Wednesday, January 02, 2019

Studies of interest to anyone concerned about petechiae as a sign of Kaposi's sarcoma in Chronic Fatigue Syndrome.

Classic Kaposi’s Sarcoma Associated with Human Herpesvirus 8 Infection in a 13-Year-Old Male

http://clincancerres.aacrjournals.org/content/7/8/2263

Can most of the symptoms of Chronic Fatigue Syndrome described by Paul Cheney be attributed to internal Kaposi's Sarcoma?



Source:
http://cfstreatment.blogspot.com/2014/07/

This paper (below) by Dr. Paul Cheney and Dr. Charles Lapp was written more than two decades ago. It contains detailed descriptions of numerous test abnormalities found in ME/CFS patients, all which can be used for diagnosis.

____________________________

The Diagnosis of Chronic Fatigue Syndrome: An Assertive Approach by Paul R. Cheney, MD, PhD and W. Charles Lapp, MD, FAAP

Introduction: The Case for Diagnosis by Objective Criteria

Over the past ten years, a considerable and diverse medical literature has arisen concerning the chronic fatigue syndrome (CFS). Like all medical literature written on an emerging disorder, these published findings include a range of views and some discrepancies.

Systematic errors exist among the tools used to discern differences between CFS cases and "healthy" controls. The central problem, however, is case selection. Many patients with CFS are excluded from studies because they seem "too sick" to have CFS and are perceived as having something else. CFS cases are mixed in with non-cases. Inappropriate controls are sometimes used. Some investigators, aware or unaware of a bias, attract or include in their studies the very patients who best fit their view of CFS. This so-called selection bias can markedly affect the observations of a study. Despite these discrepancies, a more or less consistent pattern of observable abnormalities has emerged and we believe a case definition using objective abnormalities can now be defended.

Having stated the inherent problems with CFS research, we will attempt to defend an assertive approach (i.e.,diagnosis by inclusion) to the diagnosis of CFS using the available medical literature to support it. This is a different approach from just applying the Centers for Disease Control (CDC) case definition, which in essence defines a sign-symptom complex in the absence of a "known medical illness" (i.e., diagnosis by exclusion). The medical evidence cited for CFS asserts that the following are present more or less in every patient during the course of his or her disease: T-cell activation, discrete immune defects, viral activation or re-activation, exercise-related dysfunction, and evidence of brain dysfunction or injury. While none of these tests can stand alone to "diagnose" the illness, an array of these tests can be used to support this diagnosis, given the proper clinical context derived through the application of the CDC case definition. The use of non-specific tests to defend or support a diagnosis is a time-honored tradition in medicine, and the concept is used to diagnose such disorders as multiple sclerosis, lupus erythematosus, acute infectious mononucleosis, and even AIDS.

There are a number of criticisms given for using nonspecific tests in the diagnosis of CFS. They include the following:

(1) We lack a gold standard for determining this disorder and therefore lack a means to test the relative value of certain tests (i.e., false positive and false negative rates).

This is certainly a valid point in confirming a diagnostic test, but it is not a valid criticism in using a non-specific test to support a clinical impression. If a test abnormality has been shown in the medical literature to be associated with a certain disease, such as a positive ANA in lupus, then it is valid test to be used in supporting a clinical diagnosis. Furthermore, as in the "diagnostic" tests for the hepatitis C virus and the Lyme agent, poor test performance may be ignored in the case where benefits, however defined, outweigh poor performance.

(2) Even if there are test abnormalities which can be associated with CFS there is no need to make a more definitive diagnosis because there is no treatment for the disease.

If this were a valid argument, then it would also apply to multiple sclerosis, many cancers, acute infectious mononucleosis, and even AIDS. Documentation of an illness by objective criteria is important not only to confirm the diagnosis, but also to reassure the patient about other disorders they may or may not have. Reassurance is itself therapeutic and proportional to the degree of objective support found for a diagnosis.

Though there may be no scientifically validated treatment options for CFS (a situation which may soon change with the recent conclusion of the Ampligen trials), there are many therapeutic rationales based on test abnormalities which can defend empiric therapy. Such rationale exist for T-cell activation, certain immune deficiency states, herpes-group virus reactivation and even nonspecific brain injury. In the everyday practice of medicine, empiric therapy is often warranted in severe or functionally devastating illness. It is common practice to use unproven but rational therapies to treat clinical diagnoses such as a migraine, PAS, atypical depression, and many other disorders. Finally, documentation of abnormalities associated with CFS can assist the patient in disability arguments.

Disability Law Judges almost never respond favorably to disabling disorders without objective findings. This is even more the case for emerging disorders. The ability to successfully argue for disability is an extremely important aspect of therapy for this disorder. We have several examples of patients coming off disability and returning to work in part because the disability concept can itself be therapeutic.

(3) CFS is a "self-limited illness" which nearly always responds to rest, good nutrition, and proper exercise. As such, little is gained from extensive testing other than to disprove the presence of other disorders.
This misperception of CFS patients is pervasive among many clinicians and the lay public. A debilitating illness lasting years or longer is in fact not self-limited, and it deserves considerable medical attention. Some patients appear to be permanently disabled by this disorder. It may not completely or permanently resolve even in most patients who do see improvement over time. There are theoretical reasons to be concerned and vigilant about long-term health issues in all CFS patients.

Also, and intuitively, it seems to us to be helpful to intervene early in the course of CFS, even if only to dispel the false idea that any exercise will help this disorder and to counsel patients on lifestyle adjustment and symptom relief, especially for sleep disorder. Good documentation of this disorder lays the groundwork for future empiric intervention should it be necessary and gives a baseline with which to compare future results.

