strongly positive Bb immunostaining of the bacteria in the samples as well as the surrounding cellular debris, as described above. Data is summarized in Table 3.

 Lyme testing and Trepenoma Denticola:

A. PCR Detection of Borrelia

Various sample types from 20 patients were submitted for PCR detection of Borrelia at three independent laboratories. These samples included whole dermatological calluses, histological skin sections, skin culture, blood culture, vaginal cultures, and one specimen of intestinal epithelial tissue that had sloughed off in the patient’s feces during an intestinal cleanse. Borrelia genes were detected in 18 of the patients whose samples were submitted, and results were equivocal for 2 patients. Amplicon sequences consistent with Borrelia DNA were obtained for the PCR products from 14 patients. Bb sensu stricto sequence was confirmed in 12 patients, while patient 23 was found to have an amplicon sequence consistent with B. miyamotoi and patient 24 had a sequence consistent with B. garinii. The latter patient had contracted Lyme disease in Europe. Positive PCR results are summarized in Table 4.

Table 4. Detection ofBorreliaDNA by PCR in samples derived from Morgellons patients

Skin cultures from patients 6, 9, 13 and 21 were subjected to PCR testing, and three of the four samples tested positive, confirming the presence of Borrelia in the cultures. The fourth culture sample (patient 21) had equivocal PCR testing using the 16S rRNA probe but tested positive using the FlaB molecular probe (see below). Thus molecular testing confirmed the presence of viableBorrelia spirochetes in all four skin culture samples.

Treponema denticola was detected in 5/16 scab/callus samples sent to Australian Biologics. T. denticola was not detected in any blood, skin or vaginal cultures (data not shown).

Colored fibers:

 As with BDD, MD filaments are not textile fibers. MD fibers are biofilaments of human cellular origin produced by epithelial cells and stemming from deeper layers of the epidermis and the root sheath of hair follicles [5],[9]. Immunohistochemical and histological staining has demonstrated that these multicolored filaments are composed of collagen and keratin [6],[9]. They are nucleated at the base of attachment to adjacent epithelial cells, and the cells at the filament base are continuous in appearance with the surrounding skin cells [6]. Although the cause of coloration of red fibers has not been defined, the blue coloration is the result of melanin pigmentation rather than a dye, as shown by Fontana Masson histological staining [6]. There are no known textile fibers that are collagen in composition, nucleated at their base of attachment, or pigmented blue with melanin. Thus the characteristic fibers in MD are clearly distinct from textile fibers [6].

Syphillis Comparisons:

 Lyme borreliosis is a systemic infection that is commonly associated with dermatological manifestations [35]. Given that most MD patients are serologically reactive to Bb antigens, the presence of Lyme spirochetes in MD dermatological lesions is predictable and supports an etiologic role of the spirochetal disease. Bb sensu stricto and Bb sensu lato have been associated with numerous dermatological manifestations including erythema migrans, borrelial lymphocytoma, acrodermatitis chronica atrophicans, morphea, lichen sclerosus, cutaneous B-cell lymphoma, scleroderma, lymphadenosis cutis and prurigo pigmentosa [35]-[38]. Likewise it appears that MD is associated with Lyme disease in a subgroup of patients with this spirochetal illness [6]-[8]. It is possible that spirochetes other than Bb sensu stricto and the Bb sensu lato complex, such as the agent of syphilis, Treponema pallidum, could be responsible for similar manifestations in other patients. In support of this supposition, Ekbom’s original 1945 description of delusions of parasitosis reported that many of the patients in that study were diagnosed with syphilis, thus linking treponemal infection with pruritus, crawling sensations and belief of infestation [39]. Furthermore, treponemal spirochetes have been shown to induce the formation of filamentous lesions in animal models [26]-[30].

 Lyme coinfections:

Although spirochetes appear to be the primary etiologic agents of MD, evidence suggests that the etiology is multifactorial. Secondary etiologic factors, such as female predominance, immune dysfunction, and other tickborne coinfections appear to play a role in the development of this dermopathy [1]-[5]. As noted in Table 1, we found serological evidence of tickborne coinfections including Babesia, Anaplasma, Ehrlichia, Bartonella and Rickettsia spp. in five of six patients who were tested. The role of these coinfections in MD remains undefined. Although we demonstrated the presence of Borrelia spirochetes in all of the patients in our study group, T. denticola was detected in dermatological specimens from five patients. The role of these commonly occurring oral spirochetes in the evolution of MD dermatological lesions and subsequent filament formation is uncertain, and we speculate that coinvolvement of these and perhaps other pathogens could be contributing or exacerbating factors in MD.

A study from the Centers for Disease Control and Prevention (CDC) concluded that pathogens were not involved in MD [22]. The search for spirochetal pathogens in that study was limited to Warthin-Starry staining on a small number of tissue samples and commercial two-tiered serological Lyme disease testing as interpreted by the CDC Lyme surveillance criteria [22]. It should be noted that only two of the patients in our study group were positive for Lyme disease based on the CDC Lyme surveillance criteria and yet Borrelia spirochetes were readily detectable in this group of 25 MD patients.

 Proposed MD classification scale:

Based on our experience with several hundred MD patients, we propose a clinical classification scheme that reflects the duration and location of MD lesions, as follows:

1. Early localized: lesions/fibers present for less than three (3) months and localized to one area of the body (head, trunk, extremities).

2. Early disseminated: lesions/fibers present for less than three (3) months and involving more than one area of the body (head, trunk, extremities).

3. Late localized: lesions/fibers present for more than six (6) months and localized to one area of the body (head, trunk, extremities).

4. Late disseminated: lesions/fibers present for more than six (6) months and involving more than one area of the body (head, trunk, extremities).

 Hope it's OK for me to paste so much of this article here. I'm anxious to hear reactions from the CZ Morgie community.