Cutaneous Toxicities of Cancer Therapy

Cutaneous Toxicities of Cancer Therapy
By:Dr.Saiama Waqar

Outline
* Alopecia
* Hyperpigmentation
* Hand-foot syndrome
* Radiation sensitivity and recall
* Hypersensitivity
* Nail dystrophies
* Extravasation injuries
* Skin toxicity from targeted therapies
* Conclusion

Alopecia
* Drugs that target rapidly dividing cells often affect the proliferating cells in the hair follicle
* Terminal hair follicles with rapid matrix formation more affected (scalp more than body hair, eyebrows, eyelashes)
o completely lost in a short time: transplant
o gradually lost over several weeks: cyclic chemotherapy
* Methotrexate: affects the follicle melanocytes, resulting in depigmented band of hair, “flag sign”
* Visible regrowth within 3-6 months
* Often regrows with a change in color or texture (switching from straight to curly), mechanism of change unclear
* Psychologically, one of the most stressful side effects

Grading of alopecia
Grade
Minimal loss, grade 1
< 25%; obvious to the patient but not necessarily to others

Moderate loss, grade 2
25 to 50 %; obvious thinning of scalp hair but not enough to lead to the use of a wig or alternate head covering

Severe loss, grade 3

> 50% of hair lost; generally indicates the need for a wig or alternate head covering in those for whom alopecia is a major concern

Chemotherapy drugs causing alopecia

* Often
o Bleomycin
o Etoposide
o Methotrexate
o Mitoxantrone
o Paclitaxel
* Common
o Cyclophosphamide
o Daunorubicin
o Doxorubicin
o Docetaxel
o Idarubicin
o Ifosphamide
o Paclitaxel
* Infrequent
o 5-FU
o Hydroxyurea
o Thiotepa
o Vinblastine
o Vincristine
o Vinorelbine
* Rare
o procarbazine

Prevention of alopecia
* scalp tourniquets:
o pneumatic device placed around the hairline during chemo infusion
o inflated to a pressure >SBP
o Several studies: effective for preventing hair loss
+ utilized different techniques, variation in chemotherapy regimens, tourniquet pressure, sample size, and criteria to assess alopecia (data difficult to interpret)
o Side effects: headache, varying degrees of nerve compression

Prevention of alopecia
* Hypothermia with scalp icing devices:
o Vasoconstriction of scalp blood vessels, less absorption of chemo as hair follicles less metabolically active at 24C
o ice turban, gel packs, cool caps, thermocirculator, room air conditioner
o 50-80% response, though variable chemotherapy regimens and definitions of alopecia, small sample size
* Not effective in liver disease
o Delayed drug metabolism, persistent levels beyond protective period
* Scalp metastases:
o mycosis fungoides, limited to scalp. CR after chemo without scalp cooling
o 61 pts with met breast cancer and liver dysfunction, 1 pt scalp met

Preventive devices
* 1990- FDA stopped sale of these devices citing absence of safety or efficacy data
* Cranial prostheses (wigs) and scarves use encouraged

Pharmacologic interventions for alopecia
* Topical minoxidil (shorten time to maximum regrowth, did not prevent alopecia)
* AS101(NSCLC pts: garlic-like halitosis and post-infusion fevers)
* Alpha tocopherol (cardioprotection for doxorubicin, noted less alopecia)
* Topical calcitriol (cell lines- protects cancer cells)
* IL-1(rats, cytarabine, cell cycle specific, protected)
* Inhibitors of p53 (mice deficient p53, no alopecia)

Hyperpigmentation
* usually resolves with drug discontinuation
o gingival margin pigmentation seen with cyclophosphamide is usually permanent
* Patterns of pigmentation:
o Diffuse
o Local at site of infusion
* Sites of pressure /trauma
o Hydrea and cisplatin
* Busulfan
o “busulfan tan” can mimic Addison's disease.
o Although busulfan can also cause adrenal insufficiency, the skin change is 2/2 toxic effect on melanocytes
o Distinguish busulfan toxicity from true Addison's disease by normal levels of MSH & ACTH
* Liposomal doxorubicin
o macular hyperpigmentation over the trunk and extremities, including the palms and soles
o not been described with unencapsulated doxorubicin

