Open Access

Case report

Morgellons disease, illuminating an undefined illness: a case series

William T Harvey1*, Robert C Bransfield2, Dana E Mercer3, Andrew J Wright4, Rebecca M Ricchi5 and Mary M Leitao6
Addresses: 1Preventive Medicine, Colorado Springs, CO 80949, USA, 2Psychiatry, Red Bank, NJ, 07701, USA, 3Veterinary Medicine, Fulton, TX, 78358, USA, 4General Practitioner, Bolton BL1 4QR, UK, 5Adult Medicine, USAFA, CO, 80840, USA and 6BS (Biology), Guilderland, NY 12084, USA Email: WTH* - [email protected]; RCB - [email protected]; DEM - [email protected]; AJW - [email protected]; RMR - [email protected]; MML - [email protected] * Corresponding author

Received: 28 November 2008 Accepted: 17 March 2009 Published: 1 July 2009 Journal of Medical Case Reports 2009, 3:8243 doi: 10.4076/1752-1947-3-8243 This article is available from: http://jmedicalcasereports.com/jmedicalcasereports/article/view/8243 2009 Harvey et al; licensee Cases Network Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
Introduction: This review of 25 consecutive patients with Morgellons disease (MD) was undertaken for two primary and extremely fundamental reasons. For semantic accuracy, there is only one proven MD patient: the child first given that label. The remainder of inclusive individuals adopted the label based on related descriptions from 1544 through 1884, an internet description quoted from Sir Thomas Browne (1674), or was given the label by practitioners using similar sources. Until now, there has been no formal characterization of MD from detailed examination of all body systems. Our second purpose was to differentiate MD from Delusions of Parasitosis (DP), another informal label that fit most of our MD patients. How we defined and how we treated these patients depended literally on factual data that would determine outcome. How they were labeled in one sense was irrelevant, except for the confusing conflict rampant in the medical community, possibly significantly skewing treatment outcomes. Case presentation: Clinical information was collected from 25 of 30 consecutive self-defined patients with Morgellons disease consisting of laboratory data, medical history and physical examination findings. Abnormalities were quantified and grouped by system, then compared and summarized, but the numbers were too small for more complex mathematical analysis. The quantification of physical and laboratory abnormalities allowed at least the creation of a practical clinical boundary, separating probable Morgellons from non-Morgellons patients. All the 25 patients studied meet the most commonly used DP definitions. Conclusions: These data suggest Morgellons disease can be characterized as a physical human illness with an often-related delusional component in adults. All medical histories support that behavioral aberrancies onset only after physical symptoms. The identified abnormalities include both immune deficiency and chronic inflammatory markers that correlate strongly with immune cytokine excess. The review of 251 current NLM DP references leads us to the possibility that Morgellons disease and DP are grossly truncated labels of the same illness but with the reversal of the cause-effect order. Further, the patients data suggest that both illnesses have an infectious origin.

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Introduction
The term Morgellons disease first publicly appeared on the Internet in 2002. The index case was the first modern case to which that label was appended: a sick child whose physical signs and symptoms were collectively unrecognized as an entity at local and regional medical facilities. As the childs illness persisted without recognition or resolution, the unaffected parent sought similar illness descriptions from historic medical references, eventually settling on The Morgellons, a label given to childhood cases described in France in 1674 by Sir Thomas Browne [1]. His description was limited to its dermal components: hair-like extrusions and sensations of movement. Ettmuller, a physician, produced the only known drawings of The Morgellons in 1682 and considered these dermal filaments a parasitic infestation [1]. Numerous isolated descriptions of similar phenomena were found by Kellett from 1544 through 1884 that began as a pediatric-only illness identified by posterior torso bristles but also included extreme agitation, seizures, wasting and death (characteristics not seen in the 21st century). By the early 1600s, the illness was thought to be caused by the parasite Dracunculus (later called Dracontia, then pilaris affectio) and cured by filament (agent) removal from the skin. The worm theory was considered debunked by 1715 when the esteemed microscopist, Leuvenhoeck, pronounced the bristles inanimate. From this point forward to 1884, however, the illness shifted toward comedones, facial regions and to adults. And Demodex folliculorum was considered a frequent occupant of comedones, again supporting a parasite concept. The name Morgellons disease was thus created in 2002, as a practical place holder because of its dermal similarity to The Morgellons described by Browne in particular (Brownes The Morgellons label evolved further over three centuries into the words, Masquelon, then Masclous dicti and Les Crinons, shifting to Comedones after 1800). The new label also provided an alternative to differentiate a clearly, non-delusional child from many decades of clinical use of the label Delusions of Parasitosis [2-10]. This first set of actions would eventually raise one of the major philosophical questions of modern medicine: Does the practice of evidence-based medicine come from peer-reviewed literature, or from the actual patient? Information from what was later to become the Morgellons Research Foundation (MRF) website initially provided a broader look at the believed Morgellons disease symptoms by allowing patient registrants to record their symptoms and signs. Clearly, most of the 21st century patients did not fit the descriptions from 1500-1800. The MRF website provided a glimpse of the current global prevalence of those considering they are affected by this phenomenon. On January 2009, there are 13,000+ family registrants from all U.S. states and from 15 other countries. [http://www.morgellons.com/]