The CDC Case Definition

A case definition for CFS proposed by researchers at the CDC and elsewhere was published in 1988 1 . This clinical case definition consists of both major (all must be met) and minor (some but not all must be met) criteria. Difficulties in the application of this case definition include: How does one define a 50 percent or greater reduction in activity? Exactly how far does one go to exclude other disorders? What does one do with patients with remote onset--say in childhood—of chronic fatigue who would be excluded by the current case definition? Should some minor criteria be moved to major criteria and others dropped entirely? What does one do with patients who have confounding medical and psychiatric problems which might explain some if not all of their symptoms? What does one do with patients who lack severity criteria or sufficient signs and symptoms? What signs or symptoms and what other objective tests should be added to sharpen the diagnosis?

While some of these questions have been partially addressed by the authors of the CDC case definition, most persist and are handled differently by different investigators. Despite the problems with the present case definition, we believe that it generally functions to separate most cases from possible or probable non-cases. We recommend continued use of the criteria but designate probable non-cases who meet criteria and probable cases who do not meet criteria as atypical cases or non-cases of CFS.

Further subdivision of atypical cases by severity and confounding medical or psychiatric issues is probably a worthwhile endeavor and has been adopted by the CDC in their surveillance studies.

Clinical Observations Helpful in the Diagnosis of CFS

We have had the opportunity to make a number of clinical observations in over 1,200 cases of CFS which we believe are helpful in the diagnosis of CFS. None of these findings can be used individually to diagnose a case, but they add collective weight to the final clinical judgment. Some patients will have a normal physical examination and many will have essentially normal routine laboratory values.

Physical Findings - Contrary to suggestions by some investigators, abnormalities on physical examination, although sometimes subtle, are usually present:
  1. Fever at or above 99.2 F in 38% of patients
  2. Subnormal temperatures
  3. Intermittent tachycardia
  4. Low blood pressures
  5. Abnormal oral pharynx exam, including: buccal mucosal ulcerations; posterior cobblestoning, erythema and "crimson crescents" over soft palate; tongue coatings or blisters; and rare thrush
  6. Fluctuating anisocoria over time in dim light
  7. Photophobia
  8. End gaze nystagmus
  9. Posterior cervical lymphadenia with slight, palpable enlargement, usually asymmetric
  10. Axillary lymphadenia with slight, palpable enlargement, usually asymmetric
  11. Tender points typical for fibromyalgia
  12. Mild to severe skin atrophy of distal finger tips, loss of fingerprints
  13. Diffuse abdominal tenderness
  14. Hyperreflexia is very common, worse in lower extremities, and with occasional unsustained clonus
  15. Mild tremulousness on drift testing
  16. Intention tremor
  17. Mitral valve prolapse
  18. Sallow skin tone
  19. Brittle, thinning hair with reddish tint
  20. Excessive titubation or actual inability to maintain Romberg or tandem stance and tandem walk (probably represents an apraxia or vestibular disturbance and very common in these patients)
  21. Tentativeness or inability to serial seven subtract, especially while attempting Romberg test, is very common
  22. Facial and torso rashes, mostly macular erythema and acneform eruptions
Routine Laboratory Tests - Findings may be subtle but are often present
  1. Low sedimentation rates in 40% (0-3 mm/hr); modestly elevated (20-40) in 10%, usually will fall over time
  2. Akaline urines are common (PH>7.0)
  3. Mild leukocytosis or leukopenia
  4. Macrocytosis with elevated MCV
  5. Mild LFT elevations, rarely persist
  6. Atypical lymphocytes
  7. Elevated blood lipids
  8. Low normal free T4 and TSH
  9. Low level ANAs, may not persist
  10. Rare positive Lyme antibodies - failure to respond to accepted therapy
Immunologic Dysfunction

Immunologic tests have been frequently applied to patients with CFS in part because they are frequently abnormal and in part because the signs and symptoms of CFS can be explained as a consequence of immunologic function or dysfunction. Fever, sore throat, swollen glands, aching muscles and joints, sleep disturbance, and even neuropsychological complaints can all be attributed to immunologic responses generally ascribed to T-cell activation with excess cytokine production (i.e., IL-1 alpha, IL-2, interferon-alpha). Whether this excessive immune response is itself the cause (auto-immune or neuroendocrine defects) of CFS or perhaps the effect of a chronic viral infection or even compensation, by whatever means, for an acquired immune deficiency remains uncertain.

We propose here a set of tests that look for evidence of T-cell activation along with discrete immune defects.  All of these tests are available from commercial laboratories and defended by published medical literature.2-20 Although specific immune tests do not always correlate with disease severity, nor is any single test always abnormal, they become more valuable when used as an array or set of tests used to determine a pattern of immune dysfunction.

Tests of Immunity T-cell activation

1. IL-2 receptor, T8-receptor -elevated
2. One and two-color flow cytometry
  • CD3/DR, CD8/DR - elevated
  • CDllb, CD8/CDllb - depressed
  • CD3 - elevated
  • CD56 - elevated
  • CD4/CD45R - depressed
  • CD20 elevated (3) 
  • Interferon-alpha, IL-1-alpha - elevated (4) 
  • Intracellular 2-5A, Rnase-L antiviral activity - elevated
Discrete Immune Defects
  1. Hypogammaglobulinemia (IgG)
  2. IgG subclass deficiencies
  3. Anergy and hypoergy by epicutaneous skin testing
  4. Mitogen stimulation deficiencies (T and B cell deficiencies)
  5. Natural Killer (NK) cytotoxic deficiencies
  6. Circulating immune complexes

Viral Activation or Re-activation

Viral activity or activation is suggested in CFS due in part to the abrupt onset of a flu-like, mono-like, or encephalitic-like illness which usually precedes the development of this disorder, its signs and symptoms over time, and the nature of the immune response observed. The common symptoms of debilitating fatigue, swollen glands, sore throat, and headache have suggested re-activation of mono-causing herpes viruses (EBV, HHV-6, or CMV), which are usually contracted much earlier in life. It is probable that these lymphotropic herpes viruses are involved in most cases of CFS but are not the cause of CFS. It is likely that they are merely reflecting T-cell activation itself or loss of immunologic control of these viruses due to a state of immune deficiency by whatever cause. It is conceivable that an as-yet-unknown virus has initiated CFS much as HIV initiates AIDS. Such a virus is likely to be subtle, immunotropic, and neurotropic. Retroviruses are all of these things, and attention has focused on them in recent years.

