What is the Diagnostic Criteria for PANDAS?

Patient Presentation
A 10-year-old male came to clinic with personality changes.
About three weeks ago, he had a sore throat, fever and then after a few days began acting differently.
Initially he made some odd comments that the family noticed and was moodier.
His teacher noticed him asking to wash his hands frequently. She inquired and he said that he didn’t want to eat or drink at school.
When the teacher persisted, he said that the food and water was poisoned.
The teacher contacted his mother. When his mother questioned him, he said that he didn’t know where the food or water came from or who had cooked it at school.
His mother asked him about how he felt about the food and water at home and he said that he wasn’t worried much but that he still had to be careful.
The mother also noticed that he seemed to be washing his hands more at home too.
His mother stated that he seemed to be preoccupied with making sure his homework was done and was in his bag to go to school the next day.
His teacher reported that the quality of his work was unchanged; but he seemed to be having problems concentrating and was working harder and longer to produce the same work.
In the office, he stated that he just felt better after washing his hands and that he wanted to make sure his homework was done.
He denied any other obsessive or compulsive behaviors or thoughts.
Mother and patient said he was functioning otherwise well.
The past medical history showed a boy who was described as “sensitive” but not a worrier. He had some viral-induced bronchospasm as a preschooler.
The family history was negative for any neurological or psychiatric illnesses except for an aunt with post-partum depression and a paternal cousin with attention deficit disorder.
Older family members had coronary artery disease or strokes.
The review of systems was negative including fevers, weight changes, sweating, and chills.
He also denied any visual or auditory hallucinations, tics, orchoreiform movements. He was having problems sleeping.
The pertinent physical exam showed a healthy appearing boy with growth parameters around 25%. He was afebrile with normal pulse and blood pressure.
He easily answered questions with a normal speech rate and content.
He was clean and dressed appropriately.
Skin examination showed some general dry skin on his upper arms, but no rashes and no nailbed abnormalities.
HEENT examination was normal except for minor clear rhinorrhea. His pharynx had no erythema, exudates or ulcers.
Heart examination was normal with no murmur and good pulses.
Neurological examination was normal.
He was Tanner stage 1.
A short mental status examination revealed him to be oriented to time, place, person and situation.
The laboratory evaluation included a rapid strep test and throat culture that were negative. Complete blood count and thyroid function tests were normal.
Anti-streptolysin O titers came back the following day at 494 IU/ml (normal = 0-240 IU/ml).
A diagnosis of possible PANDAS was made. The mother and physician decided to treat with a 10-day course of cefadroxil. Additionally he was referred for psychological counseling.
At the 3 week follow-up, the patient’s clinical course had improved. He had no concerns about his homework, was washing his hands an appropriate amount and didn’t feel compelled to do so.
He still had some worries about the food and water at school but was willing to eat at school if the items were brought from home.
His mother and he were happy with the progress and were going to continue with the cognitive behavioral therapy, with another follow up appointment was scheduled at 6 weeks.

Discussion
PANDAS is an acronym which stands for pediatric autoimmune neuropsychiatric disease associated with streptococcal disease.
It was first described in 1998. The exact pathophysiology is not known but various evidence supports an autoimmune mediated mechanism.
The proposed mechanism is that streptococcal infection produces antibodies that are capable of cross-reacting with specific areas of the brain such as the basal ganglia and then produces behavioral and neuropsychiatric symptoms.

Current treatment is controversial because of lack of research studies. Antibiotic treatment for evidence of current streptococcal infection is usually given. Prophylactic antibiotic treatment is not recommended.
Neuropsychiatric drugs are used for treatment of disabling tics and/or OCD in addition to cognitive behavioral therapy. Immunomodulation therapy such as plasmapheresis is recommended to be reserved for patients participating in research protocols.