Given the growing use of the label Morgellons disease, characterizing the illness using verifiable clinical data seemed to be the imperative first step for clinicians, particularly to separate these patients from those two to five centuries before presentation. Until 2007, Morgellons and DP cases were often seen in isolation, interfering with credible Case Definitions. Assembling even this small number of candidate patients into a series with verified data points, should at least improved diagnosis consistency.
Case Series Data Collection The study protocol was simply a collection of clinical data obtained from new Morgellons disease patients at one clinic in a two-hour session between September 2006 and July 2007. Patients were not solicited but came self-diagnosed. Practice size limited the original patient number to 30 adults. The final number was 25 after filtering for consistency and data errors. Each clinical session included a detailed history, review of systems and a physical examination emphasizing dermal, neurological, endocrine and psychiatric systems. Expanded laboratory tests included a blood count (CBC), a metabolic panel (CMP) and others to evaluate major organ system function to characterize immune status, detect inflammation and search for an initial and limited number of possible infectious pathogens suggested by several veterinarians [personal communication].

Subjective screening criteria derived from earlier clinical encounters were first applied to improve patient selection consistency (Table 1). The screened data were then entered into 492 fields on each patient, 407 fields of which contained useful data points. This provided 10,175 total parameters for analysis.
Case Series Initial Data Summary The first-level summary of raw data is in the Appendix, Tables A, B and C. Categories devoid of entries had no significant findings.

Table 1. Initial Patient Screening Criteria 1. Patient convinced of chronic parasite infestation. 2. Primary patient illness focus must be either on dermal sensations or on never-before-seen material thought to be extruded from his or her body, even if this was not the most debilitating symptom or sign. The material must have been described as fibers, fiber-like, or filaments. 3. Chronic pruritis (itching) must have been present for at least six months. 4. The patient must have at least two chronic, unhealed skin lesions recorded by a clinician, regardless of whether excoriation was suspected. 5. Prior diagnosis of Delusions of Parasitosis or bipolar illness would not exclude the patient as a candidate. 6. Patients experiencing delusional states common in withdrawal from drugs such as opiates and patients in organic brain states, were excluded. 7. The illness must have had a life-altering effect on the patient. 8. The patient must be an adult and had experiencing symptoms for more than six months. 9. A healthy pre-morbid period in the patients life was acceptable.

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A. Demographic Information Male and female rates were the same for those who believed they had Morgellons disease. Age spread, geographic spread and gender neutrality were large. These data suggest Caucasian bias that did not appear in data from other countries [11]. B. Illness History Rural residence or recent rural travel was common. Emotional stress was not relevant, nor was season of onset. Physical stress was a common precursor. Full onset typically required one to several months from first symptom. C. Past Medical History Prior psychiatric diagnoses in more than half. The most common diagnosis was bi-polar illness. D. Social History Significantly reduced exercise capacity was highly prevalent although non-specific as an illness marker. Recent exposure to unhygienic settings (Third world countries, sewage systems and land fills) correlated strongly with illness onset. E. Systems Information from physical examination and History of Present Illness General: Weight gain after illness onset averaged to 33 pounds. High levels of fatigue and reduced exercise capacity were eventually present in 80% of patients. Recurrent fever by thermometry was noted by 50% of patients.

