Exploring the Association Between Morgellons Disease and Lyme Disease

Identification of Borrelia Burgdorferi in Morgellons Disease Patients

Marianne J Middelveen; Cheryl Bandoski; Jennie Burke; Eva Sapi; Katherine R Filush; Yean Wang; Agustin Franco; Peter J Mayne; Raphael B Stricker

Disclosures

BMC Dermatol. 2015;15(1)

Abstract and Introduction

Abstract

Background Morgellons disease (MD) is a complex skin disorder characterized by ulcerating lesions that have protruding or embedded filaments. Many clinicians refer to this condition as delusional parasitosis or delusional infestation and consider the filaments to be introduced textile fibers. In contrast, recent studies indicate that MD is a true somatic illness associated with tickborne infection, that the filaments are keratin and collagen in composition and that they result from proliferation and activation of keratinocytes and fibroblasts in the skin. Previously, spirochetes have been detected in the dermatological specimens from four MD patients, thus providing evidence of an infectious process.

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 as Borrelia 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.

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Abstract and Introduction
Background
Methods
Results
Discussion
Conclusions
References

Table 1. Clinical data for study patients
Patient #	Age	Gender	Lyme serology	Coinfecting tickborne diseases	Antibiotic treatment
1	86	Female	Positive	Babesia microti, Bartonella henselae	Treated at time of sampling
2	52	Female	Positive	Ehrlichia chaffeensis, Anaplasma phagocytophilum	Previous treatment, but off at time of study
3	56	Female	*Positive	Not tested	Never treated
4	75	Female	*Positive	Not tested	Not treated at time of study
5	50	Male	Equivocal	Not tested	Never treated
6	41	Male	Positive	Spotted fever group and typhus fever group	Began treatment after start of study
7	51	Female	*Positive	Not tested	Never treated
8	53	Female	Positive	Not tested	Previous treatment, but off at time of study
9	35	Female	Not tested	Not tested	Never treated
10	63	Female	Positive	Spotted fever group and Mycoplasma spp. (Labcorp)	Not treated at time of study
11	47	Female	*Positive	Not tested	Not treated at time of study
12	38	Male	Positive	None	On antibiotic therapy during study
13	43	Female	Positive	Babesia spp.	Treated but off antibiotics during study
14	53	Female	*Positive	Not tested	Never treated
15	48	Female	Clinical diagnosis, not tested	Not tested	Not treated at time of study
16	56	Female	Not tested	Not tested	Never treated
17	62	Female	*Positive	Not tested	Not treated at time of study
18	51	Female	Not tested	Not tested	Never treated
19	75	Female	**Positive	Not tested	Had 2 weeks treatment for Lyme but no treatment after
20	60	Female	**Positive	Not tested	Had 3 weeks erythromycin after EM rash and + serology, no treatment after
21	37	Female	Positive	Not tested	Not treated at time of study
22	53	Female	Not tested	Not tested	Not treated at time of study
23	68	Female	Not tested	Not tested	Never treated
24	73	Female	Not tested	Not tested	Never treated
25	58	Female	***Positive	Not tested	Never treated

All Lyme serology except that of patients 19, 20, and 25 tested and interpreted by IGeneX Reference Laboratories, Palo Alto, CA [10].
*Tested for B. burgdorferi after skin sampling was taken for study.
**Positive by 2-tiered CDC surveillance criteria.
***Tested by Spectracell Laboratories, Houston, TX.

Table 2. Microscopic examination of dermatological tissue sections with Dieterle or Warthin Starry silver nitrate stain and anti-Bb polyclonal immunostain
Patient #	Dieterle	Bb-polyclonal immunostain	Filaments morphologically consistent with MD
1	Spirochetes observed	*Positive	Detected
2	Spirochetes observed	*Positive	Detected
3	Spirochetes observed	*Positive	Detected
4	Spirochetes observed	*Positive	Detected
5	Spirochetes not observed	**Positive	Detected
8	Spirochetes observed	Positive	Detected
10	Spirochetes observed	Positive	Detected
11	Spirochetes observed	Positive	Detected
12	Spirochetes observed	Positive	Detected
13	Spirochetes observed	Positive	Detected
15	Spirochetes observed	Positive	Detected
16	Spirochetes observed	Positive	Detected
18	Spirochetes observed	Positive	Detected
19	Spirochetes observed	Positive	Detected
20	Spirochetes observed	Positive	Detected
22	Spirochetes observed	Positive	Detected
23	Spirochetes observed	Positive	Detected
24	Spherules consistent with Bb morphological variants observed	Positive	Detected
25	Spirochetes observed	Positive	Detected

Dieterle and or Warthin-Starry silver nitrate staining performed at Interscope Laboratories, Los Angeles, CA, and or McClain Laboratories, Smithtown, NY.
Bb polyclonal immunostaining performed at McClain Laboratories.
*Polyclonal Bb immunostaining performed at University of New Haven, West Haven, CT and McClain Laboratories.
**Sectioned specimen consisted of hair follicular bulbs with attached root sheaths rather than skin. Polyclonal Bb immunostaining performed at the University of New Haven.

