PANDAS PITAND

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PANDAS & PITAND Syndromes

Among the important scientific developments that have come out of the nineties, Paul Ewald's (Amherst College, Mass) evolutionary research deserves particular attention. By reinterpreting well known evolutionary theories, that somehow got "twisted" over the past century, Ewald has offered us a new prospective on the role of infectious agents in common diseases of modern man. A mere possibility that an infection can indeed be one of the major causes of diseases such as heart disease, atherosclerosis, mental illness, and cancer is very exciting and if his speculations are confirmed, new treatment opportunities will emerge soon.

Do you wish to learn more about the subjects from this page, or to learn more about the future path of medical sciences? Find it at our Reference page.

Controversial and still highly contentious concepts of PANDAS (Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococci) and PITAND (Paediatric Infection-triggered Autoimmune Neuropsychiatric Disorders) were introduced by A. J. Allen and Swedo et al. in the late nineties. The premise brought forward by these researchers, that certain mental illnesses (e.g. Obsessive-compulsive disorder, tic disorders including Tourette's syndrome) can be directly caused by an infection with a common infectious agent (PANDAS: Group A beta-hemolytic Streptococcus - GABHS) or be a result of an auto-immune reaction following the infection with some other common infectious agents (PITAND: viruses, Mycoplasma, etc.), severely challenges a century of Freudian "devotion" of the medical community. In a simple language, theories of Allen and Swedo are bringing the mental illness back to its biological roots and essentially define it as a physical illness with mental symptoms. Recent scientific evidences are widening the list of possible mental illnesses that could be included into PANDAS and PITAND group. Certain cases of Anorexia nervosa (see the footnote below), psychotic symptoms following the Lyme disease and at least some cases of Autistic Spectrum Disorders have all been linked to an infectious agent and their pathophysiology appears compatible with PANDAS and PITAND syndromes.

Sokol et al. (1997) reported a group of patients diagnosed with Anorexia nervosa who were classified as PANDAS. Our experiences bring to light new information on this particular group:

There is a fundamental difference in presenting clinical symptoms between patients suffering from a "classic" Anorexia nervosa and patients in whom the diagnosis of PANDAS is suspected.

In so-called "classic" anorexia, patients' main (and the most common) complaint is a pervasive distortion of (their own) body image. In patients with PANDAS who present with anorexia however, frequently elicited complaint is an overwhelming obsession with (fear of) chocking on food.

If you would like to learn more about PANDAS and PITAND syndromes, review PANDAS clinical cases page.

Modified criteria (after A. J. Allen) necessary for the diagnosis of PANDAS and PITAND syndromes are listed in the table below. While the prerequisite of a proven GABHS (Group A beta-hemolytic Streptococcus) infection makes the diagnosis of PANDAS scientifically sound, somewhat murkier criteria have been established for PITAND syndrome(s).

PANDAS diagnostic criteria

(1) Current or past presence of symptoms (DSM IV) of Obsessive Compulsive Disorder, Tic Disorder (including Tourette's), Anxiety disorder (especially Separation anxiety disorder) Anorexia nervosa subgroup (please, see the footnote above!). Autism or Autistic Spectrum Disorder, particularly Asperger's syndrome* can be associated with PANDAS syndrome.

(2) Symptom onset between 18 months of age and puberty.**

(3) Episodic course of symptom severity ("wax-and-wane pattern") characterized by the abrupt onset of symptoms and/or frequent, dramatic symptoms exacerbation followed by slow and prolonged improvement.

(4) Symptom exacerbation associated with beta-haemolytic Streptococcus Group A infection.***

(5) Presence of an abnormal neuropsychiatric examination, including marked motor hyperactivity, adventitious movements, tics, mydriasis, noticable deterioration in fine motor skills (i.e., writing and drawing), decrease in patient's intellectual performance (i.e., marked decrease in math skills), etc.

(6) Measurable clinical improvement following the administration of a "Steroid Burst".

DISQUALIFYING FACTORS (absolute): Presence of symptoms before 1 year of age.

* On the basis of recent clinical experiences, development of PANDAS in patients with Asperger's may be more common than previously known.

** Onset of puberty as the upper age limit for the appearance of PANDAS may be artificially imposed and may not necessarily be true.

*** There may be at least TWO clinical reports on patients presenting with classic PANDAS symptoms, who tested negative on GABHS, but positive on Mycoplasma pneumonie. It has been our experience that the symptom recurrence can be induced by mere exposure to GABS with no clinical nor laboratory data confirming the infection.

PITAND diagnostic criteria

(1) At some time in his or her life, the patient must have met diagnostic criteria (DSM IV) for one of the following neuropsychiatric disorders: Obsessive Compulsive Disorder, Tic Disorder (including Tourette's). Inclusion of certain individual cases of Autism (or Autistic Spectrum Disorder) is possible.

(2) Pediatric onset: symptoms of the disorder first become evident between 18 months of age and the beginning of puberty.

(3) The onset of clinically significant symptoms must be sudden (with or without a sub clinical prodrome), and/or there must be a pattern of sudden, recurrent, clinically significant symptom exacerbation and remissions ("wax and waning pattern"). Onset of a specific episode typically can be assigned to a particular day or week, at which time symptoms seem to "explode" in severity, and they are frequently associated with an infectious episode.

(4) There must be evidence of an antecedent or concomitant infection. Such evidence might include a positive throat culture, positive streptococcal serologic findings (e.g. anti-streptolysin O or anti-streptococcal DNAse B), or a history of illness (e.g. pharyngitis, sinusitis, infection with Epstein-Barr virus, influenza, ?recurrent otitis media), and possibly recent exposure to childhood vaccination.