Cardiovascular: Patients often reported orthostatic intolerance and frequent arrhythmias (type undetermined) regardless of age. Rhythm and mild cardiac auscultation abnormalities (valvular) were commonly found on vital sign determination. Pulse was high (>72) in virtually all. Psychiatric: Strikingly, most patients in this study (23 out of 25) had prior psychiatric diagnoses (most determined by specialists) as follows: 11 out of 25 bipolar disease; 7 out of 25 Adult ADD; 4 out of 25 Obsessive Compulsive Disorder (OCD); and 1 out of 25 Schizophrenia. Although overlap occurred in 5 cases, only the primary psychiatric diagnosis was tabulated [14]. In each case, medical records indicated that the dermal symptoms and signs preceded or occurred simultaneously with the onset of emotional signs, with an emotionally normal time in each patients life prior to Morgellons disease. Endocrine: Eight patients (32%) had prior diagnoses of Hashimotos Thyroiditis. [The U.S. adult prevalence rate of Hashimotos Thyroiditis is 0.56%. The rate is based on 1996 statistics: 1,490,371 adults with Hashimotos Thyroiditis per U.S. population of 264,162,000. (Reference: Rose and Mackay, 1998, The Autoimmune Diseases, Third Edition)] Half had past evidence of Hypercalcemia (intermittent), of which 3 had definite parathyroid adenomas, later surgically excised with incomplete improvement. Fasting insulin levels were elevated in 100% who were tested for it (6 out of 25), as were CRH levels (also 6 out of 25 tested). Other: Recurrent cough and dyspnea were common as GI and urinary symptoms, but none had a recent medically determined etiology.
F. Vital Signs The most Consistent markers in this group were low core temperature and high resting heart rate, affecting all 25 patients. G. Laboratory Data CBC aberrancies were common but often intermittent. They included abnormal variable RBC indices, occasional low-grade anemia, low white cell count, and high monocyte count. Other abnormalities included low Natural Killer cell (CD56 + CD16) number and percentage, high or high-normal insulin level (in all tested) and intermittent elevation of serum calcium, globulin level, and A/G ratio. Sedimentation rate was mid-range normal or lower with only one ANA positive. Antidouble stranded DNA antibody level was negative in all tested. Occasionally IgG subclasses 1 and 3 were low. Commonly elevated markers supporting chronic inflammation included C-reactive protein and TNF-alpha. Other occasionally abnormal laboratory parameters present in
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Dermatological: A typical phrase used by most patients was similar to: Extruding and moving skin parasites (filaments, fibers, spheres) generating uncomfortable lesions. Patients stated filament appearance was intermittent and consistent with identifying in less than one in three patients on examination. The sensation of movement, however, was denied by up to 50% of those experiencing filament extrusions. About 70% had regular appearance of painful shallow skin ulcers, but most could easily separate excoriations (scratching) they had generated from spontaneous ulcers. Numerous micro-angiomas (0.5 to 3.0 mm in diameter) were found by examination on 72% of patients. This phenomenon is a known hallmark of Bartonellosis, although our patients had completely negative Bartonella serology [12,13]. Many patients noted that angiomata appearance directly paralleled illness onset and progression. Central Nervous System: This group experienced a high rate of headaches, visual aberrancies, tinnitus, and shortterm memory deficits. Emotional lability was present in more than half, typically manifest intermittently.

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chronic inflammation or infection included IFN-gamma, Homocysteine and serum Leptin. Most patients showed serologic evidence of infection (antibodies) with one or more unexpected potentially pathogenic microorganisms despite testing for only a few species.

were also elevated. There was a high prevalence of transient autoimmune diseases such as Hashimotos Thyroiditis, hyperparathyroidism and adrenal-cortical hypofunction. Following is a second level summary of the Morgellons data (Table 2). This is intended as a simplistic tool for clinical use.

Data Summary Following is the concluding summary of collected data from all patients, including pathological mechanisms suggested by the pattern(s) of these data anomalies.