Table 3. Microscopic examination of sectioned culture pellets with Dieterle or Warthin Starry silver nitrate stain and anti-Bb polyclonal immunostain
Patient #	Inoculum type	Culture fluid	Dieterle	Bb polyclonal immunostain*
3	Skin	Motile spirochetes	Spirochetes	Positive**
3	Blood	Motile bacteria	Spirochetes	Positive
4	Skin	Motile spirochetes	Not submitted	Not submitted
4	Blood	Motile bacteria	Not submitted	Not submitted
6	Skin***	Little growth observed	Spirochetes	Positive
7	Blood	Spherules	Spherules	Positive
8	Blood	Spherules	Spirochetes	Positive
8	Vaginal	Motile spherules	Spherules	Positive
9	Skin	Little growth, single long motile spirochete	Not submitted	Not submitted
13	Skin	Spherules/motile elongated bacteria	Spirochetes/spherules	Positive
13	Blood	Spherules	Spirochetes/spherules	Positive
14	Blood	Spherules	Not submitted	Not submitted
14	Vaginal	Motile spirochetes	Not submitted	Not submitted
17	Blood	Spherules	Spirochetes/spherules	Positive
21	Skin	Spherules/spirochetes	Not submitted	Not submitted
21	Vaginal	Motile spherules	Spherules	Positive
24	Blood	Spherules/Motile bacteria	Not submitted	Not submitted
24	Vaginal	Motile spirochetes	Not submitted	Not submitted

*Anti-Bb immunostaining performed at McClain Laboratory, Smithtown, NY, except for the skin culture from patient 3.
**Anti-Bb immunostaining performed at the University of New Haven, West Haven, CT.
***SEM revealed well-defined spirochetes with periplasmic flagella.

Table 4. Detection of Borrelia DNA by PCR in samples derived from Morgellons patients
#	Specimen	PCR University of New Haven	PCR Australian Biologics	Sequencing
1	Whole callus	pyrG, fla, ospC	16S rRNA	pyrG, fla, ospC
2	Whole callus	pyrG, fla, 16S rRNA	16S rRNA	pyrG
3	Whole callus	fla, pyrG, 16S rRNA, uvrA, ospC	16S rRNA	16S RNA, pyrG, fla, uvrA, ospC
3	Blood culture	fla
4	Callus section	16S rRNA
4	Blood culture	fla
5	Whole callus	pyrG	16S rRNA	pyrG
6	Skin culture	16S rRNA
7	Blood culture	fla
8	Whole callus	pyrG, 16S rRNA, fla		pyrG, fla,
8	Blood culture	fla, pyrG		fla
9	Skin culture	fla		fla
10	Whole callus	16S rRNA, pyrG, fla	16S rRNA	16S rRNA, pyrG
10	Intestinal specimen		16S rRNA
11	Whole callus	fla+/- indeterminate	Inhibited
13	Whole callus	uvrA		uvrA
13	Blood culture	pyrG	16S rRNA
13	Skin culture	pyrG
14	Blood culture	fla	16S rRNA	fla
14	Vaginal culture	fla	16S rRNA	fla
15	Whole callus		16S rRNA
16	Whole callus		rpoC	rpoC
17	Whole callus	pyrG, uvrA	16S rRNA	pyrG, uvrA
17	Blood culture	Real-time 16S rRNA +/- equivocal
18	Whole callus	fla	16S rRNA	fla
21	Skin culture		16S rRNA +/- equivocal
23	Whole callus		16S rRNA	rpoC*
24	Blood culture	fla	16S rRNA
24	Vaginal culture		16S rRNA	rpoC**

*Sequence consistent with B. miyamotoi.
**Sequence consistent with B. garinii.
Amplicon sequences from all patients were consistent with Bb sensu stricto except for sequence from patient 23, which was consistent with B. miyamotoi, and patient 24, which was consistent with B. garinii.

Table 5. Detection of Bb DNA by *in situ* hybridization with Bb-specific DNA probes in samples derived from Morgellons patients
Patient #	Specimen	Probe FlaB	Probe 740
1	Callus	Not performed	Positive
2	Callus	Positive	Positive
3	Callus	Positive	Positive
4	Callus	Not performed	Positive
6	Skin culture	Not performed	Positive
7	Blood culture	Not performed	Positive
8	Callus	Not performed	Positive
10	Callus	Positive	Positive
11	Callus	Positive	Positive
12	Callus	Not performed	Positive
13	Callus	Positive	Positive
15	Callus	Positive	Positive
16	Callus	Not performed	Positive
18	Callus	Not performed	Positive
19	Callus	Positive	Positive
20	Callus	Positive	Positive
21	Skin culture	Positive	Not performed
21	Vaginal culture	Positive	Not performed
22	Callus	Positive	Not performed
24	Biopsy	Positive	Not performed