The following is a set of tests that look for evidence of re-activation of herpes-group viruses as well as evidence of a possible retrovirus infection. The retroviral assays include DNA amplification technology and evidence of non-specific cytopathic effects in cell culture consistent with a family of retroviruses recently associated with CFS. Again, more important than the results of a single test is the pattern of herpes-group virus re-activation, evidence of retroviral gene sequences, and evidence of retroviral cytopathology in nonspecific culture assays, all of which support the role of viral activation in CFS. Whether this activity is cause or effect, however, is still open to question. It should be noted that lymphotropic herpes viruses and retroviruses can activate or transactivate each other and are therefore synergistic.

Tests of Viral Activation or Re-activation Herpes-Group Virus Assays 21-26
  1. Antibody assays for EBV, HHV-6, CMV, HSV-1,2 & VZ looking for elevated titers consistent with recent activity.
  2. Viral DNA amplification for EBV, HHV-6, and CMV using the polymerase chain reaction (PCR), with positive results suggesting viral activity.
  3. Giant cell assays with monoclonal labeling for various herpes-group viruses, with positive results suggesting such viral activity.

Retrovirus Assays 27-30
  1. Cytopathology in fibroblast cell lines consistent with human foamy retroviruses or human intracisternal retroviruses
  2. HTLV-II gag probes, run using low-stringency PCR to detect retroviral gene sequences present in CFS patients which are HTLV-II-like but not HTLV-II. This test will likely give way to specific probes based on conserved sequences of actual retroviral isolates of whatever family cultured from CFS patients.
Exercise-Related Dysfunction

Patients with CFS describe characteristic worsening of their symptoms following exercise as well as exercise limitations. Exercise ergometry with gas analysis has proven useful in CFS to document defects in functional capacity; a functional consequence of debilitating fatigue. Several reports have attracted further interest in this technology as a diagnostic instrument for showing neuroendocrine defects in response to exercise, 31 as well as defects in respiratory control mechanisms within the central nervous system in CFS patients.

Bicycle ergometry with gas analysis has proven useful to document disability in CFS and will likely prove useful to document deep brain dysfunction characteristic of CFS patients.

Tests of Exercise-Related Dysfunction Important measurements using bicycle ergometry with gas analysis
  1. Peak oxygen consumption at maximum exertion
  2. Work rate at anaerobic threshold as against peak work rate.
  3. Oxygen consumption at anaerobic threshold
  4. Work efficiency - independent of conditioning
  5. Breath-to-breath tidal volume variance at peak exercise
Brain Dysfunction

Perhaps no set of symptoms is more disturbing to CFS patients nor more striking to clinicians than the neurocognitive complaints seen in CFS. They characteristically evolve slowly over time and often grow to dominate the clinical scene. At first there is only the mental "fog" of a viral syndrome, but this slowly gives way to the more worrisome complaints of memory disturbance, word searching, processing speed, and spatial disorganization. There also may be neuropsychological complaints including panic attacks, depression, and mood swings. Evidence of characteristic abnormalities on neuropsychometric tests and characteristic profiles on the MMPI have been reported.32,33 Defects on structural34,35 (MRI) and functional scans (SPECT and Topographic Computer EEC) of the brain have also been reported.36,37 As mentioned above, soft neurologic findings are also frequently demonstrated under physical examination. We have proposed a number of approaches to document evidence of brain dysfunction in CFS.

Tests to Document Brain Dysfunction

Structural Scans - MRI is recommended for any patient with an abnormal neurologic examination or significant neurologic symptoms. This is done primarily to rule out structural abnormalities which might mimic CFS signs and symptoms. Many CFS patients (50 percent or more) will exhibit small punctate areas of increased signal, usually in subcortical white matter areas.

Functional Scans - SPECT scans, which primarily measure blood flow, are frequently abnormal (80 to 85 percent), showing areas of decreased perfusion primarily in the temporal and frontal lobes.

Topographic computer EEC brain mapping has shown increased slow-wave activity usually in the anterior leads and especially when patients are engaged in certain cognitive tasks. This usually diffuse slow-wave activity strongly suggests metabolic or toxic encephalopathy.

Neuropsychometric Testing - A complete Halstead Reitan battery or subsets of this battery form the basis of determining the nature and extent of cognitive impairment in CFS. Patients will exhibit characteristic focal and multifocal deficits in which performance on certain subtests will be normal or even well above normal while performance on certain other subtests will be substantially below normal. Performance deficits appear to occur more frequently in particular subtests of this battery.

Knowledge Is Power

CFS clinical and bench researchers are developing an array of tests which are increasingly sensitive and specific for CFS — particularly when used in combination. When patients present with symptoms that suggest CFS, we believe it is in their best interest to selectively employ these tests to confirm the diagnosis and to document the nature and extent of each case. This information: increases both the physician's and patient's confidence in the diagnosis and their ability to track the course of the disease; enables the patient to make appropriate lifestyle adjustments (including defense of disability claims when necessary); and provides the physician with a basis for therapeutic intervention.