Conclusion
Proposed Characterization of Morgellons Disease The authors conclude that Morgellons disease is a multisystemic illness that has been presumed as a delusional phenomenon for decades as its most obvious and disconcerting manifestations resembled actual (but unverified) parasite infestation as well as various psychopathologies. However, using recent technology and even a modicum of consistently obtained physical data supports that Morgellons manifest as a skin phenomenon, an immune deficiency state and a chronic inflammatory process. Since infectious agents can initiate and maintain chronic diseases, the behavioral and other CNS manifestations here are more likely effect than cause [18]. We suggest that the Morgellons label be considered to displace any label suggesting delusion as the primary cause of this phenomenon.

Morgellons disease was often preceded by exposure to unhygienic conditions and appears first as skin abnormalities and discomfort. Illness onset appears with moderately rapid transition (weeks) from healthy to unhealthy, including emotional discomfort. These gravid Morgellons females had an extraordinarily high miscarriage rate. The most common physical abnormalities found in this series include: 1) Numerous senile angiomas on the trunk, head and limbs of many; 2) Recurrent fever; 3) Awareness of itching, crawling, stinging or biting. When present, patients describe a circadian tempo to the symptoms; some occurring solely at night. Itching of unbroken skin specifically appeared to precede all other skin symptoms; 4) Unidentified objects (called filaments or granules) extrude uncomfortably from unbroken skin or skin lesions; 5) Painful ulcer-like concave, circular skin lesions with distinct border; 6) Excoriations adjacentto but separate from ulcerations were common; 7) Dermal symptoms were the central focus of discomfort for most patients. 8. Multiple organ system symptoms often appeared within the first six months of illness onset. The most common systems affected were the central and peripheral nervous systems, autonomic nervous system then endocrine, cardiovascular, and pulmonary systems. All blood pressures were low and all resting pulses were high. Routine laboratory tests were often inconsistent and varied both positively and negatively, but within range more frequently than out of range. Common abnormalities were NK cell numbers and percentages (low), and fasting insulin levels (very high). Occasionally abnormal were RBC indices, hematocrit, WBC count (low), monocyte count (high), serum calcium (high), globulin level (high), and A/G ratio (high). Contradictory autoimmunity data was frequently noted. Some expected inflammation tests such as sedimentation rate and Anti-double stranded DNA antibody tests were negative, while C-reactive protein and TNF-alpha were routinely high. IFN-gamma, Homocysteine and Leptin

The term Morgellons disease came into being in the 21st century in an attempt to identify an illness for which no name existed. The entry of this new label into a phenomenon of extreme controversy may at first appear to further that controversy. Typical of the evolution of medical nomenclature, however, the problem may always have been with semantics; in particular the use of assumptions unsupported from failure to investigate the total physical patient [19]. The index case that failed to fit similar earlier diagnostic labels was seen as different principally because its observer looked beyond the presumed signs and symptoms of the truncated look-alike phenomenon labeled Delusions of Parasitosis. Traberts review of 1,300+ cases makes clear that only a fraction of the total signs of that presumed illness were used to create the DP diagnostic framework [14,20]. Our attempt to gather as much physical evidence on Morgellons patients as possible was based on the extremely large number of abnormal physical signs among those we evaluated earlier. We gathered as many clinical parameters as possible (within the fiscal constraints of todays medicine) in order to see whether the abnormalities among them were consistent and if so, whether their pattern was explanatory. The unfolding mechanism strongly suggests a chronic infectious process.
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Table 2. Primary Abnormal Findings 1. The large age spread, geographic spread and gender neutrality among patients suggest broad human susceptibility to the illness. 2. Rural abode or exposure to unhygienic conditions (third world travel or simply soil exposure) may be risk factors. 3. Onset rate is moderately rapid, without recognizable prodrome, commonly preceded by a healthy state. 4. Once ill, exercise capacity is significantly reduced. 5. The illness is common among family members and close associates, both related genetically and unrelated (such as spouses). 6. Most patients experience weight gain after disease onset. 7. Micro-angiomas appear rapidly on skin after illness onset in most. 8. Fever is recurrent in at least half of those affected. 9. The first illness sign may be the sudden appearance of persistent itching. Ulcerative lesions follow in some cases. 10. Once dermal symptoms begin, patients experience extrusion of unfamiliar material described variously as filamentous, fuzz balls, black or white flecks or rice grains. 11. Numerous CNS effects occur, that includes bizarre cranial nerve phenomena, anxiety and emotional sequelae. The former tend to be transient. 12. Numerous Peripheral Nervous System findings appear after illness onset. Unlike CNS effects, these are serious, permanent and progressive, and include sensory and motor nerves. 13. All Morgellons have elevated heart rate (>72 BPM) and low body temperature by oral thermometry (<97.5 degrees F). 14. Orthostatic intolerance is intermittent but common in most. 15. Most have some formally diagnosable emotional illness that begins with or becomes apparent after Morgellons disease onset. 16. Endocrine abnormality number and type is higher than background. Most common are Diabetes Type II, Hashimotos Thyroiditis, hyperparathyroidism and adrenal hypofunction. 17. Most have elevated fasting insulin levels accompanied by elevated TNF-alpha (insulin receptor blocker) [15,16]. 18. Common clinical laboratory abnormalities include: a. RBCs have abnormal morphology. On manual examination, RBCs were non-discoid, varied in color and size. b. Natural Killer Cell (CD 56 + CD 16) number and function are very low in most. c. A/G ratio and globulin level are frequently elevated. d. Sedimentation Rate and ANA are extremely low despite other common autoimmune-like conditions. e. Elevated cytokines include: TNF-alpha, IFN-gamma, IL-6, C Reactive Protein, Homocysteine and serum Leptin. 19. Despite no fact-based Case Definition of Delusions of Parasitosis (DP), each of our 25 patients could have been given such an illness label as well. As pointed out by Trabert in a meta-analysis of 1,223 DP cases and others, most DP data were taken from isolated cases. Psychiatric-skewed labels were common such as psychocutaneous disease, acarophobia and monosymptomatic hypochondriasis with no serious search for consistent physical abnormalities or microscopic parasitic agents [17].

