Autism and Adult Psychiatry

October 31, 2012
William M. Bolman, MD

I.  Why do I need to know about Autism?
    1)  Because of the continuing increase in prevalence.  In the last 25 years the prevalence has climbed from 2 per 1,000 to 1 in 54 boys and continues to rise.
    2)  For the past 15 years I have had an autism practice and most of these young people are headed towards adulthood and their parents will be calling you mostly for medication support.
    3)  Many persons with autism also have co-morbid psychiatric conditions that are often responsive to medication.  The most common are anxiety, depression, mood dyscontrol.  A few have psychotic symptoms.  Mostly their medication needs will be stable and continued from late adolescence.

II.  If I see patients with autism, what do I need to know?
    1)  Psychopharmacology.
    2)  How to work with families in general problem-solving.  
    Really, I’m not kidding, most of the technical stuff will have been taken care of during childhood.  At this time the issue is simply maintenance and some general support.  Any continuing problems and you will contact the Autism Society of Hawaii (I’m the president, and if I can’t help I have a very smart Professional Advisory Board.  You can reach me at [email protected]  If you have autistic patients/families and think you need a consult, let me know.  I still see patients for evaluations but not for ongoing psychopharm treatment.

III.  Other than that, I hope most of you know that neuroscience is experiencing an absolutely thrilling period of growth due to technological improvements in neuroimaging and the fields of epigenetics, and systems neurobiology that is beginning to impact psychiatry.  Regarding neuroscience, it is now possible to label a single neuron or group of similar neurons with an optical tracer (a protein that illuminates when exposed to light).  That means one can start tracing brain circuitry.  We have learned that for neurodevelopmental conditions like autism the pathology is not necessarily in the neuron.  Rather it’s in the neuronal support system – astrocytes, oligodendrocyes, and the extracellular matrix including cytokines from the immune system.  In particular, the development and function of the synapse and interneurons is affected.  In epigenetics it is now known that what we were previously told was ‘junk DNA’ actually controls the standard genes in neuronal development and response to the environment.  We know that the reason the autism spectrum conditions affect each individual in different ways and with different severity (the phenotype) is because there is a very large set of genes that interact in multiple ways (genetic pleiotropy – check it out on Wikipedia).  However there are some common molecular pathways such as redox homeostasis (oxidation-reduction cell balance) that may be affected by medications and gene transfer.
    There are a few really interesting insights from all this research.
    1)  Autism, schizophrenia, bipolar disorder, ADHD, learning disabilities and probably intellectual disability (the polite term for MR) share many of the same genes.  
    2)  Some of these conditions, especially autism, improve considerably with early environmental support (“Applied Behavior Analysis”).  It has also been shown in several instances that gene replacement (mostly in mouse models of neurodevelopmental conditions) in adulthood can totally reverse the neuropathology!!!   The implication is that many of these conditions do not represent irreversible brain damage – they represent homeostatic imbalance as cells and neural systems try to adapt to the molecular imbalances.
    3)  Autism (and related conditions) are not merely neurologic conditions.  The immune systems of innate and adaptive immunity are hugely involved due to their joint embryological origin from primal ectoderm.  

SO, stay tuned!   Go into the National Library of Medicine’s website (PubMed), become a member (free), type in “Molecular Neurobiology AND Autism” and enjoy some stuff that did not exist when we were in medical school!

The reason I’m so turned on by all this stuff is because I’m so old that as a young pediatrician I used to treat polio and leukemia, both conditions solved by genetic, immunologic and neuroscientific research, and we are on the same path.

Cutaneous Drug Reactions and Psychiatric Medications

September 19, 2012
Miki Shirakawa Garcia MD | Dermatology | Queens Hospital POB II

One of the most common manifestations of a drug reaction is a cutaneous eruption. If a drug reaction is suspected, the type of rash should be characterized and the onset in relation to the patient’s medications should be evaluated. There are some medications that are more commonly associated with specific types of eruptions.  If the possible offending medication is not a commonly associated medication, a literature search in Medline or in a drug database (Drug Alert Registry or Medwatch) can be helpful. Patients have a higher risk for a drug reaction if they are female, elderly, African American, immunosuppressed, take multiple medications, or have serious illnesses. The goal of this article is to provide a brief summary of cutaneous drug eruptions that are pertinent to medications commonly used in psychiatric patients.