Drugs causing hyperpigmentation

HAND-FOOT SYNDROME
* also known as palmar–plantar erythrodysesthesia (PPE)
* originally described in patients receiving high-dose cytarabine
* skin lesions begin as erythema and edema of the palms or soles and is associated with sensitivity to touch or paresthesia
* can progress to desquamation of the affected areas and significant pain

Hand foot syndrome
Acral erythema from docetaxel

Pathogenesis
* Unclear: small capillaries in the palms and soles rupture with increased pressure from walking or use, creating an inflammatory reaction
* formulation of drugs and duration of exposure can impact the incidence
o liposome-encapsulated doxorubicin more than standard formulation
o 5-FU bolus lower than CIVI and capecitabine (converted into 5-FU in vivo)

Hand foot syndrome Grading
Grade
Signs and symptoms

1 Minimal skin changes or dermatitis (eg, erythema) without pain
2 Skin changes (eg, peeling, blisters, bleeding, edema) or pain, not interfering with function
3 Skin changes with pain, interfering with function

Treatment
* No proven preventive therapy
o Pyridoxine (vitamin B6) may help reduce the incidence and severity
o Celecoxib reported to reduce incidence
* Management largely symptomatic with reduction of drug doses where appropriate
* emollients and protective gloves can be helpful

Radiation sensitization and recall
* Some chemotherapeutic agents can sensitize the skin to radiation
* recall phenomenon in previously irradiated tissue (wks to yrs after RT)
o when chemotherapy is administered
* Exact mechanism not clearly understood,
o radiation effects on the microvasculature
o altered cutaneous immunologic responses
* maculopapular eruptions with erythema, vesicles, desquamation
o mild rash to severe skin necrosis

Radiation sensitization and recall
* No specific therapy recommended
o topical corticosteroids
o Ultraviolet radiation
* caution about sun exposure
o wear protective clothing
o sunscreen products
+ 5-FU increases photosensitivity to sunlight
+ MTX may reactivate a sunburnes of cancer therapy. Curr Opin Oncol. 2002 Mar;14(2):212-6

Hypersensitivity reactions
* Can occur either from drug itself or from solubility vehicle (eg. Cremophor for paclitaxel)
* Prevention: premedicate
o Steroids (dexamethasone), H1 blockers (benadryl), H2 blockers (pepcid)
* Management of hypersensitivity reactions:
o epinephrine, hydrocortisone, and histamine blockers, along with monitoring of BP

Drugs causing hypersensitivity
NAIL DYSTROPHY
* Color changes
o Mee’s lines - transverse white
o hyperpigmentation
* Beau’s lines - transverse grooves/lines
o related to the effect of chemotherapy causing decreased nail growth
* Paronychia -inflammation of the nail fold
o Seen with cetuximab

Beau’s lines
* Onycholysis (separation of the nail plate from the nail bed)
o can be painful
o anthracyclines, taxanes (especially weekly paclitaxel), and topical 5-fluorouracil
* frozen-glove study to prevent docetaxel-induced onycholysis & cutaneous toxicity
o 45 patients, frozen glove for 90 minutes on the right hand, using the left hand as control
o Frozen glove reduced the nail and skin toxicity

Grading of nail changes
Grade
Nail changes/toxicity

1 Discoloration, ridging (koilonychias), pitting
2 Partial or complete loss of nail(s), pain in nailbed(s)
3 Interfering with ADL
Nail changes with docetaxel

Drugs causing nail changes
* Pigmentary changes
o Bleomycin
o Busulfan
o Cisplatin
o Cyclophosphamide
o Docetaxel
o Doxorubicin
o Etoposide
o Fluorouracil
o Hydroxyurea
o Idarubicin
o Ifosfamide
o Melphalan
o Methotrexate
o Mitomycin
o Mitoxantrone

* Onycholysis
o Paclitaxel
o Docetaxel
o Gemcitabine
o Capecitabine
o Cyclophosphamide
o Doxorubicin
o Etoposide
o Fluorouracil
o Hydroxyruea
* Inflammatory changes
o Gefitinib
o Cetuximab
o Capecitabine
o Docetaxel
o Paclitaxel

Extravasation injury
* The accidental extravasation of intravenous drugs occurs in approximately 0.1% to 6% of patients receiving chemotherapy
* Depending on the agent and amount, the sequelae of extravasation can range from erythema and pain to necrosis and sloughing of the skin
* The most toxic drugs are the vesicants, such as the anthracyclines, vinca alkaloids, nitrogen mustards, as well as paclitaxel and cisplatin