The specific agent candidates will not be addressed further until evidence of their presence is available and their presence can explain the signs and symptoms we now find in all Morgellons patients. There remains considerable work to do in collecting more data from these patients to create a credible Morgellons disease Case Definition. We submit that the same holds true for Delusions of Parasitosis patients [3]. Much of that work may be now under way by the U.S. Centers for Disease Control and Prevention (CDC) through contract with Kaiser Permanentes Northern California Division of Research. [http://www.cdc.gov/unexplaineddermopathy/] Meanwhile, the consistent abnormal findings in the data above may be used to improve clinical diagnosis and possibly initial treatment in current patients. Perhaps of considerable importance to a journal dedicated to Case Reports is what the juxtaposition of Morgellons disease and Delusions of Parasitosis suggests. As noted by Trabert in his meta-analysis, creating a Case definition primarily from isolated cases allows uncontrolled use of assumptions that vary considerably in order to keep an unresolved conclusion constant. Where many cases are used, consistency of similar data forces a far more valid and consistent conclusion [14,20]. Until the machinery of science is in full gear and provides understanding of this phenomenon, simply paying

attention, maintaining skepticism, practicing a simple physical exam and using commercial laboratories judiciously must suffice. Once the breadth and severity of what we are encountering is understood, the resources and motivation for its solution should come. When sufficient, we anticipate the framework of several medical specialties may be modified.

Consent
Written informed consent statements were obtained from the patients for publication of this case report. The copies of the written consent are available for review by the Editor-in-Chief of this journal.

Competing interests
The authors declare that they do not have any competing interests.

Authors contributions
WH crafted the submission in its final form, including the cover letter, abstract, title page and references, drafted the summary and conclusions, and submitted the package to JMCR. RB assisted with the completion of the entire submission and was responsible for all sections addressing psychiatric elements of the illness, particularly references to Delusions of Parasitosis. More will follow in paper #2. DM was responsible for all references to known parasite species and all conclusion statements considering parasitosis. AW analyzed all micrographs from several fluid and tissue
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sources for pathogen identification and contributed data from his own pool of anonymous UK patients for context. RR obtained medical histories and systems review from all series patients and applied her FBI forensics scrutiny training to complete a second physical examination on each patient. ML is the creator of the current Morgellons label and concept, and until characterized systematically, its sole authority. She created the Morgellons registration website, and modified this submission for consistency with the 1300+ site registrants. All authors read and approved the final manuscript.

9. 10. 11. 12. 13. 14. 15.

Acknowledgements
None.
16.

