Exploring the association between Morgellons disease and Lyme disease: identification of Borrelia burgdorferi in Morgellons disease patients

BMC Family Practice

Raphael B Stricker³  Peter J Mayne⁴  Agustin Franco¹  Yean Wang¹  Katherine R Filush²  Eva Sapi²  Jennie Burke¹  Cheryl Bandoski²  Marianne J Middelveen⁴ 

[1] Australian Biologics, Sydney, NSW, Australia;Department of Biology and Environmental Science, University of New Haven, West Haven, CT, USA;450 Sutter Street, Suite 1504, San Francisco 94108, CA, USA;International Lyme and Associated Diseases Society, Bethesda, MD, USA

关键词: Dermopathy;    Spirochetes;    Borrelia burgdorferi;    Lyme disease;    Morgellons disease;   

Others  :  1142374
DOI  :  10.1186/s12895-015-0023-0

 received in 2014-08-21, accepted in 2015-01-28,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Middelveen et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Savely VR, Leitao MM, Stricker RB: The mystery of Morgellons disease: Infection or delusion? Am J Clin Dermatol 2006, 7:1-5.
• [2]Savely G, Leitao MM: Skin lesions and crawling sensation: disease or delusion? Adv Nurse Pract 2005, 13:16-17.
• [3]Savely VR, Stricker RB: Morgellons disease: the mystery unfolds. Expert Rev Dermatol 2007, 2:585-591.
• [4]Savely VR, Stricker RB: Morgellons disease: analysis of a population with clinically confirmed microscopic subcutaneous fibers of unknown etiology. Clin Cosmet Investig Dermatol 2010, 3:67-78.
• [5]Middelveen MJ, Stricker RB: Filament formation associated with spirochetal infection: A comparative approach to Morgellons disease. Clin Cosmet Investig Dermatol 2011, 4:167-177.
• [6]Middelveen MJ, Mayne PJ, Kahn DG, Stricker RB: Characterization and evolution of dermal filaments from patients with Morgellons disease. Clin Cosmet Investig Dermatol 2013, 6:1-21.
• [7]Middelveen MJ, Burugu D, Poruri A, Burke J, Mayne PJ, Sapi E, et al.: Association of spirochetal infection with Morgellons disease. F1000 Res 2013, 2:25.
• [8]Mayne P, English JS, Kilbane EJ, Burke JM, Middelveen MJ, Stricker RB: Morgellons: a novel dermatological perspective as the multisystem infective disease borreliosis. F1000 Res 2013, 2:118.
• [9]Middelveen MJ, Rasmussen EH, Kahn DG, Stricker RB: Morgellons disease: A chemical and light microscopic study. J Clin Exp Dermatol Res 2012, 3:140.
• [10]Shah JS, Du Cruz I, Narciso W, Lo W, Harris NS: Improved sensitivity of Lyme disease Western blots prepared with a mixture of Borrelia burgdorferi strains 297 and B31. Chronic Dis Int 2014, 1:7.
• [11]Bankhead T, Chaconas G: The role of VlsE antigenic variation in the Lyme disease spirochete: persistence through a mechanism that differs from other pathogens. Mol Microbiol 2007, 65:1547-1558.
• [12]Middelveen MJ, McClain SA, Bandoski C, Israel JR, Burke J, MacDonald AB, et al.: Granulomatous hepatitis associated with chronic Borrelia burgdorferi infection: a case report. Research Open Access 2014, 1:875.
• [13]Sapi E, Kaur N, Anyanwu S, Luecke DF, Datar A, Patel S, et al.: Evaluation of in-vitro antibiotic susceptibility of different morphological forms of Borrelia burgdorferi. Infect Drug Resist 2011, 4:97-113.
• [14]O'Rourke M, Traweger A, Lusa L, Stupica D, Maraspin V, Barrett PN, et al.: Quantitative detection of Borrelia burgdorferi sensu lato in erythema migrans skin lesions using internally controlled duplex real time PCR. PLoS One 2013, 8:e63968.