Vesicants and irritants
Treatment of extravasation
* immediate discontinuation of the infusion
* cooling with ice packs
o warm soaks for vinca alkaloids
* for persistent/progressive local symptoms - surgical consult
* early local debridement of can reduce extent of later injury

Extravasation of vinblastine in a 57-year-old male receiving chemotherapy for bladder cancer

Antidotes for extravasation
o topical DMSO (dimethyl sulfoxide) to enhance absorption of the extravasated drug, routine use still controversial
o Thiosulfate -nitrogen mustard extravasation (injection of a 1/6 molar solution into the area of extravasation)
o Dexrazoxane - anthracycline extravasation
* Regardless of antidote, local therapy, and prompt surgical intervention is paramount

Skin Toxicity from targeted therapy
* Because the EGFR is also expressed by basal keratinocytes, sebocytes, the outer root sheath, and some endothelial cells, agents that inhibit EGFR are associated with dermatologic side effects
Erlotinib eruption on the arms

Cutaneous reactions associated with molecularly targeted agents
Monoclonal antibodies to EGFR
Infusion reactions; acneiform eruption; paronychial inflammation; photosensitivity
* Cetuximab, panitumumab

EGFR pathway inhibitors
Acneiform eruption; paronychial inflammation; photosensitivity
* Erlotinib
* Gefitinib
* Lapatinib

Multitargeted tyrosine kinase inhibitors
Skin exanthem; SJS; acute generalized exanthematous pustulosis; Sweets syndrome; hand-foot syndrome; photosensitivity; pigmentary changes, hair depigmentation; alopecia

* Imatinib
* Dasatinib
* Sorafenib
* Sunitinib

EGFR-inhibitor induced skin changes
* (a-c) stratum corneum thickness, (d) apoptosis (apoptotic cells by 10,000).
* On-therapy (gefitinib) biopsy specimen showing (e) keratin plugs and micro-organisms in dilated infundibula and (f) acute folliculitis.

Cetuximab skin toxicity
Moderate rosacea-like eruption from cetuximab
80 year old patient receiving cetuximab and radiation for nasopharyngeal cancer

Erlotinib rash treatment
Severity of Rash
Treatment Protocol
Mild
Topical clindamycin 2%, with hydrocortisone 1% in lotion base applied twice-daily.
Moderate
Topical clindamycin 2%, with hydrocortisone 1% in lotion base applied twice-daily AND oral minocycline 100mg twice-daily for a minimum of 4 weeks and continuing thereafter as required, until resolution of the rash by one severity grade. Scalp lesions will be treated with a topical lotion clindamycin 2%, triamcinolone acetonide 0.1% in equal parts of propylene glycol and water.
Severe
Stop erlotinib therapy for 1 week and restart at 100mg once-daily. Treatment of rash with topical clindamycin 2%, with hydrocortisone 1% in lotion base applied twice-daily AND oral minocycline 100mg twice-daily for a minimum of 4 weeks and continuing thereafter as required. Scalp lesions will be treated with a topical lotion clindamycin 2%, triamcinolone acetonide 0.1% in equal parts of propylene glycol and water until resolution.
Dose modification guidelines for cetuximab (Erbitux) based upon dermatologic toxicity

Cutaneous Toxicities of Cancer Therapy.ppt

Read more...

Acute Intermittent Porphyria

Acute Intermittent Porphyria
Heme/Onc Grand Rounds
By:Jane Chawla, M.D.

History of Present Illness
Physical Exam & Laboratory Data

* VS: T 36.2 P 142 R 20 BP 178/112
* Gen: Sleepy but arousable, AxO x3
* HEENT: PERRL, EOMI, OP Clear
* Neck: Supple, no LAD
* CV: tachy, regular rhythm, no m/g/r
* Lungs: CTAB
* GI: soft, ND, mild periumbilical discomfort to palpation
* Extr: no c/c/e
* Skin: No rashes or skin lesion
* Neuro: CN II-XII intact, strength 4/5 throughout, paresthesia in bilat lower extremities, 2+ reflexes, upgoing toes



Labs:
Random Problem List?
* Hyponatremia
* Tachycardia
* Hypertension
* Elevated Creatinine
* Abdominal Pain
* Transaminitis
* Weakness
* Cortisol – wnl
Cosyntropin Stim Test – wnl
Urine lytes → SIADH
* EKG – sinus tachycardia
CT Angio (-)
Urine VMA/metanephrine (-)
* Renal Ultrasound – wnl
responded to fluids
* LFTs – Mild transaminitis
CT Abdomen/Pelvis (-)
Hepatitis panel (-)

