Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a disease of unknown aetiology. A patient with CFS had unexpected, marked recovery of CFS symptoms lasting for five months during and after cytotoxic chemotherapy for Hodgkin’s disease. We reasoned that the transient CFS recovery was related to methotrexate treatment, which induces immunomodulation in part through B-cell depletion.

METHODS: In a case series, this patient and two additional CFS patients were B-cell depleted by infusion of the monoclonal anti-CD20 antibody rituximab.

RESULTS: All three had improvement of all CFS symptoms. Patients 1 and 2 had major amelioration from 6 weeks after intervention, patient 3 slight improvement from the same time, but then improved markedly from 26 weeks after intervention. The symptomatic effect lasted until weeks 16, 18 and 44, respectively. At relapse, all were retreated with a single (patient 1) or double rituximab infusion (patients 2 and 3). Again, all three had marked symptom improvement, mimicking their first response. After new symptom recurrence, patients 1 and 2 were given weekly oral methotrexate, patient 1 having effect also from this agent. Patients 1 and 2 were again treated for a third rituximab infusion after new relapse, again with a marked clinical benefit. No unexpected toxicity was seen.

CONCLUSION: These observations suggest that B-lymphocytes are involved in CFS pathogenesis for a subset of patients. Benefit for all CFS symptoms, the delayed symptom relief following B-cell depletion, the kinetics of relapses, and the effect also from methotrexate treatment, provide suggestive evidence that B-cells play a significant role in the ongoing clinical features, and that CFS may be amenable to therapeutic interventions aimed at modifying B-cell number and function. More systematic investigations of this therapeutic strategy, and of its biological basis, are now needed.

 

Source: Fluge Ø, Mella O. Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series. BMC Neurol. 2009 Jul 1;9:28. doi: 10.1186/1471-2377-9-28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711959/ (Full article)

 

Three cases of dermatomyositis erroneously diagnosed as “chronic fatigue syndrome”

Abstract:

The authors report three cases of dermatomyositis, which ha been erroneously diagnosed as “chronic fatigue syndrome” due to the presence of elevated titers of serum anti-Epstein Barr antibodies.

 

Source: Fiore G, Giacovazzo F, Giacovazzo M. Three cases of dermatomyositis erroneously diagnosed as “chronic fatigue syndrome”. Eur Rev Med Pharmacol Sci. 1997 Nov-Dec;1(6):193-5. http://www.ncbi.nlm.nih.gov/pubmed/9718854

 

Hypnosis in chronic fatigue syndrome

Chronic fatigue syndrome (CFS) is characterized by medically unexplained chronic and disabling physical and mental fatigue. There is growing evidence of organic abnormalities 2 but the involvement of psychological factors in its aetiology and chronicity should also be recognized 3.

One approach to the complaint assumes it is post-viral in origin with psychiatric and social antecedents 4. The sufferer attributes the fatigue and myalgia which persist beyond an initial infectious episode to a continuing viral infection, and interprets them as indicating that activity hinders recovery. A vicious circle is established in which avoidance of activity leads to deconditioning, depression and the perpetuation of symptoms. This view has encouraged the use of cognitive behaviour therapy to increase exercise in graded stages by inducing a more positive attitude towards activity an approach that has met with encouraging results5. Nevertheless, it would seem wrong to attribute CFS entirely to inactivity and sufferers’ illness attributions, if only because there are sufferers who are moderately active and working part-time. Such a model also has difficulty explaining why the symptoms fluctuate within a day, or over longer periods. Furthermore, many sufferers strongly believe that exercise, even in a carefully controlled schedule, will make them feel ill and prolong the complaint. They refuse to contemplate any such therapy 6.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1296740/pdf/jrsocmed00033-0038.pdf

 

Source: Gregg VH. Hypnosis in chronic fatigue syndrome. J R Soc Med. 1997 Dec;90(12):682-3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1296740/

 

Chronic fatigue syndrome: study of the clinical course of 28 cases

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is an entity of unknown etiopathogenesis without specific markers. The diagnosis is based on clinical criteria. There are few studies evaluating the natural evolution and prognosis-related factors in CFS.

OBJECTIVES: a) to evaluate the outcome of patients suffering from CFS, and b) to detect predictive factors associated with a better prognosis.