References
1. 2. 3. 4. 5. 6. Kellett C: Sir Thomas Browne and the Disease called the Morgellons. Annals of Medical History 1935, 7:467-479. Robles DT et al.: Delusional disorders in dermatology: a brief review. Dermatol Online J 2008, 14:2. Berrios GE: Delusional parasitosis and physical disease. Compr Psychiatry 1985, 26:395-403. Szepietowski JC et al.: Delusional parasitosis in dermatological practice. J Eur Acad Dermatol Venereol 2007, 21:462-465. Nicolato R et al.: Delusional parasitosis or Ekbom syndrome: a case series. Gen Hosp Psychiatry 2006, 28:85-87. Aw DC, Thong JY, Chan HL: Delusional parasitosis: case series of 8 patients and review of the literature. Ann Acad Med Singapore 2004, 33:89-94. Koo J, Gambla C: Delusions of parasitosis and other forms of monosymptomatic hypochondriacal psychosis. General discussion and case illustrations. Dermatol Clin 1996, 14:429-438. Johnson GC, Anton RF: Delusions of parasitosis: differential diagnosis and treatment. South Med J 1985, 78:914-918. 17. 18. 19. 20.

Amato Neto et al.: Ekbom syndrome (delusory parasitosis): ponderations on two cases. Rev Inst Med Trop Sao Paulo 2007, 49:395-396. Bouree P, Benattar B, Perivier S: Ekbom syndrome or delusional parasitosis. Rev Prat 2007, 57:585-589. Savely VR, Leitao MM, Stricker RB: The mystery of Morgellons disease: infection or delusion? Am J Clin Dermatol 2006, 7:1-5. Podsiadly E, Chmielewski T, Tylewska-Wierzbanowska S: Bartonella henselae and Borrelia burgdorferi infections of the central nervous system. Ann N Y Acad Sci 2003, 990:404-406. Brouqui P et al.: Ectoparasitism and vector-borne diseases in 930 homeless people from Marseilles. Medicine (Baltimore) 2005, 84:61-68. Aaron LA, Buchwald D: A review of the evidence for overlap among unexplained clinical conditions. Ann Intern Med 2001, 134:868-881. Holden RJ, Pakula IS, Mooney PA: Tumor necrosis factor-alpha: a continuum of liability between insulin-dependent diabetes mellitus, non-insulin-dependent diabetes mellitus and carcinoma (review). Med Hypotheses 1999, 52:319-323. Nishimura M et al.: Role of tumor necrosis factor-alpha in insulin sensitivity and effect of low protein diet on the TNFalpha response in patients with diabetic renal failure. Nippon Jinzo Gakkai Shi 1997, 39:740-745. Trabert W: Epidemiology of delusional ectoparasitic infestation. Nervenarzt 1991, 62:165-169. Ewald PW: The evolution of virulence. Sci Am 1993, 268:86-93. Ruchlis H: Clear Thinking: a practical introduction. 1st edition. 1990, Buffalo, NY: Promethius Books, 1990:271. Trabert W: 100 years of delusional parasitosis. Meta-analysis of 1,223 case reports. Psychopathology 1995, 28:238-246.

APPENDIX
TABLES OF RESULTS NOTE: These tables are a first level summary of the complete basic data set except for physical examination findings that are summarized above. Although subjectivity has been introduced, we have attempted to keep it separate as footnotes.

7.

8.

Table A. Basic Background Data Demographics Countries of origin: U.S., U.K., Canada, Japan Male: Female ratio approximates 50:50 Age range: 10-75 years 24/25 were Caucasian1 Urban: Rural ratio = 50:502 Past medical history 11out of 25 were diagnosed with bipolar disease 7 out of 25 were diagnosed with adult ADD 1 out of 25 was diagnosed with schizophrenia Common childhood illnesses were absent regardless of vaccination status 19 out of 25 had been given general anesthesia at least once* 9 out of 25 had prior orthopedic surgery* 6 out of 25 had other prior surgery for chronic inflammatory diseases (appendix, gallbladder)* 50% were married/ 50% single* 28% were smokers* None routinely exercised*

Illness History

Time from initiation to full onset: several months Social History Exposure to unhygienic conditions occurred several days to several weeks prior to illness onset Patients claimed relative healthiness prior to Morgellons (as initially described) onset; No consistent recognized prodrome heralded onset of the illness Allergy symptoms were rare Activating stressor event was present in 1 out of 3 of cases.