PORPHYRIA
Heme central to understanding Porphria
* Heme is part of hemoglobin, myoglobin, catalases, peroxidases, and cytochromes
* Heme is made in every human cell (85% in erythroid cells & much of the rest in the liver)
* First enzyme in heme synthesis pathway is ALA synthetase (ALAS)
* Increase demand induces ALAS
* Heme downregulates ALAS by feedback inhibition
* Partial block in this pathway induces ALAS and causes accumulation of heme precursors upstream from block

Porphyria is a disruption in the heme pathway
* Group of metabolic diseases resulting from a partial deficiency of an enzyme in the heme biosynthetic pathway
* Seven enzymes in the pathway
* Four of the porphyrias cause acute attacks
* Increased demand for heme can precipitate attacks secondary to overproduction of toxic heme precursors (porphyrins, ALA)
* The porphyrins have no useful function and act as highly reactive oxidants damaging tissues

Overview of the Seven Porphyrias
Overview of the Four Acute Porphyrias
* Four acute porphyrias cause acute, self-limiting attacks that lead to chronic and progressive deficits
* Symptoms of acute attacks mimic other diseases and increase the potential for misdiagnosis.
* Acute porphyrias are clinically indistinguishable during acute attacks, except the neurocutaneous porphyrias (variegate porphyria and hereditary coproporphyria) can cause dermatologic changes
* Acute attacks lead to an increase in porphobilinogen (PBG) and 5-aminolevulinic acid (ALA) which can be detected in the urine
* Things that make diagnosis difficult: variable clinic course, lack of understanding about diagnostic process, and lack of a universal standard for test result interpretation

Patient Focus: Acute Intermittent Porphyria
* Most common porphyria
* Deficiency of hepatic PBG deaminase
* Autosomal dominant pattern with incomplete penetrance
* Affected individuals have a 50% reduction in erythrocyte PBG deaminase activity
* Latent prior to puberty
* Symptoms more common in females than males
* Increased urinary ALA & PBG

Prevalence in the General Population
Key Clinical Features
* Gastrointestinal symptoms - Abdominal pain (most common presenting complaint), nausea/vomiting, constipation, and diarrhea.
* Dehydration
* Hyponatremia
* Cardiovascular symptoms - tachycardia, hypertension, arrhythmias
* Neurologic manifestations - motor neuropathy, sensory neuropathy, mental symptoms, seizures.

Pathophysiology of the Acute Attack
Autonomic Nervous System
Peripheral Nervous System
Hypothalamus
Limbic area

Porphyrins excreted from liver
ALA crosses BBB
Causes oxidative damage
Accumulates in brain with neuronal and glial cell damage
Symptoms due to porphyrin
Precursor accumulation
Rather than deficiency of Heme
Porphyrins don’t Cross BBB
ALA induces liver
Damage via oxidative effects
Exacerbating Factors of Acute Attack
* Drugs that increase demand for hepatic heme (especially cytochrome P450 enzymes)
* Crash diets (decrease carbohydrate intake)
* Endogenous hormones (progesterone)
* Cigarette smoking (induces cytochrome P450)
* Metabolic stresses (infections, surgery, psychological stress)

Diagnosis of Acute Porphyria
Algorithm for Acute Porphyria Diagnosis
Treatment of the Acute Attack
* Hospitalization to control/treat acute symptoms:
o Seizures – Seizure precautions, medications?
o Electrolyte abnormalities
o Dehydration / hyponatremia
o Abdominal Pain – narcotic analgesics
o Nausea/vomiting – phenothiazines
o Tachycardia/hypertension – Beta blockers
o Urinary retention / ileus
* Withdraw all unsafe medications
* Monitor respiratory function, muscle strength, neurological status
* Mild attacks (no paresis or hyponatremia) – Intravenous 10% glucose at least 300 g per day
* Severe attacks – Intravenous hemin (3-4 mg/kg qdaily for 4 days) ASAP (can give IV glucose while waiting for IV hemin)
* Cimetidine for treatment of crisis and prevention of attacks