MATERIAL AND METHODS: Clinical records of all patients diagnosed of CFS between January 1986 and December 1992 were retrospectively reviewed. Of these patients, we included those fulfilling the CDC criteria for CFS, with a follow-up period greater than one year. We evaluated epidemiological, clinical and evolutive data recorded by their usual physicians. Moreover, the patients were interviewed in order to know their own appreciation with respect to their current clinical status, as well as their present working situation.

RESULTS: Twenty-eight patients were included in the present study. Their mean age was 38 +/- 7. Seventy-five percent of them were women. The mean time of clinical follow-up was of 3.2 +/- 1.8 years. According to evaluation, 21% of patients improved or became asymptomatic. A similar percentage (28%) of improvement was obtained from the interview. Forty-eight percent of cases had transitory or definitive laboral incapacity. Regarding to prognostic factors, we could not find any statistical differences among the analyzed variables except for marital status. In this variable, married patients had better outcome than unmarried patients.

CONCLUSION: CFS is an entity with a poor outcome, since it evolves towards to chronicity in an important number of cases. In addition, strong functional disability may be present, leading frequently to laboral incapacity.

Comment in: Chronic fatigue syndrome. To be or not to be? [Med Clin (Barc). 1997]

 

Source: Miró O, Font C, Fernández-Solà J, Casademont J, Pedrol E, Grau JM, Urbano-Márquez A. Chronic fatigue syndrome: study of the clinical course of 28 cases. Med Clin (Barc). 1997 Apr 19;108(15):561-5. [Article in Spanish] http://www.ncbi.nlm.nih.gov/pubmed/9395421

 

Chronic fatigue syndrome/myalgic encephalomyelitis as a twentieth-century disease: analytic challenges

Abstract:

The challenges of chronic fatigue syndrome (often called myalgic encephalomyelitis, especially in the UK) (CFS/ME) to analytical and medical approaches are connected with our inability to understand its distressing somatic symptoms in terms of a single identifiable and understandable disease entity. The evidence for the roles of viral aetiologies remains inconclusive, as does our understanding of the involvement of the immune system.

The history and social context of CFS/ME, and its relation to neurasthenia and psychasthenia are sketched. A symbolic attitude to the condition may need to be rooted in an awareness of psychoid levels of operation, and the expression and spread of CFS/ME may sometimes be aided by the ravages of projective identification. Psychic denial, sometimes violent, in sufferers (especially children and adolescents) and their families may be important in the aetiology of CFS/ME. We draw out common threads from psychodynamic work with five cases, four showing some symptomatic improvement, analytic discussions of three cases being presented elsewhere in this issue of JAP.

 

Source: Simpson M, Bennett A, Holland P. Chronic fatigue syndrome/myalgic encephalomyelitis as a twentieth-century disease: analytic challenges. J Anal Psychol. 1997 Apr;42(2):191-9. http://www.ncbi.nlm.nih.gov/pubmed/9161120

 

Possible correlation between Borna disease virus infection and Japanese patients with chronic fatigue syndrome

Abstract:

Borna disease virus (BDV) is a neurotropic, as yet unclassified, non-segmented, negative-sense, single-strand RNA virus. Natural infection with this virus has been reported to occur in horses and sheep. In addition, antibodies to BDV in plasma or BDV RNA in peripheral blood mononuclear cells (PBMCs) were also found in patients with neuropsychiatric diseases. We describe here the possible link between the patients with chronic fatigue syndrome (CFS) and infection with BDV.

 

Source: Kitani T, Kuratsune H, Fuke I, Nakamura Y, Nakaya T, Asahi S, Tobiume M, Yamaguti K, Machii T, Inagi R, Yamanishi K, Ikuta K. Possible correlation between Borna disease virus infection and Japanese patients with chronic fatigue syndrome. Microbiol Immunol. 1996;40(6):459-62. http://www.ncbi.nlm.nih.gov/pubmed/8839433

 

Chronic fatigue: a peculiar evolution of eosinophilia myalgia syndrome following treatment with L-tryptophan in four Italian adolescents

Abstract:

We describe four Italian adolescents in whom a persistent, debilitating fatigue appeared after therapeutic ingestion of products containing L-tryptophan and subsequent to the development of a transient rise in eosinophil count and severe myalgia (Eosinophilia Myalgia Syndrome-EMS). Their clinical picture was indistinguishable from that of the so-called Chronic Fatigue Syndrome. A chronic fatigue may occur after diverse triggering agents and its represents the peculiar clinical evolution of these four paediatric cases of EMS.