Highest relevancy results. Findings that may help to isolate, identify, and define Morgellons disease. * Other data. 1 This sample was not adequate to determine whether race is a factor. The high percentage of Caucasian patients was likely related to clinic location. Earlier and subsequent data of larger numbers from more heterogeneous regions suggest that race is likely not a risk factor. 2 The urban to rural ratio may be significant. Although only 20% of people live in rural areas, 50% of the patient samples were in rural regions near the onset of their illness, lending support to the hypothesis that exposure to unhygienic conditions or animals may be a risk factor.

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Table B. Review of Systems Dermatologic 24% of patients had dark filaments visibly protruding from the skin1 17 out of 25 had frequent skin eruptions/rashes Just over 50% experienced no movement sensations Only 50% itched regularly 72% has angiomata appear Average weight gain after onset: 33 lbs 2 20 out of 25 experienced regular high levels of fatigue Central Nervous System Over half had frequent headaches Over half had unstable visual acuity including double vision (10 out of 25) 10 out of 25 reported visual flashes (not characterized) in either daylight or dark Emotional liability in half of patients 1/3 reported frequent dizziness 1/3 reported permanent hearing loss (degree not determined) 40% reported tinnitus 20 out of 25 reported frequent occurrence of forgetfulness 12 out of 25 had persistent regional skin numbness 6 out of 25 had persistent tremors 25% were intolerant to cold and 25% intolerant to heat (some overlap, but degree undetermined) 10 out of 25 reported sweating inappropriately (either under- or over-sweating) 8 out of 25 had prior diagnosis of Hashimotos Thyroiditis 50% had hypercalcemia, 3 of whom had parathyroid adenomas Fasting insulin levels were elevated in all tested (6 out of 25) Corticotrophin Releasing Hormone (CRH) levels were elevated in all tested

Metabolic

Immune

12 out of 25 had cyclical fever 18 out of 25 reported numerous angiomas verified by examination 10 out of 25 reported many colds annually* 8 out of 25 reported chronic sinusitis* 4 out of 25 reported frequent sore throats over a period of years* 2 out of 25 reported frequent toothaches*

Endocrine

Musculo-skeletal 15 out of 25 reported frequent neck pain 10 out of 25 had persistent limited neck movement 22 out of 25 had chronic musculoskeletal pain, without arthritis Pain was constant and incapacitating in 1/3 of patients Emotional Half reported anxiety Half reported frequent mood swings Half reported frequent depression

Gastro-intestinal

50% had constipation or diarrhea, or both (overlap was common) 25% had chronic nausea Persistent cough (non-productive, non-wheezing) in 9 out of 25 Persistent dyspnea in 7 out of 25 Urine stream control problems in 6 out of 25

Pulmonary

Other

1 2

Less than half of the 25 patients studied reported the presence of filaments, and as a result, the authors did not search for filaments on all patients. Average weight gain in male and female patients combined. Time period for weight gain undetermined.

Table C. Vital Signs and Laboratory Data Lab Parameters Vital Signs Laboratory Data WBC RBC HGB Unidentified lymphatic filamentous clusters were found in 4 patients ABNL INDICES 50% were positive for Borrelia burgdorferi sensu lato either by CDC Western % SEGS % MONOS Blot (WB) criteria, EUCALB WB (IgM P31 and 34 added), or IFA1 4 patients were seropositive for Babesia microti2 % EOS 92% were seropositive for Chlamydia pneumonia (Chp)3 NK# (CD56/57) NK% (CD56/57) GLU (RANDOM) BUN CREAT SODIUM CHLORIDE CO2 CALCIUM T. PROT ALBUMIN GLOBULIN A/G RATIO Average temp 97.51 F Average pulse 85.32 BPM Laboratory Values4 6.76 (2.9-10.5) 4.89 (3.90-5.70) 16.36 (11.6-17.0) 28%5 58.26 6.898 1.85 71.859 11.2 97.95 (Random range 73-99) 10 13.57 (9-26) 0.86 (0.3-0.9)11 141.65 (137-146) 105.09 (96-111) 26.09 (22-31)12 9.65 (8.8-10.3)13 7.32 (6.2-8.2) 4.68 (3.7-5.0)14 3.7 (2.2-3.5)15 2.63 (1.2-2.0)16 (Continued)