Exanthematous or morbiliform drug eruptions present with symmetric erythematous macules on the trunk and upper extremities that progressively becomes confluent and palpable, sometimes urticarial or scarlatiniform (Figure 1). There is no mucous membrane involvement.  The rash may be accompanied by a low-grade fever and/or pruritus.  Exanthematous eruptions are most commonly seen four to fourteen days after starting the medication and most commonly secondary to antibiotics (aminopenicillins, sulfonamides, cephalosporins), anticonvulsants and allopurinol. After discontinuation of the offending medication, the rash will resolve on its own within one to two weeks.  Topical corticosteroids can be used to treat the pruritus.

Drug reaction with eosinophilia and systemic symptoms (DRESS) can be life-threatening due to possible internal organ failure.  Onset is usually two to six weeks after starting the medication and most commonly seen with anticonvulsants, antibiotics (sulfonamides, minocycline) and allopurinol. Clinically, DRESS manifests with a fever and a morbiliform eruption that starts on the face, trunk and upper extremities. Edema of the face is common. Patients will have prominent eosinophilia and liver enzymes should be monitored for possible fulminant hepatitis.  The cutaneous and systemic symptoms may last weeks to months after drug withdrawal. Treatment of DRESS requires corticosteroids, which should be systemic if there is internal organ involvement.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but potentially fatal drug reactions. SJS or TEN can start an average of one to three weeks after starting the medication. SJS and TEN are characterized by fever and painful mucocutaneous lesions that can be a dusky erythema or flat atypical targets.  The lesions usually start on the trunk and spread to the head/neck and proximal upper extremities.  This is followed by desquamation within hours to several days after onset. SJS involves less than 10% of body surface area and TEN involves greater than 30% of body surface area. Mortality rate is 1-5% for SJS and 25-35% for TEN. Most commonly implicated medications are sulfonamides, anticonvulsants, NSAIDs, and allopurinol. Specific to psychiatry, the most common offending medications are amithiozone, barbiturates, carbamazepine, chlormezanone, phenytoin, lamotrigine, and phenylbutazone. It is important that treatment is instituted in a closely monitored unit such as a burn unit with supportive care, wound care, and possible IVIG.

Some medications can cause a phototoxic or photoallergic reaction. Phenothiazines, in addition to tetracyclines, NSAIDs, and fluoroquinolones, can cause a phototoxic skin eruption. Phototoxic eruptions are characterized by an exaggerated sunburn appearance in the photodistributed areas, followed by hyperpigmentation. Photo-onycholysis and pseudoporphyria can also be seen in phototoxic reactions. Common medications to cause a photoallergy include phenothiazines, tricyclic antidepressants, thiazide diuretics, sulfonamide antibiotics, sulfonylureas, quinine or quinidine, NSAIDs and antimalarials.  Photoallergic reactions are usually more chronic and appear as a pruritic dermatitis or lichen planus-like eruption in sun-distributed locations.

Other uncommon drug reactions associated with medications used in psychiatry include fixed drug eruptions, linear IgA bullous dermatosis, pseudolymphoma and drug-induced psoriasis.  Fixed drug eruptions recur in the same location and can be secondary to sulfonamides, NSAIDs, barbiturates, tetracyclines and carbamazepine. Linear IgA bullous dermatosis is associated with vancomycin, β-lactam antibiotics, captopril, NSAIDs, phenytoin, rifampin, sulfonamides, amiodarone, furosemide, lithium and G-CSF. Pseudolymphoma can occur with anticonvulsants (phenobarbital, carbamazepine), antipsychotics (chlorpromazine, promethazine), imatinib mesylate, and angiotensin II receptor antagonists. Drug-induced psoriasis can occur with terbinafine, NSAIDs, antimalarials, ACE inhibitors, lithium and β-blockers.

The treatment for all cutaneous drug reactions is to discontinue the offending medication. Supportive treatment is indicated depending on the type of rash. Dermatology can be consulted if the morphology of the rash is difficult to determine or if there are other possible diagnoses to exclude which would require a skin biopsy.

References:

1. Revuz J, Valeyrie-Allanore L. (2008)Chapter 22: Drug Reactions. In Bolognia JL, Jorizzo JL, Rapini RP (Eds.), Dermatology, (edition 2, pgs 301-320 ). Spain: Elsevier.

2. French LE, Prins C. (2008) Chapter 21: Erythema Multiforme, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis. In Bolognia JL, Jorizzo JL, Rapini RP (Eds.), Dermatology, (edition 2, pgs 287-300). Spain: Elsevier.

3. Warnock JK and Morris DW. Adverse cutaneous reactions to antidepressants. Am J Clin Dermatol. 2002; 3(5): 329-39.