(5) Presence of auto antibodies (anticardiolipin, antineuronal, antibody/antigen complexes, etc.)

(6) During the exacerbation, the majority of patients will have an abnormal neuropsychiatric examination, frequently with hyperactivity and adventitious movements ("choreiform" movements).

(7) Measurable clinical improvement following the "Steroid Burst".

Modified "Allen criteria" (from Albert J. Allen Group A Streptococcal Infections and Childhood Neuropsychiatric Disorders CNS Drugs Oct. 1997 8(4) 267-275

So, What is This All About?

The most exciting prospect of PANDAS and PITAND theory is realization that a biological agent(s) (in this case, an infectious microorganism) has been identified as a single cause of a mental illness. PANDAS and (possibly) PITAND do indeed represent a disease(s) that satisfies the McGovern and Troisi criteria (please refer to Autism page). Various descriptive terms so much abused in current scientific terminology of mental illnesses ("chemical imbalance", "abnormal brain chemistry", etc.) that have absolutely no scientific meaning nor diagnostic or therapeutic value, might be finally relegated to history. It is likely that following a century of unsuccessful search for the disease of the mind, the body will be where the answers shall be found.

Once the cause of an illness (in this case a mental illness) has been identified, search for an adequate treatment is the next logical step. In PANDAS and PITAND syndromes an adequate treatment already exists and has been proven successful. Use of antibiotics for GABHS infection (i.e. Penicillin) does not only "control" the symptoms but, in certain cases, may cure the patient. Once however, the damage to the nervous system has been demonstrated (both in PANDAS and PITAND) further treatments modalities may be necessary, and these are readily available as well (corticosteroids, Intravenous immunoglobulin, anti-inflammatory compounds other than steroids, etc.). It is also extremely important to mention that the resulting damage to the nervous system symptomatic of PANDAS and PITAND syndromes can be reversed in its early stages (please refer to our Bibliography page), and a complete cure can be expected. It is likely that with the passage of time and an increased acceptance of Allen's and Swedo's theories, a definite cause of a number of mental illnesses overwhelming the modern society will be defined and (possibly) true cures achieved.

Review of currently available treatments for PANDAS

Antibiotics

Antibiotics have been the mainstay of PANDAS treatment (together with SSRIs). The idea behind use of antibiotics is the eradication of Group A beta hemolytic Streptococcus. Unfortunately, the results have been mixed at best what corresponds to our professional experiences with PANDAS patients as well. We have seen severely symptomatic patients who have had negative antibody tests for Strept and at the same we have seen at least one patient whose symptoms have disappeared completely following the antibiotic treatment despite of persistence of high Strept antibody titers. It is possible and even likely that use of antibiotics in the early stages of PANDAS can result in a complete recovery. It has been our experience however, that patients with pronounced behavioral symptoms (severe separation anxiety, i.e.) are less likely to relinquish all of their symptoms following the use of antibiotics.

Corticosteroids

Just the fact that the "steroid burst" (used to test possible future effectiveness of IVIG) tend to control PANDAS symptoms effectively brings it into consideration as a possible treatment for PANDAS. Since the short-term steroid treatment only controls the symptoms temporarily and the prolonged use of it may have rather serious side effects, corticosteroids have not been (and should not be) used as a treatment in PANDAS.

Removal of adenoids and tonsils

At least one recent study reports symptom resolution in patients with PANDAS following a surgical removal of tonsils and/or adenoids. Since the fore said study had only limited time follow-up of these patients, the success (and the future failure) of this treatment is likely to parallel the results of antibiotic treatment(s).

Selective serotonin reuptake inhibitors (SSRIs)

SSRIs (i.e. Lexapro, Prozac, Luvox, Paxil, Zoloft) have been frequently and rather generously prescribed to children with PANDAS syndrome. Few parents understand that the use of these medications in children and particularly for symptoms of PANDAS is not recommended in manufacturers' brochures and is considered "off label" use. In addition, possible (sometimes very serious) side effects have recently prompted FDA to require so-called "black box" warning to be displayed on the packaging of these medications. Considering the fact, that clinical benefits of SSRIs have not been proven in patients with PANDAS, and the fact that these medications can have serious side effects, their frequent and prolonged use in PANDAS should be seriously questioned.

Plasmapheresis

There are no true studies performed and/or reported on use of plasmapheresis in patients with PANDAS. There are however multiple case reports in the literature and the success rate of this treatment appears to be rather high. Unfortunately, relatively high incidence of (sometimes) serious side effects makes this therapeutic venue an unlikely treatment choice in PANDAS. Taking this into consideration and the fact that the effectiveness of this treatment equals the results of IVIG treatment, in our opinion plasmapheresis should not be a first choice of treatment for PANDAS.

IVIG

In a carefully selected group of patients the effectiveness of the IVIG treatment in PANDAS patients appears excellent. It has been our experience that a complete and lasting recovery can and should be expected within days or weeks following the treatment (please check PANDAS clinical cases page) in almost all patients. This, relatively safe procedure can be done in an outpatient setting thus avoiding additional trauma to the child and his/her parents. Unfortunately the serious drawback to this treatment is its cost and the fact that many insurance companies have not covered it until now. Recently however, several insurance carriers have started to cover the cost of the infusion. If you wish to learn more about this treatment please refer to our IVIG page!

You can review samples of PANDAS clinical cases seen and treated in our offices and learn tips on how to recognize signs and symptoms of PANDAS!

If you feel that your chid may have PANDAS, e-mail us your questions. Dr. Kovacevic will reply promptly.