Hematin (Panhematin)
* Used in the treatment of the acute porphyrias since the 1970s
* Mechanism of Action: Reduces production of ALA / porphyrins by negative feedback inhibition on ALA synthetase
* Derived from outdated PRBCs from community blood banks
* Reconstitution of lyophilized hematin with 25% albumin recommended
o Reconstituted in sterile water originally –> less stable / degraded easily
o Degradation products cause an ↑ in adverse reactions
* Adverse reactions: Due to degradation products binding to endothelial cells, platelets, & coagulation factors
o Thrombophlebitis
o Anticoagulation (transient ↑ PT, bleeding may occur)
o Thrombocytopenia

* thrombophlebitis if given through large vein or central line
* Dosing:
o Acute attacks: 3-4 mg/kg/day x 4 or more days
o Max daily dose 6 mg/kg or 313 mg (1 vial) – even in obese patients
o Prevention of attacks: not well established; once or twice weekly infusions

A Study of Hemin Use in Clinical Practice

* Hemin approved under Orphan Drug Act of 1983
* Hemin removed from market in 2000 by FDA: 8/00-6/01
o Abbott Laboratories required to conduct open-label study of the safety of hemin manufactured at a new facility
o Largest trial / case series to date on hemin therapy
* Study design: “Real world” data about acute porphyria diagnosis, treatment & perceived efficacy of treatment
* Methods:
o Hemin only available through study participation – compassionate basis
o All pts judged to need hemin by their physicians were enrolled
o Confirmation of diagnosis not required
o Pts received hemin as normally prescribed by their physicians
o No specific outcome measures, exclusion criteria, or follow-up

Results of Hemin Used in Clinical Practice

* Study Population: 130 pts; 92% Caucasian; 72% female
* Precipitating factors: (40/130 pts): drugs (22%); hormonal (24%)
* Results:
o 111 pts treated for 305 acute attacks & 40 pts for prophylaxis
o Diagnostic lab findings reported in 53% (half with +results)
o Hemin regarded as effective for 73% of patients
+ Despite doses less than recommended in 20% of pts (< 3-4 mg/kg/day)
o Propylaxis with hemin in 1/3 of patients
+ Wide variability in prophylaxis regimens  lack of published guidelines
+ Among 31 receiving hemin prophylaxis for >1 month, 68% did not require subsequent tx for acute attacks
o 44% of pts experienced adverse events – most attributed to underlying disease and not hemin
+ Phlebitis was most common adverse event attributed to hematin

Long-Term Complications from Symptomatic Disease

* Neurological Sequelae
* Hypertension
* Renal failure
* Cirrhosis
* Hepatocellular carcinoma

Renal failure: Is hypertension the cause or the effect

* Debate about cause: Hypertension or another etiology?
* Increased risk of renal failure in those with more acute attacks
* Andersson et al  Population-based study (Sweden)
o Renal biopsies (n=16)  ischemic lesions, ? related to protracted vasospasm
o Theory of injury  Vasospasm from:
+ Porphyrin metabolites &
+ an upregulated SNS  ↑ urinary excretion of catecholamines during an acute attack
o By this theory, hypertension is not the sole cause of renal insufficiency

Hepatocellular Carcinoma (HCC)

* Estimated 60 to 70-fold ↑ risk of HCC in AIP patients
* Andersson  Retrospective population-based mortality study
o HCC  27% with AIP vs 0.2% deceased without AIP
o HCC more common in women (2:1)
o HCC more common in those with symptomatic disease
o Cirrhosis more common in AIP pts (12%) vs non-AIP (0.5%)
o Cirrhosis in AIP pts higher in W>M 3:1
* Retrospective analysis for genetic mutations in 17 pts with AIP & HCC (L Bjersing)
o Is PBGD a tumor suppressor gene? (No, 1 allele present in tumor)
o No mutations seen in p53 or ras (these mutations have been implicated in HCC caused by HBV or aflatoxin)
* De Siervi et al ALA is toxic to two hepatocellular cancer cell lines (HEP G2 & HEP 3B)
o Degree of cytotoxicity was directly related to concentration of ALA
o Adding hemin or D-glucose to ALA + cells decreased toxicity with HEP G2 cells
* Proposed Mechanism of cirrhosis / carcinogenesis:
o Reduced free heme pool  ↓ cytochrome P450 & antioxidant enzymes reactive oxygen species DNA damage
o ALA that accumulates can oxidize proteins & cause DNA damage