References

1. Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, Jones JF, Dubois RE, Cunningham-Rundles C, Pahwa S, Tosato G, Zegan SLS, Purtilo DT, Brown N, Schooley RT, Brus I. Chronic fatigue syndrome: a working case definition. Ann of Int Med, 108:387-9, 1988
2. Klimas N, Salvato F, Morgan R, abnormalities in chronic fatigue syndrome. J of Clin Micro, 28:1403-10, 1990
3. Lloyd AR, Wakefield D, Boughton CR, Dwyer JM. Immunological abnormalities in the chronic fatigue syndrome. M J of Australia, 151(3):122-4, 1989
4. Caligiuri M, Murray C, Buchwald D, Levine H, Cheney PR, Peterson D, Komaroff AL, Ritz J. Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome. J Immun 139:3306-13, 1987
5. Aoki T, Usuda Y, Miyakoshi H, Tamura K, Herberman RB. Low natural killer syndrome: clinical and immunologic features. Cat Immun Cell Growth Regul, 6:116-128, 1987
6. Tosato G, Straus S, Henle W, Pike SE, Blaese RM. Characteristic T cell dysfunction in patients with chronic active Epstein-Barr virus infection (chronic infectious mononucleosis). J Immunol 134:3082-8, 1985
7. Prieto J, Subir'a ML, Castilla A, Serrano M. Naloxone reversible monocyte dysfunction in patients with chronic fatigue syndrome. Scan J Immunol. 30(1)-.13-20, 1989
8. Salvato F, Fletcher M, Ashman M, Klimas N. Immune dysfunction among chronic fatigue syndrome (CFS) patients with clear evidence of Epstein-Barr virus (EBV) reactivation. J Exp Clin Cancer Res, (sup)7:89, 1988
9. Linde A, Hammarstrom L, Smith C. IgG subclass deficiency and chronic fatigue syndrome. Lancet i:885-6, 1988
10. Komaroff AL, Geiger AM, Wormseley S. IgG subclass deficiencies in chronic fatigue syndrome. Lancet i(8597):1288-9, 1988
JL1. Read R, Spickett G, Harvey J, Edwards AJ, Larson HE. IgG 1 subclass deficiency in patients with chronic fatigue syndrome. Lancet, i:241-2, 1988
12. Franco E, Kawa-ha K, Doi S, Yumura K, Murata M, Ishihara S, Tawa A, Yabuuchi H. Remarkable depression of CD4+2H4+T cells in severe chronic active Epstein-Barr virus infection. Scan J Immunol 26:769-73, 1987
13. Cheney PR, Rozovsky I. The relationship of soluble IL-2 receptor to functional capacity in CFS. The CFIDS Association 1990 CFIDS Research Conference, "Unravelling the Mystery," Nov. 17-18, 1990, Charlotte, NC.
14. Subira ML, Castilla A, Civeira MP. Deficient display of CD3 on lymphocytes of patients with chronic fatigue syndrome [Letter] J Infect Dis 60(l):165-6, July,1989.
15. Levy J, et al. Chronic fatigue syndrome: clinical condition associated with immune activation. Lancet Vol.338, No.8769, Sept. 1991
16. Biron, et al. Severe herpesvirus infections in an adolescent without natural killer cells. NE J Med 320: 1731-5, June 29, 1989
17. Morte S, Castilla A, Iveira MP, Serrano M, Prieto J. Production of interleukin-1 by peripheral blood mononuclear cells in patients with chronic fatigue syndrome [Letter]. J Infect Dis, 159:362, 1989
18. Straus SE, Dale JK, Peter JB, Dinarello CA. Circulating lymphokine levels in the chronic fatigue syndrome [Letter]. J Infect Dis, 160(6):1085-6 1989
19. Cheney PR, Dorman SE, Bell DS. Interleukin-2 and the chronic fatigue syndrome [Letter]. Ann Int Med 110:321 1989
20. Linde A, Anderson B, Svenson SB, Ahrne H, Carlsson M, Forsberg P, Hugo H, Karstop A, Lenkei R, Lindwall A, Loftenius A, Sail C, Anderson J. Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome. J Infect Dis, 165:994-1000, 1992
21. Buchwald D, Freedman A, Ablashi D, Sullivan J, Caliguiguri M, Weinberg D, Hall C, Ashley R, Saxinger C, Balachandran N, Ritz J, Nadler L, Komaroff AL. A chronic postinfectious fatigue syndrome associated with benign lymphoproliferation, B-cell proliferation, and active replication of human herpesvirus-6. J Clin Immun, 10(6):335-344, 1990
22. Komaroff AL. Human herpesvirus-6 and human disease. Am J Clin Pathol, 93:836-7, 1990
23. Steeper TA, Horwitz CA, Ablashi DV, et al. The spectrum of clinical and laboratory findings due to human herpesvirus-6 (HHV-6) in patients with mononucleosis-like illnesses not due to EBV or CMV. Am J Clin Pathol, 93:836-7, 1990
24. Tobi M, Moraq A, Ravid Z, Chowers I, Feldman-Weiss V, Mitchell Y, Chetrit E Ben, Shalit M, Knobler H. Prolonged atypical illness associated with serological evidence of persistent Epstein-Barr virus infection. Lancet, 1:61-4, 1982
25. Jones JF, Ray CG, Minnich LL, Hicks MJ, Kibler R, Lucas DO. Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses; elevated anti-early antigen antibodies. Ann Int Med 102:1-7, 1985
26. Straus SE, Tosato G, Armstrong G, Lawley T, Preble OT, Henle W, Davey R, Pearson G, Epstein J, Brus I, Blaese RM. Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection. Ann Int Med, 102:7-16, 1985
27. DeFreitas E, Billiard B, Cheney PR, Bell DS, Kiggundu E, Sankey D, Wroblewska Z, Palladino M, Woodward JP, Koprowski H. Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome. Proc Natl Acad Sci USA, Vol.88, mpp.2922-26, April 1991
28. Bothe K, Aguzzi A, Lassmann H, Rethwilm A, Horak I. Progressive encephalopathy and myopathy in transgenic mice expressing human foamy virus genes. Science, Vol.253, pp. 555-567, August, 1991
29. Cameron KR, Bircham SM. Moss MA. Isolation of foamy virus from patient with dialysis encephalopathy: Lancet p. 796, October 7, 1978
30. Weiss RA. A virus in search of a disease. Nature, Vol.333, June 9, 1988
31. Daly J. The ventilatory response to exercise in CFS. The Third Annual Conference - Chronic Fatigue Syndrome and the Brain, Bel-Air, California, April 24-26, 1992
32. Onischenko T. It's all in your head - well, indeed it is... The Third Annual Conference - Chronic Fatigue Syndrome and the Brain, Bel-Air, California, April 24-26, 1992
33. Iger, LM. Changes on the CFS profile with the MMPI-2. The Third Annual Conference - Chronic Fatigue Syndrome and the Brain, Bel-Air, California, April 24-26, 1992
34. Daugherty SA, Henry BE, Peterson DL, Swarts RL, Bastien S, Thomas RS. Chronic fatigue syndrome in northern Nevada. Rev Infect Dis, 13{Supp l):S39-44, 1991 (MRI Scans)
35. Buchwald D, Cheney PR, Peterson DL, Henry B, Wormsley SB, Geiger A, Abalashi DV, Salahuddin Z, Saxinger C, Biddle R, Kikinis R, Jolesz FA, Folks T, Balachandran N, Peter JB, Gallo RC, Komaroff AL. A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus-6. Ann Int Med, Vol.116,(2), pp.103-113, January 15, 1992
36. Mena I. Study of cerebral perfusion by NeuroSpect in patients with chronic fatigue syndrome. Symposium on Myalgic Encephalomyelitis, p.21, Cambridge, England, April 1990 (SPECT Scans)
37. Cheney PR, et al. CFS: A clinical perspective on the use of MEG and EEC brain mapping. The Third Annual Conference - Chronic Fatigue Syndrome and the Brain, Bel-Air, California, April 24-26, 1992
This is what oral Kaposi's Sarcoma looks like.