• [15]Margos G, Hojgaard A, Lane RS, Cornet M, Fingerle V, Rudenko N, et al.: Multilocus sequence analysis of Borrelia bissettii strains from North America reveals a new Borrelia species. Borrelia kurtenbachii Ticks Tick Borne Dis 2010, 1:151-8.
• [16]Sapi E, Pabbati N, Datar A, Davies EM, Rattelle A, Kuo BA: Improved culture conditions for the growth and detection of Borrelia from human serum. Int J Med Sci 2013, 10:362-376.
• [17]Clark KL, Leydet B, Hartman S: Lyme borreliosis in human patients in Florida and Georgia. USA Int J Med Sci 2013, 10:915-931.
• [18]Mayne PJ: Investigations of Borrelia burgdorferi genotypes in Australia obtained from erythema migrans tissue. Clin Investig Dermatol Res 2012, 5:69-78.
• [19]Lorenzo CR, Koo J: Pimozide in dermatologic practice: A comprehensive review. Am J Clin Dermatol 2004, 5:339-349.
• [20]Freudenmann RW, Lepping P: Delusional infestation. Clin Microbiol Rev 2009, 22:690-732.
• [21]Hylwa SA, Bury JE, Davis MD, Pittelkow M, Bostwick JM: Delusional infestation, including delusions of parasitosis: Results of histologic examination of skin biopsy and patient-provided skin specimens. Arch Dermatol 2011, 147(9):1041-5.
• [22]Pearson ML, Selby JV, Katz KA, Cantrell V, Braden CR, Parise ME, et al.: Clinical, epidemiologic, histopathologic and molecular features of an unexplained dermopathy. PLoS One 2012, 7(1):e29908.
• [23]Stricker RB, Middelveen MJ: Morgellons disease: More questions than answers. Psychosomatics 2012, 53(5):504-505.
• [24]Cheli R, Mortellaro CM: Digital dermatitis in cattle. Proc 8th Int Meet Dis Cattle Milan. Italy 1974, 8:208-213.
• [25]Blowey RW, Sharp MW: Digital dermatitis in dairy cattle. Vet Rec 1988, 122:505-508.
• [26]Read DH, Walker RL, Castro AE, Sundberg JP, Thurmond JC, et al.: An invasive spirochaete associated with interdigital papillomatosis of dairy cattle. Vet Rec 1992, 130:59-60.
• [27]Borgmann JE, Bailey J, Clark EG: Spirochete-associated bovine digital dermatitis. Can Vet J 1996, 37:35-37.
• [28]Döpfer D, Koopmans A, Meijer FA, Szaskall I, Schukken WH, Klee W, et al.: Histological and bacteriological evaluation of digital dermatitis in cattle, with special reference to spirochaetes and Campylobacter faecalis. Vet Rec 1997, 140:620-3.
• [29]Read DH, Walker RL: Papillomatous digital dermatitis (footwarts) in California dairy cattle: clinical and gross pathologic findings. J Vet Diagn Invest 1998, 10:67-76.
• [30]Vink WD, Jones G, Johnson WO, Brown J, Demirkan I, Carter SD, et al.: Diagnostic assessment without cut-offs: application of serology for the modeling of bovine digital dermatitis infection. Prev Vet Med 2009, 92:235-48.
• [31]Grund S, Nattermann H, Horsch F: Electron microscopic detection of spirochetes in digital dermatitis of cattle. Zentralbl Veterinarmed B 1995, 42:533-542.
• [32]Demirkan I, Carter SD, Murray RD, Blowey RW, Woodward MJ: The frequent detection of a treponeme in bovine digital dermatitis by immunohistochemistry and polymerase chain reaction. Vet Microbiol 1998, 60:285-92.
• [33]Berry SL, Read DH, Famula TR, Mongini A, Döpfer D: Long-term observations on the dynamics of bovine digital dermatitis lesions on a California dairy after topical treatment with lincomycin HCl. Vet J 2012, 193:654-658.
• [34]Döpfer D, Anklam K, Mikheil D, Ladell P: Growth curves and morphology of three Treponema subtypes isolated from digital dermatitis in cattle. Vet J 2012, 193:685-693.