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Table 4. (Continued)
Lab Parameters ALK PHOS AST ALT SED RATE ANA (POSITIVE) ADSDNA-AB (POSITIVE) ONE LOW IgG SUBCLASS TSH ATA POS IL-1A HIV POS CRP IL-1B IL-6 TNF-a TGF-b 108 LEPTIN
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Laboratory Values4 97.74 28.73 30.95 11.39 1 0 4 2.14 (0.4-4.5)19 0 51.2 (25-150) 1 3.44 (< 0.81 mg/dL)20 113.83 (< 150)21 3.48 (0-3.6)22 16.92 (0-8.1)23 (0 -100 pg/dL)24 13.66 (0.7-5.3 M)25 (40-99) 17 (17-49) (12-46) (0-20)18

Suggests Borrelia may contribute to some cases of Morgellons disease. Suggests Babesia is uncommon in most Morgellons disease cases. 3 Suggests Chlamydia pneumonia (Chp) is one candidate for the initial etiology of Morgellons disease via generation of an immunodeficiency state. 4 Lab tests were drawn at 6,100 feet MSL (above mean sea level). 5 RBC characteristics were adjusted for elevation. All indices should be normal. 6 Lower than regional mean of 66%. 7 Slightly higher than regional mean of 28%. 8 Much higher than regional mean of 3.0%. 9 Although a broad normal range exists for NK number, our clinical experience supports that consistently healthy individuals who rarely experience viral syndromes have NK # > 200. Our patients range is not infrequently below 10. This suggests one component of an immune deficiency state. 10 Well above regional mean of 84. 11 Well above regional mean of 0.6. 12 Although clearly within range at 6,100 ft. MSL, the mean of more than 100 similar patients tested near sea level (2001-2004) was 18 (21-28 anticipated). As low CO2 level translates to low serum bicarbonate level, this suggests required buffering to lower acidity. Although there are several causes of elevated serum acidity, many of these patients underwent overnight studies for sleep apnea that revealed consistent low breathing rate raising PCO2. No such formal test was included in testing these patients although we believe such testing would be highly revealing. 13 Despite this average being satisfactory, 7 of the 25 patients tested were between 10.0 and 10.6. Three of 25 patients were found to have parathyroid adenomas. 14 Greater than 5.0 in 9 of 25. 15 The converse of immune deficiency, however, suggests that a possible chronic infectious state may have been operant that could intermittently activate humoral immunity. 16 Commonly above 2.0. As globulin is elevated and albumin is clearly not low, the ratio elevation is driven somehow by the albumin. This is presently a paradox. 17 Average is high normal and well above the regional mean of 68. Suggests skeletal involvement in the disease, although liver involvement is possible. Most Morgellons patients have shown evidence of osteopenia or osteoporosis when randomly tested despite age. Bone density was not determined in these 25 patients. We believe doing so would be valuable. 18 Argues against an autoimmune role, particularly as 5 out of 25 were 0, and all were less than 20. 19 Despite this normal finding, Hashimotos Thyroiditis is common in larger similar groups of Morgellons. Further evaluation of the HP axis and the endocrine system in general should be included in any future studies. 20 Currently used to assess cardiac risk in three stages. In this context, we are assessing chronic inflammation. This average supports the presence of a persistent inflammatory process that parallels physical evidence of vasculitis. 21 Five >150, suggests cytokine activation and possible inflammatory effect. 22 High-normal. 11 out of 25 >3.6, suggests cytokine activation and possible inflammatory effect. 23 Definite elevation in 92%. Most commonly corresponds to insulin receptor blockade and to chronic inflammatory effects. 24 Elevation of Transforming Growth Factor beta (TGF-beta) can occur when pathological events diminish its protective growth modulating effects on various tissues. This test result parallels evidence of excessive growth processes observed in these patients such as numerous angiomata, skin tags, nevi, and regions of increased epidermis density. 25 Consistently elevated in most male and female study patients. Parallels the gain in body fat and angiogenesis experienced by most following illness onset.
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