Source: https://doctorspiller.com/kaposis-sarcoma/

Compare it to these crimson crescent lesions in the mouths of Chronic Fatigue Syndrome patients.



"Burke A. Cunha, MD, discovered what he called crimson crescents in the mouths of 80% of his CFS patients. After the word got out, Cunha received calls from other parts of the country. Physicians began telling him that they also were finding the crimson crescents in their patients once they looked for them."

https://www.prohealth.com/library/crimson-crescents-facilitate-chronic-fatigue-syndrome-cfs-diagnosis-11266




Chronic Fatigue Syndrome patients may have undiagnosed internal Kaposi's Sarcoma. Susan Levin found HHV-8, the Kaposi's Sarcoma virus, in half of CFS patients she looked at.

Prevalence in the Cerebrospinal Fluid of the Following Infectious Agents in a Cohort of 12 CFS Subjects

Susan Levine

Published online: 04 Dec 2011


Over the last decade a wide variety of infectious agents has been associated with the chronic fatigue syndrome (CFS) as potential etiologies for this disorder by researchers from all over the world. Many of these agents are neurotrophic and have been linked previously to other diseases involving the central nervous system (CNS). Human herpes virus-6 (HHV-6), especially the B variant, has been found in autopsy specimens of patients who suffered from multiple sclerosis. Because patients with CFS manifest a wide range of symptoms involving the CNS as shown by abnormalities on brain MRIs, SPECT scans of the brain and results of tilt table testing we sought to determine the prevalence of HHV-6, HHV-8, Epstein-Barr virus (EBV), cytomegalovirus (CMV), Mycoplasma species, Chlamydia species, and Coxsackie virus in the spinal fluid of a group of 12 patients with CFS. Although we intended to search mainly for evidence of actively replicating HHV-6, a virus that has been associated by several researchers with this disorder, we found evidence of HHV-8, Chlamydia species, CMV and Coxsackie virus in 6/12 samples. Attempts were made to correlate the clinical presentations of each of these patients, especially the neurological exams and results of objective testing of the CNS, with the particular infectious agent isolated. It was also surprising to obtain such a relatively high yield of infectious agents on cell free specimens of spinal fluid that had not been centrifuged. Future research in spinal fluid analysis, in addition to testing tissue samples by polymerase chain reaction (PCR) and other direct viral isolation techniques will be important in characterizing subpopulations of CFS patients, especially those with involvement of the CNS.

https://www.tandfonline.com/doi/abs/10.1300/J092v09n01_05






Is Chronic Fatigue Syndrome Associated Kaposi's Sarcoma (CFSKS) a diagnosis all doctors should become aware of?

Another HHV-8- associated condition, the KSHV inflammatory cytokine syndrome (KICS), has been more recently described.48-50 Patients with this syndrome display MCD-like inflammatory symptoms, but do not have pathological findings of MCD. Patients with KICS are frequently critically ill and demonstrate marked elevations in IL-6 and IL-10, as well as high plasma HHV-8 viral loads. KICS may contribute to the inflammatory symptoms seen in some patients with severe KS or PEL, and there may be significant clinical overlap between these conditions. 

https://aidsinfo.nih.gov/guidelines/html/4/adult-and-adolescent-opportunistic-infection/342/hhv-8




Chronic Fatigue Syndrome patients may have undiagnosed internal Kaposi's Sarcoma.

Prevalence in the Cerebrospinal Fluid of the Following Infectious Agents in a Cohort of 12 CFS Subjects

Susan Levine

Published online: 04 Dec 2011


Over the last decade a wide variety of infectious agents has been associated with the chronic fatigue syndrome (CFS) as potential etiologies for this disorder by researchers from all over the world. Many of these agents are neurotrophic and have been linked previously to other diseases involving the central nervous system (CNS). Human herpes virus-6 (HHV-6), especially the B variant, has been found in autopsy specimens of patients who suffered from multiple sclerosis. Because patients with CFS manifest a wide range of symptoms involving the CNS as shown by abnormalities on brain MRIs, SPECT scans of the brain and results of tilt table testing we sought to determine the prevalence of HHV-6, HHV-8, Epstein-Barr virus (EBV), cytomegalovirus (CMV), Mycoplasma species, Chlamydia species, and Coxsackie virus in the spinal fluid of a group of 12 patients with CFS. Although we intended to search mainly for evidence of actively replicating HHV-6, a virus that has been associated by several researchers with this disorder, we found evidence of HHV-8, Chlamydia species, CMV and Coxsackie virus in 6/12 samples. Attempts were made to correlate the clinical presentations of each of these patients, especially the neurological exams and results of objective testing of the CNS, with the particular infectious agent isolated. It was also surprising to obtain such a relatively high yield of infectious agents on cell free specimens of spinal fluid that had not been centrifuged. Future research in spinal fluid analysis, in addition to testing tissue samples by polymerase chain reaction (PCR) and other direct viral isolation techniques will be important in characterizing subpopulations of CFS patients, especially those with involvement of the CNS.

https://www.tandfonline.com/doi/abs/10.1300/J092v09n01_05


If HHV-8 (which seems to cause Castleman Disease) really is African Swine Fever then pigs will make an excellent model for studying Castleman Disease. Is this an indication that HHV-8 is really African Swine Fever Virus?

