Post traumatic stress disorder and

rheumatic autoimmune diseases

Dr. Enida Xhaferi

Post traumatic stress disorder
• Post-traumatic stress disorder (PTSD) develops
after exposure to a terrifying event in which serious
physical harm occurred or was threatened. It can
arise in people of any age and women are affected
more than men.
• Some events that can trigger this disorder comprise:
accidents, natural or human-caused disasters, violent
personal assaults, combat, rape, diagnosis with a life
threatening disease, severe physical injury,
hospitalization in intensive care unit.

Dr. Enida Xhaferi

 Post traumatic stress disorder
• Rescue workers involved in the aftermath of disasters,
troops who serve in wars and conflicts, survivors of
accidents, physical and sexual abuse, bombing or other
crimes are exposed to highly stressful events and have
increased risk for developing PTSD.
• Victims of disasters are classified in primary casualties,
secondary and tertiary victims (rescue workers and
healthcare providers)

Dr. Enida Xhaferi

Symptoms of PTSD
• Nightmares and flashbacks of past traumatic events
• Avoidance of reminders of trauma
• Emotional numbing
• Severe anxiety
• Fleeing or combative behavior
• Intrusive thoughts
• Detachment from others
• Loss of interest in everyday activities
• Hypervigilance
• Easily startled
• Sleep disturbance
• Social, occupational, and interpersonal dysfunction
• Dissociation
• Self-destructive behavior
• Somatization
• Suicidal behavior
Dr. Enida Xhaferi
Pathophysiology. Biologic factors
• Even thought it is not completely clear studies have
shown that patients with PTSD have smaller volume of
the hippocampus, left amygdala, and anterior cingulate
cortex
• Increased central norepinephrine levels with down-
regulated central adrenergic receptors
• Decreased glucocorticoid levels with up-regulation of
their receptors
• Abnormalities in the opioid system
• Genes may contribute to the disease susceptibility
through an interaction with environmental factors

Dr. Enida Xhaferi

Psychodynamic themes in PTSD
• Trauma may reactivate a previously dormant, unsettled
psychological conflict
• The subjective meaning of a stressor may determine the
nature of the trauma it induces
• Inability to regulate affect can produce trauma.
• Traumatic events can reverberate with childhood traumas
• Somatization and alexithymia (inability to identify and
verbalize feelings) may be the effects of trauma.
• The following defenses are commonly used - denial,
minimization, projective, dissociation, splitting, and guilt.
• Projection and introjection of the following roles : omnipotent
rescuer rescuer, abuser, victim

Dr. Enida Xhaferi

Cognitive factors
• Affected persons cannot manage or rationalize the trauma that lead
to the disorder.
• Trauma (unconditioned stimulus) that produces fear is paired with a
conditioned stimulus (mental reminder of trauma like sight, smell;
through instrumental learning, the conditioned stimuli produces the
fear response independent of the fearful unconditioned stimulus.
The person then avoids both the conditioned stimulus and the
unconditioned stimulus .
• They use avoidance techniques in an attempt to avoid experiencing
their enduring stress.
• Exhibit difficulty retrieving specific memories
• Attention control difficulties
• Gains from the external world (sympathy and monetary
compensation which reinforces the disorder

Dr. Enida Xhaferi

Risk factors for developing PTSD
• Poor family or peer support
• Lower socioeconomic status
• Family or personal history of a psychiatric condition
• Parental neglect
• Severity of initial reaction to the traumatic event
• Perception of an external locus of control not an
internal one
• Neuroticism
• Low IQ

Dr. Enida Xhaferi

 Diagnosis of PTSD with DSM IV criteria
• Criterion A. The person has been exposed to a traumatic event in which both of the following
were present:
1. The person experienced, witnessed or was confronted with an event or events that involved
actual or threatened death or serious injury, or a threat to the physical integrity of self or
others
2. The person's response involved intense fear, helplessness or horror. In children this may be
expressed instead by disorganized or agitated behavior.
• Criterion B. The traumatic event is persistently reexperienced in one (or more) of the
following ways:
1. Recurrent and intrusive distressing recollections of the event, including images, thoughts,
or perceptions. In young children, repetitive play may occur in which themes or aspects of
the trauma are expressed.
2. Recurrent distressing dreams of the event. Note: in children there may be frightening
dreams without recognizable content.
3. Acting or feeling as if the traumatic event were recurring (including a sense of reliving the
experience, illusions, hallucinations and dissociative flashback episodes, including those that
occur on wakening or when intoxicated). In young children trauma-specific reenactment may
occur.
4. Intense psychological distress and/or physiological reactivity on exposure to internal or
external cues that symbolize or resemble an aspect of the traumatic event.