Learning Point
Diagnostic criteria for PANDAS is:

  • Age – 3 years to puberty
  • Tics or obsessive-compulsive disorder (OCD) – based on DSM-IV criteria
  • Episodic or up and down course of symptom severity – sudden onset of symptoms with slow gradual resolution over weeks or months, episodes may recur after another streptococcal infection
  • Streptococcal infection – evidence of temporally related infection. Such evidence could include a positive throat culture, ASO titers peaking at 3-6 weeks, or anti-DNAse peaking after 6-8 weeks.
    Concurrent associated neuropsychiatric symptoms – especially hyperactivity, choreiform movements or tics. Other problems can include: learning problems, depression, anxiety, mood swings, sleep problems, fine or gross motor impairment such as writing problems.

This patient met most of the criteria for PANDAS: he was the proper age, had OCD, had sudden onset of symptoms with slow resolution, had temporal evidence of streptococcal infection and some neuropsychiatric symptoms. However, he did not have hyperactivity, choreiform movements or tics specifically.

Questions for Further Discussion
1. What medical evaluation should be done for patients with acute psychiatric symptoms?
2. What other psychiatric diseases may be associated with an immunological etiology?
3. Is PANDAS associated with development of other psychiatric diseases in the long term?
4. What is the relationship of PANDAS to Sydenham’s chorea?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Information prescriptions for patients can be found at MedlinePlus for these topics: Streptococcal Infections, Obsessive Compulsive Disorder and Movement Disorders

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

Kurlan R, Kaplan EL,
The Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infection (PANDAS) Etiology for Tics and Obsessive-Compulsive Symptoms: Hypothesis or Entity? Practical Considerations for the Clinician
Pediatrics. 2004;113;883-886.

Murphy TK, Sajid MW, Goodman WK.

Immunology of obsessive-compulsive disorder.
Psychiatr Clin North Am. 2006 Jun;29(2):445-69.

de Oliveira SK.

PANDAS: a new disease?
J Pediatr. 2007 May-Jun;83(3):201-8.

da Rocha FF, Correa H, Teixeira AL.
Obsessive-compulsive disorder and immunology: A review.
Prog Neuropsychopharmacol Biol Psychiatry. 2008 .

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

  • Interpersonal and Communication Skills
    17. A therapeutic and ethically sound relationship with patients is created and sustained.

  • Systems Based Practice
    25. Quality patient care and assisting patients in dealing with system complexities is advocated.

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

    Date
    May 27, 2008

  • What is Köhler's Disease?

    Patient Presentation
    An 11-year-old male came to orthopaedic clinic with a history of injuring his right ankle 2 years ago in a soccer game.
    He thinks he may have twisted it but is unsure. The injury didn’t appear significant and he was not evaluated.
    Since then he has had intermittent right ankle pain after mild trauma (i.e. sliding into a base during baseball) or high activity levels.
    The pain is always in the same location and sometimes there is mild swelling.
    It has not stopped him from playing sports, he has not taken any medication and is able to walk without problems during the pain.
    The family history, past medical history and review of systems was negative.
    The social history reveals a boy who is doing well in school and participates on many athletic teams.
    The pertinent physical exam showed a male with 75-90% growth parameters and who was well appearing.
    His musculoskeletal examination revealed mild pain with dorsiflexion and inversion of the right ankle. There was pain over the navicular bone medially. The rest of his examination was normal.
    Review of his locally obtained radiographs revealed an irregular ossification of the navicular bone consistent with the diagnosis of Köhler’s disease or osteochondrosis of the tarsal navicular bone.
    The patient was allowded to continue his activities and a shoe insert was prescribed to provide more cushioning and distribution of the forces on the foot.
    He was to return in 6 months for re-evaluation. If there was worsening symptoms or signs of disease, a computed tomograph examination would be ordered to evaluate for possible bone fragments or other problems that would need surgical correction.

    Discussion
    Osteochondroses are pathological changes in a bone growth center that are caused by ischemic necrosis or traction.
    The causes are not well known but vascular accidents, coagulation and genetics are implicated.
    Two common osteochondroses are Osgood-Schlatter disease or apophysitis of the tibial tubercle, and Legg-Calvé-Perthes caused by ischemic necrosis of the capital femoral epiphysis and others.