"Primary HHV-8 infection may be associated with fever and a maculopapular rash in immunocompetent children."

http://www.uptodate.com/contents/disease-associations-of-human-herpesvirus-8-infection

High prevalence of antibodies to human herpesvirus 8 in relatives of patients with classic Kaposi's sarcoma from Sardinia.


http://www.ncbi.nlm.nih.gov/pubmed/9607855


Infection with human herpesvirus type 8 and Kaposi's sarcoma in Sardinia.

 http://www.ncbi.nlm.nih.gov/pubmed/16501902

 

 Epidemiology of HHV8 in Sardinian emigrants

 http://www.dsnm.univr.it/?ent=progetto&id=565

 Both ASFV and HHV-8 Interfere with apoptosis.

Are ASFV-infected Pigs the viral source of HHV-8 related Kaposi's Sarcoma in Sardinia? Is a ASFV-related Kaposi's Sarcoma epidemic possible in Russia where ASFV is spreading?

 https://hhv6.jottit.com/35._pigs_and_kaposi%27s_sarcoma_in_sardinia

The world's highest incidence of Kaposi's sarcoma occurs in Sardinia (Reference) Is it possible that it is due to the fact that African Swine Fever Virus is endemic on the island? (Reference) One study suggests that the incidence of K.S. in northern Sardinia is highest in a countryside area where people have contact with animals. (Reference) Given the high prevalence of HHV-8,--the so-called K.S. herpes virus--in Sardinia (Reference) is it at all possible that HHV-8 may have been misclassified and actually is a human-adapted form of African Swine Fever Virus? (ASFV has been at least visually mistaken for another herpes virus, CMV, in the past.)

A number of experiments could be conducted to explore this hypothesis. In addition to a direct comparison of ASFV and HHV-8, pigs with African Swine Fever Virus could be tested for sequences of HHV-8. People with Kaposi's sarcoma could be tested for sequences of African Swine Fever, including new Asfaviridae sequences recently discovered. (Reference) 

A comparison of the K.S. lesions in humans and ASFV lesions in pigs might be in order.Given that African Swine Fever is currently spreading in Russia and is now threatening Europe and China, (Reference) it would be useful to know whether people who are exposed to pigs with ASFV are at increased risk for HHV-8, Kaposi's sarcoma and the other pathologies associated with HHV-8. A study in sub-Saharan Africa where ASFV is endemic and HHV-8 is also endemic (Reference) might be useful. And areas of Russia where ASFV is spreading could be monitored closely for any signs of an increase of K.S. or HHV-8 infection and HHV-8 related pathologies.HHV-8 is an emerging health problem. HHV-8-associated K.S. is a significant problem in AIDS patients. It may also be the key to Chronic Fatigue Syndrome. HHV-8 has been found in the cerebrospinal fluid of 50% of Chronic Fatigue Syndrome patients. (Reference) HHV-8 has been linked to type 2 diabetes. (Reference) HHV-8 has been detected in B-cells in Castleman's disease and primary effusion lymphoma. (Reference).

If HHV-8 is a form of ASFV, it is possible that pigs might constitute a useful animal model for the study of possible treatments for K.S. and other pathologies associated with HHV-8. And if there is any relationship between ASFV and HHV-8, people may have to be warned to take special precautions around pigs in areas where there are ASFV outbreaks. And countries where undercooked pork is consumed (like Ukraine where salo is a staple) may need to alert the public to cook all pork products thoroughly during ASFV epidemics.

 

A number of years ago, Neenyah Ostrom reported in the New
York Native on the lesions in CFS patients which seem
to resemble Kaposi's Sarcoma (KS). The current
thinking is that a virus called HHV-8 is the cause of
KS. (Although HHV-6 has recently also been implicated
once again.) If KS is a problem in CFS (and we
suspect it is) then one should be able to find HHV-8 and
HHV-6 in CFS patients. Apparently, in this small
study, one can. Below is a rather explosive abstract:
Prevalence in the cerebrospinal fluid of the following
infectious agents in a cohort of 12 CFS subjects:
human herpes virus-6 and 8; chlamydia species;
mycoplasma species; EBV; CMV; and Coxsackievirus.
Levine, S.
Journal of Chronic Fatigue Syndrome, 2001, 9, 1/2,
41-51.
Abstract:
Over the last decade a wide variety of infectious
agents have been associated with the CFS as potential
etiologies for this disorder. Many of these agents are
neurotrophic and have been linked previously to other
diseases involving the central nervous system (CNS).
Human herpes virus-6 (HHV-6), especially the B
variant, has been found in autopsy specimens of
patients who suffered from MS. Because patients with
CFS manifest a wide range of symptoms involving the
CNS as shown by abnormalities on brain MRIs, SPECT
scans of the brain and results of tilt table testing
we sought to determine the prevalence of HHV-6, HHV-8,
Epstein-Barr Virus (EBV), cytomegalovirus (CMV),
mycoplasma species, chlamydia species, and Coxsackie
virus in the spinal fluid of a group of 12 patients
with CFS (CDC criteria '94).
We found evidence of HHV-6, HHV-8, chlamydia species,
CMV and Coxsackie virus in 6/12 samples. Plasma tests
were negative. It was surprising to obtain such a
relatively high yield of infectious agents in cell
free specimens of spinal fluid that had not been
centrifuged. Future research in spinal fluid analysis,
in addition to testing tissue samples by polymerase
chain reaction (PCR) and other direct viral isolation
techniques will be important in characterizing
subpopulations of CFS patients, especially those with
involvement of the CNS.
The low rate of isolation of HHV-6 may be related to
the lack of gross neurological findings in the
patients at the time of testing.
An overview of KS:http://www.thebody.com/nmai/ks.html
Except for those who have made a lifelong commitment
to denial, finding the so-called "KS virus" (HHV-8)
and the "supporting KS virus" (HHV-6) in CFIDS patients
should help settle the question of the overlapping
nature of the AIDS and CFIDS epidemics.
Isn't it time to take a closer look at those crimson
crescents in the throats of CFIDS patients?
More info on KS here.