Dr. Enida Xhaferi

 Diagnosis of PTSD with DSM IV criteria
• Criterion C. Persistent avoidance of stimuli associated with the trauma and numbing of general
responsiveness (not present before the trauma), as indicated by three (or more) of the following:
1. Efforts to avoid thoughts, feelings or conversations associated with the trauma
2. Efforts to avoid activities, places or people that arouse recollections of the trauma
3. Inability to recall an important aspect of the trauma
4. Markedly diminished interest in participating in significant activities
5. Feeling detached or estranged from others
6. Restricted range of effect (eg, unable to have loving feelings)
7. Sense of a foreshortened future (eg, does not expect to have a career, marriage, children, or a
normal life span)
• Criterion D. Persistent symptoms of increased arousal (not present before trauma), as indicated by
two (or more) of the following
1. Difficulty falling or staying asleep
2. Irritability or outbursts of anger
3. Difficulty concentrating
4. Hypervigilance
5. Exaggerated startle response
• Criterion E. Duration of the disturbance (symptoms in criteria B, C, and D) is more than one
month.
• Criterion F. Disturbance causes clinically significant distress or impairment in social, occupational, or
other important areas of functioning.
• Specification of duration Dr. Enida Xhaferi
 Post traumatic stress disorder
duration

• Acute – if symptoms are present for less than three

months
• Chronic – if patients display symptoms for three
months or more
• With delayed onset - symptoms appear at least six
months after the stressor

Dr. Enida Xhaferi

 Post traumatic stress disorder
management. Pharmacologic agents
• Treatment for PTSD include psychotherapies and medications.
• PTSD prevention is divided in three categories : primary
(preventing exposure); secondary (preventing symptoms
development immediately after exposure); tertiary (prevention
of PTSD worsening)
• Secondary interventions aim to target central nervous system
alterations with hydrocortizone and propranolol within weeks
after exposure for PTSD symptoms creation prevention.
• Tertiary procedures involve counseling and medication. Selective
serotonin reuptake inhibitors (SSRIs – sertraline, paroxetine) are
first-line pharmacologic agents for the treatment of PTSD.
• Other medications include include - tricyclic
antidepressants/TCAs (amytriptiline), monoamine oxidase
inhibitor/ MAOIs, anticonvulsants, benzodiazepins,
antiadrenergic agents,
• Critical incident stress management (CISM)
Dr. Enida Xhaferi
 Post traumatic stress disorder.
Psychotherapeutic interventions
• Cognitive–Behavioral Therapy (CBT)
• Exposure Therapy
• Stress Inoculation Training (SIT)
• Cognitive therapy (CT)
• Cognitive Processing Therapy (CPT)
• Eye-Movement Desensitization and Reprocessing
(EMDR)

Dr. Enida Xhaferi

 Post traumatic stress disorder and
physical disease

• A study of 3171 community responders (Spitzer C.

et al, 2009) showed that PTSD was associated with
increased risks for angina, heart failure bronchitis,
asthma, liver, and peripheral artery disease.
• Psychiatric comorbidity rates are high among
patients with PTSD and conditions include
depression, substance abuse, somatization, anxiety
and bipolar disorders.

Dr. Enida Xhaferi

Post traumatic stress disorder. CISM
• Are aimed at rescue workers, health care personnel, police
dispatchers, financial workers after robberies, people exposed
to traumatizing events, army personel and other tertiary
victims(Mitchell 1988).
• Critical incident stress debriefing (CISD)
• Pre crisis intervention programs
• Crisis intervention program (demobilization, staff
consultation and crisis management briefing
• Defusing
• CISD (introduction, fact phase, thought phase, reaction
phase, symptoms phase, teaching phase, reentry phase)
• Individual crisis prevention
• Pastoral crisis intervention
• Family CISM
• Follow up/referral
Dr. Enida Xhaferi
 Stress and autoimmune diseases
• Epidemiological evidence supporting the association
between stress related disorders and autoimmune
diseases in humans is limited.
• Existing information is largely based on male, military
sample focusing on PTSD.
• A current study of a Swedish cohort (Huan Song et
al. 2018) showed that association of PTSD, but not
other stress-related disorders, was stronger for
multiple autoimmune syndromes than for single
autoimmune disease.