• [35]Malane MS, Grant-Kels JM, Feder HM Jr, Luger SW: Diagnosis of Lyme disease based on dermatologic manifestations. Ann Intern Med 1991, 114:490-498.
• [36]Afa G, Caprilli F, Crescimbeni E, Morrone A, Progano G, Fazio M: Anti-Borrelia burgdorferi antibodies in chronic erythema migrans, benign lymphadenosis cutis, scleroderma and scleratrophic lichen. G Ital Dermatol Venereol 1990, 125:369-373.
• [37]Chao LL, Lu CF, Shih CM: Molecular detection and genetic identification of Borrelia garini and Borrelia afzelii from patients presenting a rare skin manifestation of prurigo pigmentosa in Taiwan. Int J Infect Dis 2013, 17:1141-1147.
• [38]Vasudevan B, Chatterjee M: Lyme borreliosis and skin. Indian J Dermatol 2013, 58:167-174.
• [39]Ekbom KA, Yorston G, Miesch M, Pleasance M, Rubbert S: The pre-senile delusion of infestation. 1945. Translation: Hist Psychiatry 2003, 14(54 Pt2):229-256.
• [40]Georgilis K, Peacock M, Klempner MS: Fibroblasts protect the Lyme disease spirochete, Borrelia burgdorferi, from ceftriaxone in vitro. J Infect Dis 1992, 166:440-444.
• [41]Klempner MS, Rogers RA, Noring R: Invasion of fibroblasts by the Lyme spirochete Borrelia burgdorferi. J Infect Dis 1993, 167:1074-1081.
• [42]Chmielewski T, Tylewska-Wierzbanowska S: Interactions between Borrelia burgdorferi and mouse fibroblasts. Pol J Microbiol 2010, 59:157-160.
• [43]Stricker RB, Johnson L: Serologic tests for Lyme disease: more smoke and mirrors. Clin Infect Dis 2008, 47:1111-1112.
• [44]Dattwyler RJ, Volkman DJ, Luft BJ, Halperin JJ, Thomas J, Golightly MG: Seronegative Lyme disease. N Engl J Med 1988, 319:1441-1446.
• [45]Schmidt BL: PCR in laboratory diagnosis of human Borrelia burgdorferi infections. Cin Microbiol Rev 1997, 10:185-201.
• [46]Lange R, Seyyedi S: Evidence of a Lyme borreliosis infection from the viewpoint of laboratory medicine. Int J Med Microbiol 2002, 291(Suppl 33):120-124.
• [47]Péter O, Bretz AG, Bee D: Occurrence of different genospecies of Borrelia burgdorferi sensu lato in ixodid ticks of Valais. Switzerland Eur J Epidemiol 1995, 11:463-467.
• [48]Mursic VP, Wanner G, Reinhardt S, Wilske B, Busch U, Marget W: Formation and cultivation of Borrelia burgdorferi spheroplast-L-form variants. Infection 1996, 4:218-226.
• [49]Brorson O, Brorson SH: An in vitro study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to tinidazole. Int Microbiol 2004, 7:139-142.
• [50]Embers ME, Barthold SW, Borda JT, Bowers L, Doyle L, Hodzic E, et al.: Persistence of Borrelia burgdorferi in rhesus macaques following antibiotic treatment of disseminated infection. PLoS One 2012, 7:e29914.
• [51]Meriläinen L, Herranen A, Schwarzbach A, Gilbert L. Morphological and biochemical features of Borrelia burgdorferi pleomorphic forms. Microbiology. published ahead of print January 6, 2015, doi:10.1099/mic.0.000027
• [52]Mayne PJ: Clinical determinants of Lyme borreliosis, babesiosis, bartonellosis, anaplasmosis, and ehrlichiosis in an Australian cohort. Int J Gen Med 2015, 8:15-26.
• [53]Alessi E, Innocenti M, Ragusa G: Secondary syphilis: Clinical morphology and histopathology. Am J Dermatopathol 1983, 5(1):11-17.
• [54]Zoechiling N, Schluepen EM, Soyer HP, Kerl H, Volkenandt M: Molecular detection of Treponema pallidum in secondary and tertiary syphilis. Br J Dermatol 1997, 136:683-6.
• [55]Pereira TM, Fernandes JC, Viera AP, Basto AS: Tertiary syphilis. Int J Dermatol 2007, 46:1192-5.