 

Source: Priori R, Conti F, Luan FL, Arpino C, Valesini G. Chronic fatigue: a peculiar evolution of eosinophilia myalgia syndrome following treatment with L-tryptophan in four Italian adolescents. Eur J Pediatr. 1994 May;153(5):344-6. http://www.ncbi.nlm.nih.gov/pubmed/8033924

 

Chronic fatigue syndrome: a joint paediatric-psychiatric approach

Comment in: Chronic fatigue syndrome: a joint paediatric-psychiatric approach. [Arch Dis Child. 1992]

 

Prolonged fatigue after an apparent viral infection, occurring sporadically or as an epidemic, has been described over the past 50 years. It has been given various names including Royal Free disease (1) and myalgic encephalomyelitis, but the preferred terms in the medical literature have been postviral fatigue syndrome (2) or chronic fatigue syndrome (CFS). (3)

However, the validity of this syndrome as a nosological entity has created a good deal of controversy and remains in doubt. (4) A constellation of symptoms make up the syndrome. There is fatigue of defined onset that is generally reported to follow a viral illness, often an influenza-like illness or an infection of the upper respiratory tract. The patient experiences profound fatigue with the initial illness and then fails to make the expected recovery, with fatigue that can persist over months or years. Fatigue is defined as a subjective sensation, which the patient often describes as tiredness or weariness and that occurs at rest. These patients also report a clear relationship of fatigue to activity. The term fatiguability has been used to describe the greater than normal fatigue that occurs after physical and sometimes after mental exertion in these patients. A great variety of associated symptoms have been described that include increased sleepiness, dizziness, vertigo, headache, difficulty in concentrating, sore throat, muscle weakness, and myalgia. The majority of patients have some emotional symptoms. There can be irritability and anxiety, tearfulness and depression. The fatigue and associated symptoms are of such severity as to impair significantly normal daily activities. There is a remarkable absence of physical signs and physical investigations fail to detect any organic pathology or current infection to account for the symptoms.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1793327/pdf/archdisch00639-0088.pdf

 

Source: Vereker MI. Chronic fatigue syndrome: a joint paediatric-psychiatric approach. Arch Dis Child. 1992 Apr;67(4):550-5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1793327/

 

Chronic tiredness and idiopathic chronic fatigue–a connection?

Abstract:

Evidence is adduced to support the proposal that pathological fatigue is a consequence of impaired capillary blood flow resulting in inadequate oxygen delivery, which is in accordance with physiological concepts of fatigue. Case reports are presented.

Comment in: Chronic fatigue syndrome. [N J Med. 1992]

 

Source: Simpson LO. Chronic tiredness and idiopathic chronic fatigue–a connection? N J Med. 1992 Mar;89(3):211-6. http://www.ncbi.nlm.nih.gov/pubmed/1574202

 

Clinical and pathogenetic observations on children with chronic mononucleosis

Abstract:

Epstein-Barr virus is seldom the causative agent of a prolonged atypical illness, known as chronic mononucleosis syndrome, characterized by a persistent pattern of clinical manifestations and by a defective immune response to specific viral antigens. This paper refers about 6 children for whom clinical and serological findings suggest the chronic Epstein-Barr virus infection. The authors believe that this chronic state might be explained by the unusual antibody pattern to EBV virus, with the persistent presence of anti-EA and the absence of anti-EBNA titers, expression of a reduced EBV-specific cytotoxic T cell activity.

 

Source: Cataldo F, Ammatuna P, Bellia L, Sammartano F, Violante M, Albeggiani A. Clinical and pathogenetic observations on children with chronic mononucleosis. Pediatr Med Chir. 1991 Sep-Oct;13(5):489-94. [Article in Italian] http://www.ncbi.nlm.nih.gov/pubmed/1664943