Dr. Enida Xhaferi

 PTSD and autoimmune diseases
• Patients with PTSD manifest alterations in the
systems that regulate the stress response, including
the hypothalamic pituitary-adrenal (HPA) axis, and
development of a pro-inflammatory state.
• Somatic autoimmune and inflammatory diseases and
disorders have a high rate of co-morbidity with
PTSD

Dr. Enida Xhaferi

Potential mechanisms that might link
PTSD and immune dysregulations
• Reduced Circulating Cortisol
• Chronic Low Grade Inflammation. (Studies have found
that patients who develop PTSD have increased levelse of
cytokines like TNF alfa, IL-6, IL-β and perspective
association between PCR and PTSD.
• Alterations in Innate and Adaptive Immunity (alterations
of the Th1 versus Th2 cytokine balance; decrease in
number and function of peripheral Treg etc).
• Telomere shortening and premature immunosenescence

Dr. Enida Xhaferi

 Rheumatic autoimmune diseases
• Autoimmune rheumatic diseases are due to a
compromised immune response against the self.
Physicians have commonly observed that stress
adversely affects patient’s disease and many studies
have demonstrated that a high percentage of
patients have reported unusual emotional stress
before disease onset.

Dr. Enida Xhaferi

 Rheumatic autoimmune diseases

• Research among veterans showed that those

diagnosed with PTSD had higher risk for diagnosis
with an autoimmune disorder like rheumatoid
arthritis, systemic lupus erythematosus autoimmune
thyroiditis, multiple sclerosis, alone or in
combination, compared to veterans with no
psychiatric disorder (O’Donovan et al, 2014).

Dr. Enida Xhaferi

 Post traumatic stress disorder and
LES

• A large longitudinal study of 116,430 civilian

women, showed that exposure to trauma and PTSD
were associated with increased risk of SLE
occurrence (Roberts et al. 2017).
• A group of patients with fibromyalgia and PTSD
reported significantly greater levels of avoidance,
hyperarousal, anxiety, and depression than did the
patients without PTSD symptoms (Cohen et al
2002). There is overlap between fibromyalgia and
PTSD.

Dr. Enida Xhaferi

Conclusion
• Rheumatic diseases are common chronic disorders.
Several risk factors contribute to their
pathophysiology like genetic factors, sex hormones,
infections and stress. Research has showed that
psychological stress and stress-related hormones are
involved in immune modulation, which may result in
autoimmune disease. Further studies are needed to
clarify the pathophysiological implications of stress
and trauma on the onset and activity of rheumatic
autoimmune diseases and to determine whether
treatment of PTSD and lifestyle changes can decrease
the risk for developing autoimmune disorders in
affected patients

Dr. Enida Xhaferi

 References
• Brickman CM, Shoenfeld Y. The mosaic of autoimmunity. Scand J Clin Lab Invest 2001;61:3–15.

• Stojanovich L. Stress as a trigger of autoimmune disease. Abstracts book: 5th International Congress on Autoimmunity, Sorrento, Italy, vol. 355. Autoimmun Rev; 2006

• Shoenfeld Y, Isenberg D. The mosaic of autoimmunity. Research Monographs in Immunology Amsterdam. The Netherlands: Elsevier Science Publishers; 1989.

• Herrmann M, Sholmerich J, Straub RH. Stress and rheumatic disease. Rheum Dis Clin North Am 2000;26:737–63.

• Sapolsky RM, Romero ML, Munck AU. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev 2000;21:55–89.

• Donovan A., Cohen B., Seal K., Elevated risk for autoimmune disorder in Iraq and Afghanistan veterans with post-traumatic stress disorder, Biol Psychiatry. 2015 February 15; 77(4): 365–374.

• Boscarino JA. Posttraumatic stress disorder and physical illness: results from clinical and epidemiologic studies. Ann N Y Acad Sci. 2004; 1032:141–153.

• Boscarino JA, Forsberg CW, Goldberg J. A twin study of the association between PTSD symptoms and rheumatoid arthritis. Psychosom Med. 2010; 72:481–486.

• Kovacs WJ, Olsen NJ. Sexual dimorphism of RA manifestations: genes, hormones and behavior. Nat Rev Rheumatol. 2011; 7:307–310

• Zautra AJ, Parrish BP, Van Puymbroeck CM, et al. Depression history, stress, and pain in rheumatoid arthritis patients. J Behav Med 2007;30(3): 187–97.

• Brionez TF, Assassi S, Reveille JD, et al. Psychological correlates of self-reported disease activity in ankylosing spondylitis. J Rheumatol 2010;37(4): 829–34.