Given that HHV-8 is part of the HHV-6 and HHV-7 family, this may be very important:

"The 19R Protein of HHV-6 has significant amino acid sequence homology . . . to a protein encoded by African Swine Fever Virus."

--Glenda L. Lawrence, John Nicholas and Bart G. Barrell
Journal of General virology (1995), 76, 147-152

 Click here for more information on this issue.

  animal model, asfv, cdc, HHV-6, hhv-7, HHV-8, pigs, PLHV, porcine herpesvirus, swine

 

 



A documentary about the transmission of Chronic Fatigue Syndrome between people and their pets.




Charles Ortleb discusses the 1998 research by Dr. Thomas Glass on the possible transmission of Chronic Fatigue Syndrome between people and their pets. He also reads from an article by Neenyah Ostrom published eight years earlier in his newspaper, New York Native. Ostrom reported on a woman with Chronic Fatigue Syndrome whose sick dog tested positive for HHV-6, the virus that in increasingly being linked to Chronic Fatigue Syndrome.




Did Chronic Fatigue Syndrome come from pigs? Will pigs make the best animal model for Chronic Fatigue Syndrome?



Antibody Cross-Reactivity between Porcine Cytomegalovirus (PCMV) and Human Herpesvirus-6 (HHV-6)

http://www.mdpi.com/1999-4915/9/11/317

Porcine cytomegalovirus (PCMV) infection is widely prevalent among pigs, and PCMV is one of the viruses which may be transmitted during xenotransplantation using pig cells, tissues, or organs. While human cytomegalovirus (HCMV) is a major risk factor for allotransplantation, it is still unclear whether PCMV is able to infect human cells or pose a risk for xenotransplantation. Previously, it was shown that transmission of PCMV after pig kidney to non-human primate transplantations resulted in a significantly reduced survival time of the transplanted organ. To detect PCMV, PCR-based and immunological methods were used. Screening of pigs by Western blot analyses using recombinant viral proteins revealed up to 100% of the tested animals to be infected. When the same method was applied to screen human sera for PCMV-reactive antibodies, positive Western blot results were obtained in butchers and workers in the meat industry as well as in normal blood donors. To exclude an infection of humans with PCMV, the sera were further investigated. PCMV is closely related to human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7), and a sequence alignment of glycoprotein B suggests that the antibodies may cross-react with identical epitope sequences. HCMV is not related with PCMV, and no correlation between antibody reactivity against PCMV and HCMV was detected. These data indicate that antibodies against PCMV found in humans are cross-reactive antibodies against HHV-6. View Full-Text


Will a porcine animal model using HHV-6 be useful for Chronic Fatigue Syndrome? 

Dr. Serge Barcy
Dr. Serge Barcy has recently identified and begun to characterize two new homologs of HHV-6 and HHV-7 which naturally infect pig-tailed macaques. He has already reported that the blood prevalence and tissue tropism of MneHV6 and MneHV7 are similar to that seen with HHV6 and HHV7 in humans. Using these animals as a nonhuman primate model of HHV-6 and HHV-7 natural infection.


http://www.seattlechildrens.org/research/science-industry-partnerships/partnership-opportunities/hhv-human-herpesvirus/

2014 Dec;471-473:126-40. doi: 10.1016/j.virol.2014.10.008. Epub 2014 Oct 31.

Discovery and biological characterization of two novel pig-tailed macaque homologs of HHV-6 and HHV-7.

Abstract

Human herpesvirus-6 (HHV-6) and -7 (HHV-7) are Roseoloviruses within the Betaherpesvirus family, which have a high prevalence and suspected involvement in a number of diseases. Using CODEHOP-based PCR, we identified homologs of both viruses in saliva of pig-tailed macaques, provisionally named MneHV-6 and MneHV-7. This finding supports the existence of two distinct Roseolovirus lineages before the divergence of humans and macaques. Using specific qPCR assays, high levels of MneHV-6 and MneHV-7 DNA were detected in macaque saliva, although the frequency was greater for MneHV-7. A blood screen of 283 macaques revealed 10% MneHV-6 DNA positivity and 25% MneHV-7 positivity, with higher prevalences of MneHV-6 in older females and of MneHV-7 in younger males. Levels of MneHV-6 were increased in animals coinfected with MneHV-7, and both viruses were frequently detected in salivary gland and stomach tissues. Our discovery provides a unique animal model to answer unresolved questions regarding Roseolovirus pathology.

The existence of roseolovirus homologs in non-human primates had been suggested based on serological data (Higashi et al., 1989). Attempts to find HHV-6-like sequences in pig-tailed macaques by HHV-6-specific PCR failed, which led to the assumption that these animals are not commonly infected by a virus related to HHV-6 (Lusso et al., 1994a). Our studies clearly show that pig-tailed macaques are naturally infected with two distinct roseoloviruses closely related to HHV-6 and HHV-7, suggesting that MneHV-6 and MneHV-7 infections in macaques would be an important non-human primate model of roseolovirus infections and pathology. Taken together, our discovery and initial analysis of two novel roseolovirus homologs in macaques offers a unique opportunity to develop relevant animal models using viruses native to the host to answer various unresolved questions surrounding their biology and respective roles as etiological agents in diseases.