    About 40 osteochondroses are eponymously named: Osgood (American) and Schlatter (Swiss) who described this disease almost simultaneously in 1903.
    Similarly, Legg (American), Calvé (French) and Perthes (Germany) described their osteochondrosis separately but almost simultaneously in 1908.
    Interestingly Waldenström (Swedish) also described the disease during the same time period but his name is not as consistently associated with the disease.
    Alban Köhler was a German radiologist. His name is also associated with Freiberg (American) to describe osteochondrosis of other foot bones.

    Learning Point
    Köhler’s disease is more common in boys than girls, and occurs most often in 5-10 year olds. Exact cause is unknown but there is disruption of vascular supply to the bone which then causes necrosis; later revascularization causes reformation of the bone.
    Patients can present with an antalgic limp and point tenderness of the navicular medially. Generally, children can walk and there may be soft tissue swelling or redness.
    Radiographs show irregular ossification of the navicular bone.

    Treatment is usually just monitoring. Patients generally may ambulate but sometimes casting for 6-8 weeks is recommended. Usually patients are better in 3-6 months but some may have a delay in healing. Most patients do not have any complications.

    Questions for Further Discussion
    1. What should be considered in the differential diagnosis of chronic foot pain?
    2. When should a patient be referred to an orthopaedist?
    3. When should a patient be referred to a podiatrist?

    Related Cases

      Symptom/Presentation

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Information prescriptions for patients can be found at MedlinePlus for these topics: Osteonecrosis and Foot Injuries and Disorders.

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    Mier, RJ, Brower TD. Pedatric Orthopedics. A Guide for Primary Care Physicians. Plenum Medical Book Company, New York. 1994;39-47.

    Vargas-Barreto B, Clayer M. Köhler’s Disease. eMedicine. Available from the Internet at http://www.emedicine.com/orthoped/TOPIC410.HTM (rev. 9/18/2007, cited 4/7/2008).

    Alban Köhler. Who Named It.
    Available from the Internet at http://www.whonamedit.com/doctor.cfm/2302.html (rev. 2008, cited 4/7/08).

    Calvé-Legg-Perthes disease. Who Named It.
    Available from the Internet at
    http://www.whonamedit.com/synd.cfm/908.html
    (rev. 2008, cited 4/7/08).

    Köhler Disease I. Who Named It.
    Available from the Internet at http://www.whonamedit.com/synd.cfm/2676.html (rev. 2008, cited 4/7/08).

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    8. Health care services aimed at preventing health problems or maintaining health are provided.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

    Date
    May 19, 2008

  • How Do You Treat Chronic Urticaria?

    Patient Presentation
    A 21-year-old female came to clinic in the afternoon with a 5-6 week history of hives.
    She initially noticed herself itching in the later evening especially on her trunk. She didn’t really notice any reason for the itching nor any skin that was reddened or discolored.
    She had difficulty falling asleep because of the itching.
    Over the next few days she noticed that the itching recurred but now it also was on her feet and around her waistband in the evening.
    Over the next few weeks, she had increasing itching that now would occur in the afternoon and evening and involved her feet, especially the soles and between her toes, around her waistband, shirt wristband, flexural area of elbows, and was especially pronounced where she wore her bra.
    She also noticed in the morning that she would have some itching of the back of her head and buttocks, but not other areas. Once the afternoon or evening episodes began, they did not stop until she was sleeping.
    The morning episodes would occur after wakening and stop sometime after she was in school.
    She stated that reddened areas of her skin with central white papular areas occurred. These areas came and went.
    The pruritus did not stop her from her activities but was very annoying and socially embarrassing at times. She tried diphenhydramine with little or no relief.
    She denied any new lotions, soaps, shampoos, detergents, makeup, or perfume. She had not had any new intense light exposure.
    She denied any medications or recent illness including upper respiratory tract diseases. She said she had no problems eating, drinking or breathing.
    The past medical history showed a healthy female with otitis media as a young child. She did not have a history of allergies or skin problems.
    The family history was positive for a maternal aunt with hyperthyroid disease.
    The review of systems was otherwise negative.
    The pertinent physical exam showed a healthy female with normal growth parameters.
    Her skin examination showed fine urticarial lesions on her soles, trunk along her bra (especially under the breasts), and abdomen around the waistband.
    She had no excoriations of the skin. Stroking the skin with the top of a pen did not elicit a wheal and flare reaction.
    She had some freckling on her face, upper arms, upper legs and shoulders. Several freckles were stroked and did not elicit a wheal and flare reaction either.
    The diagnosis of a physical urticaria was made most likely a pressure urticaria. The work-up included doing thyroid function and thyroid autoantibody testing because of the family history and possibility of asymptomatic thyroid disease being the inciting cause. The testing was negative.
    The patient’s clinical course over the next 2-3 weeks improved after taking over-the-counter loratadine daily.