• Vandvik IH, Hoyeraal HM, Fagertun H. Chronic family difficulties and stressful life events in recent onset juvenile arthritis. J Rheumatol 1989;16(8):1088–92.

• Pawlak CR, Witte T, Heiken H, et al. Flares in patients with systemic lupus erythematosus are associated with daily psychological stress. Psychother Psychosom 2003;72(3):159–65.

• Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet 2001;358(9285):903–11.

• O’Dell JR. Therapeutic strategies for rheumatoid arthritis. N Engl J Med 2004; 350(25):2591–602.

• Halliday JL. Psychological aspects of rheumatoid arthritis. Proc R Soc Med 1942;35(7):455–7.

• Robinson CE. Emotional factors and rheumatoid arthritis. Can Med Assoc J 1957;77(4):344–5.

• Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, DC: American Psychiatric Association, 1994.

• Xhaferi E. Lamaj F. An Overview of Systemic Sclerosis, Intern Journal of Science and Research. 2016, 5 (11). 1050-1062.

• Xhaferi E. Backa T, et al Lupusi Eritematoz sistemik manifestimet me te shpesht klinike dhe diagnoza, Mjek Bashkekohore .17/2016, 135-144.

• Rothbaum BO, Foa EB, Murdock T, et al. A prospective examination of post-traumatic stress disorder in rape victims. J Traumatic Stress 1992;5(3):455–75.

• Brewin CR, Andrews B, Valentine JD. Meta-analysis of risk factors for posttraumatic stress disorder in trauma-exposed adults. J Consult Clin Psychol 2000;68(5):748–66.

• Yehuda R. Neuroendocrinology of trauma and posttraumatic stress disorder. In: Yehuda R (ed). Psychological Trauma Washington, DC: American Psychiatric Press, 1998:97–131

• Resnick HS, Kilpatrick DG, Dansky, et al. Prevalence of civilian trauma and posttraumatic stress disorder in a representative national sample of women. J Consult Clin Psychol 1993;61(6):984–91.

• Xhaferi E., Backa Cico T., et al Ocular involvement in ankylosing spondylitis, Intern. Journ of ecosystems and ecology science. IJEES, Vol5,no.3, 2015, 393-398.

• Xhaferi E, Lamaj F. Current insights into the pathogenesis of rheumatoid arthritis. Intern Journal of Science and Research 2015. 4 (10), 1442-1450.

• Harbuz M. , Richards, L. , CHover-Gonzalez, A. , Marti-Sistac, O. and Jessop, D. (2006), Stress in Autoimmune Disease Models. Annals of the New York Academy of Sciences, 1069: 51-61. doi:10.1196/annals.1351.005.

• Cutolo M., Straub R.H., Stress as a Risk Factor in the Pathogenesis of Rheumatoid Arthritis Neuroimmunomodulation 2006;13:277–282.

• Cohen H., Neumann L., Haiman Y., et al., Prevalence of Post-Traumatic Stress Disorder in Fibromyalgia Patients: Overlapping Syndromes or Post-Traumatic Fibromyalgia Syndrome? Seminars in Arthritis and Rheumatism, Vol 32, No 1 (August), 2002: pp 38-50.

• Hassett A., Clauw D., The role of stress in rheumatic diseases Arthritis Research & Therapy 2010, 12:123.

• Xhaferi E., Backa Cico T., et al Cardiac manifestations in ankylosing spondylitis, Intern. Journ of ecosystems and ecology science IJEES, Vol5, no.3, 2015, 441-446.

• Xhaferi E. Backa T. Idiopathic Inflammatory Myopathies: A Case of a Woman with Antisynthetase Syndrome, Intern Journal of Science and Research 2015, 4 (11), 1878-1884.

• Roberts, A. L., Malspeis, S. , Kubzansky, et al., (2017), Association of Trauma and Posttraumatic Stress Disorder With Incident Systemic Lupus Erythematosus in a Longitudinal Cohort of Women. Arthritis Rheumatol, 69: 2162-2169.

• Benros M., Posttraumatic Stress Disorder and Autoimmune Diseases, Biological Psychiatry February 15, 2015; 77:312–313.

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Dr. Enida Xhaferi
Roberts, A. L., Malspeis, S. , Kubzansky, L. D., et al., (2017), Association of Trauma and Posttraumatic Stress Disorder With Incident Systemic Lupus Erythematosus in a Longitudinal Cohort of Women. Arthritis Rheumatol, 69: 2162-2169.
Dr. Enida Xhaferi