2016 Jul 11;90(15):6657-6674. doi: 10.1128/JVI.00651-16. Print 2016 Aug 1.

Complete Unique Genome Sequence, Expression Profile, and Salivary Gland Tissue Tropism of the Herpesvirus 7 Homolog in Pigtailed Macaques.

Abstract

Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses and are highly prevalent in the human population. Roseolovirus reactivation in an immunocompromised host can cause severe pathologies. While the pathogenic potential of HHV-7 is unclear, it can reactivate HHV-6 from latency and thus contributes to severe pathological conditions associated with HHV-6. Because of the ubiquitous nature of roseoloviruses, their roles in such interactions and the resulting pathological consequences have been difficult to study. Furthermore, the lack of a relevant animal model for HHV-7 infection has hindered a better understanding of its contribution to roseolovirus-associated diseases. Using next-generation sequencing analysis, we characterized the unique genome of an uncultured novel pigtailed macaque roseolovirus. Detailed genomic analysis revealed the presence of gene homologs to all 84 known HHV-7 open reading frames. Phylogenetic analysis confirmed that the virus is a macaque homolog of HHV-7, which we have provisionally named Macaca nemestrina herpesvirus 7 (MneHV7). Using high-throughput RNA sequencing, we observed that the salivary gland tissue samples from nine different macaques had distinct MneHV7 gene expression patterns and that the overall number of viral transcripts correlated with viral loads in parotid gland tissue and saliva. Immunohistochemistry staining confirmed that, like HHV-7, MneHV7 exhibits a natural tropism for salivary gland ductal cells. We also observed staining for MneHV7 in peripheral nerve ganglia present in salivary gland tissues, suggesting that HHV-7 may also have a tropism for the peripheral nervous system. Our data demonstrate that MneHV7-infected macaques represent a relevant animal model that may help clarify the causality between roseolovirus reactivation and diseases.

IMPORTANCE:

Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses. We have recently discovered that pigtailed macaques are naturally infected with viral homologs of HHV-6 and HHV-7, which we provisionally named MneHV6 and MneHV7, respectively. In this study, we confirm that MneHV7 is genetically and biologically similar to its human counterpart, HHV-7. We determined the complete unique MneHV7 genome sequence and provide a comprehensive annotation of all genes. We also characterized viral transcription profiles in salivary glands from naturally infected macaques. We show that broad transcriptional activity across most of the viral genome is associated with high viral loads in infected parotid glands and that late viral protein expression is detected in salivary duct cells and peripheral nerve ganglia. Our study provides new insights into the natural behavior of an extremely prevalent virus and establishes a basis for subsequent investigations of the mechanisms that cause HHV-7 reactivation and associated disease.

If you have Amazon Prime or Kindle Unlimited you can immediately begin reading this book that discusses the relationship between Chronic Fatigue Syndrome, pets, and pigs.


If you have Amazon Prime or Kindle Unlimited, you can immediately begin reading The Chronic Fatigue Syndrome Epidemic Cover-up and you will soon understand why the facts about the Chronic Fatigue Syndrome epidemic have been hidden from the public for almost four decades.









This is the book causing heated debates about Chronic Fatigue Syndrome and HHV-6, "The Fifty Shades of AIDS Virus," in laboratories, doctor's offices, and homes all over the world.

                                                              


In his bestselling book, The Black Swan, Nassim Nicholas Taleb wrote, "I see the risks of a very strange acute virus spreading throughout the planet." This book by Charles Ortleb warns that the virus causing Chronic Fatigue Syndrome is that virus.

This book belongs in the library of anyone who wants to know the disturbing history of the Chronic Fatigue Syndrome epidemic and the deadly virus HHV-6. Why have the CDC and NIH pretended that the communicable disease fraudulently called "Chronic Fatigue Syndrome" is a mystery for over three decades? By the end of this book of inconvenient truths the answer is crystal clear. The shocking news and bold analysis in this page-turner could lead to a revolution in the science and politics of Chronic Fatigue Syndrome, fibromyalgia, AIDS, autism, and many other illnesses. Scientists, doctors, nurses, patients, journalists, politicians, and historians must begin their journey to a full understanding of the Chronic Fatigue Syndrome epidemic with this book.

As the publisher and editor-in-chief of a small newspaper in New York, Charles Ortleb was the first journalist to devote a publication to uncovering the truth about Chronic Fatigue Syndrome. He assigned Neenyah Ostrom the duty of following every twist and turn of the Chronic Fatigue Syndrome story. No newspaper in the world did more to warn the world about the virus which seems to be triggering Chronic Fatigue Syndrome and many other immunological disorders. Chronic Fatigue Syndrome and AIDS are just the tip of the HHV-6 iceberg.

This provocative book will end the injustice of the silent treatment Neenyah Ostrom's reporting has been getting from the media and The Chronic Fatigue Syndrome community. Ostrom blew the lid off one of the biggest medical secrets of our time: the link between the Chronic Fatigue Syndrome epidemic and AIDS.

Ostrom interviewed most of the major researchers in the field, as well as countless patients and government scientists. She uncovered so many similarities between Chronic Fatigue Syndrome and AIDS that she came to the conclusion that they are part of the same epidemic, and she argued that until their connection is admitted by top government researchers, there is little hope of making real progress in the fight against Chronic Fatigue Syndrome.

Charles Ortleb's book captures all the challenges and excitement of running a small newspaper that was publishing a brilliant journalist who essentially was the Woodward and Bernstein of the Chronic Fatigue Syndrome epidemic. In Rolling Stone, David Black said Ortleb's newspaper deserved a Pulitzer Prize. Randy Shilts praised Ortleb's newspaper in And the Band Played On.

                                                            


This book continues the work Ortleb has been doing to raise awareness about HHV-6 and Chronic Fatigue Syndrome at his website HHV-6 University. Fewer and fewer people now pretend that HHV-6 is harmless. Thanks to Ortleb's efforts, more and more people are abandoning HHV-6 denialism and admitting the virus is at the center of a public health disaster.

 Hillary Johnson, the author of Osler's Web, called it "A rollicking, fascinating and important memoir."





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