    Discussion
    Chronic urticaria is defined as wheals that occur at least twice weekly for more than 6 weeks. Because this is broad, some people add that the wheals must be present for more than 1 hour (which distinguishes chronic urticaria from dermatographism) and less than 24-36 hours (which distinguishes it from urticaria-vasculitis).
    The lesions can be ‘just’ irritating or very painful and even indurated. Outbreaks can occur for weeks-years and affects up to 3 % of the population. Generally there are no systemic problems but some patients have greatly diminished quality of life that is equivalent to people with severe coronary artery disease.
    Chronic urticaria can be caused by a specific physical stimulus or often is idiopathic. Up to 1/3 of idiopathic cases appear to be autoimmune related, particularly associated with antithyroid antibodies which may cause overt or subclinical hypothyroidism.

    Pressure urticaria is one of the physical urticarias (others being caused by exercise, heat, cold, water exposure, sun exposure, and dermatographia). It is more common in men than women and occurs most often in 20-30 year olds (range 5-63 years).
    Usually the wheals occur 30 minutes – 6 hours after the pressure and last 8 hours to 3 days. The pressure can be caused by walking, standing, sitting, carrying a handbag or groceries, using a hammer, sexual intercourse or many other activities.
    Many people with pressure urticaria also have chronic urticaria. A dermographometer may be used for a pressure challenge testing to help make the diagnosis.

    Learning Point
    Treatment for chronic urticarias is with second-generation H1 antihistamines (e.g. loratadine, desloratadine, fexofenadine, etc.). Physical urticarias tend to respond reasonably well to second-generation H1 antihistamines. (Solar urticaria doesn’t respond as well though.)
    For those that are not responding well, a combination of second-generation H1 antihistamines and H2 antihistamines (e.g. cimetidine, ranitidine, etc.), or second-generation H1 antihistamine with montelukast can be effective.
    Some patients require a combination of H2 antihistamines or even systemic steroids to control their symptoms.

    Questions for Further Discussion
    1. What are the indications for referral to dermatology?
    2. How is acute urticaria treated?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Information prescriptions for patients can be found at MedlinePlus for these topics: Hives and Itching
    and at Pediatric Common Questions, Quick Answers for this topic: Hives

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    Sciacca-Kirby J, Kim E, Levin RM, Heymann WR, Pressure Urticaria. eMedicine.
    Available from the Internet at http://www.emedicine.com/derm/topic447.htm (rev. 10/2/06, cited 3/31/08).

    Inettis E, Colanardi MC, Soccio AL, Ferrannini A, Vacca A.
    Desloratadine in combination with montelukast suppresses the dermographometer challenge test papule, and is effective in the treatment of delayed pressure urticaria: a randomized, double-blind, placebo-controlled study.
    Br J Dermatol. 2006 Dec;155(6):1279-82.

    Jauregui I, Ferrer M, Montoro J, Davila I, Bartra J, del Cuvillo A, Mullol J, Sastre J, Valero A.
    Antihistamines in the treatment of chronic urticaria.
    J Investig Allergol Clin Immunol. 2007;17 Suppl 2:41-52.

    Huang S, Connelly KP, Windle ML, Schwartz RA, Poth MP, Jyonouchi H. Urticaria. eMedicine.
    Available from the Internet at http://www.emedicine.com/ped/TOPIC2373.HTM (rev. 9/21/2007, cited 3/31/08).

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    8. Health care services aimed at preventing health problems or maintaining health are provided.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

    Date
    May 12, 2008