Prevention & Follow-up: Caring for Patients Between Attacks
* Avoidance of alcohol, smoking, and exacerbating drugs
* Adequate carbohydrate intake
* Medical alert bracelets/wallet cards
* Gonadotropin-releasing hormone analogues
* Iron overload from hemin (100 mg of hemin contains 8 mg of iron)
* Hepatocellular carcinoma screening
* End-Stage renal disease prevention
* Screening for Osteoporosis
o risk from GNRH analogues, immobility, malnutrition, & vitamin D deficiency

Prognosis
* Prior to 1970, fatality rates were 10% to 52%, now 10%
* Since introduction of hematin mortality has decreased
* Overall mortality in patients with acute attacks is 3-fold higher than the general population
* Delayed diagnosis and treatment contribute to higher mortality
Future Treatment Directions
* Liver transplantation
* Animal models used to mimic porphyrias with experiments to correct enzyme deficiency in tissues
* Non-viral mediated gene transfers
If You Were Asleep….Key Points to Remember
* Porphyrias are metabolic diseases resulting from a partial deficiency of an enzyme in the heme biosynthetic pathway
* Cause acute attacks secondary accumulation of heme precursors
* Clinical features: abdominal pain, tachycardia, hypertension, hyponatremia, seizures, motor neuropathy etc.
* Screen for porphyria with qualitative urinary PBG and if elevated measure quantitative urinary PBG and ALA
* Confirm diagnosis with urinary and fecal fractionated porphyrins and DNA testing
* Treat acute attacks with IV hemin
* Prevent acute attacks with smoking cessation, avoidance of inciting agents

References
Acute Intermittent Porphyria.ppt

Read more...

Eating and Sleeping Disorders

Eating and Sleeping Disorders

Eating Disorders
* 13.4% of girls and 7.1% of boys engage in disordered eating patterns.
* Paradox: As emphasis on thinness is increasing, so is the problem of obesity.
* 7 million women and 1 million men in the U.S. suffer from eating disorders.
* 15% of young women have “substantially disordered” eating attitudes and behaviors.

Factors Associated with Disordered Eating Patterns
* Being overweight
* Low self-esteem
* Depression
* Substance use
* Suicidal ideation
* More prevalent among females
* Least likely among African American females

Eating Disorders
Prevalence of Weight Concerns of Youth in Grades 5-12

Eating Disorders Anorexia Nervosa
* Anorexia Nervosa: Eating disorder characterized by:
o Refusal to maintain a body weight above the minimum normal weight for a person’s age and height.
o Intense fear of becoming obese that does not diminish with weight loss.
o Body image distortion
o In females, absence of at least 3 consecutive menstrual cycles otherwise expected to occur.
Anorexia Nervosa
* Subtypes:
o Restricting: Lose weight through dieting or exercising.
o Binge-Eating/Purging: Lose weight through use of self-induced vomiting, laxatives, or diuretics.
* Physical complications:
o Cardiac arrhythmia, low blood pressure, slow heart rate, weakened heart muscle
o Lethargy, dry skin, brittle hair, swollen parotid glands, hypothermia
o Males: Osteoporosis, substance use disorder, antisocial personality disorder
* Associated characteristics:
o Obsessive-compulsive behaviors and thoughts about food
* Associated characteristics:
o Personality disorders/characteristics:
+ Restricting: introversion, conformity, perfectionism, rigidity
+ Binge eating/purging: Extroverted, histrionic, emotionally volatile, impulse control problems, substance abuse

* Course and outcome: Highly variable
o Usually begins in adolescence
o Better outcome for binge-eating/purging
o More severe is associated with constricted/ overcontrolled profile
o ~ 44% recover completely, ~28% show some weight gain but remain underweight, poor outcome for ~ 24%
o Death: 5-20%, primarily from cardiac arrest or suicide


Eating Disorders Bulimia Nervosa
* Bulimia Nervosa: Eating disorder characterized by:
o Recurrent episodes of binge eating (rapid consumption of large quantities of food) at least twice a week for 3 months, during which the person loses control over eating and uses vomiting, laxatives, and excess exercise to control weight.
o More psychopathology than non-bulimics: Greater external locus of control, lower self-esteem and sense of personal effectiveness, negative self-image, although most are within normal weight range.

* More prevalent than anorexia
o Up to 3% of women suffer from bulimia, another 10% report some symptoms
o ~10% of bulimics are male
* Physical complications:
o Effects of vomiting: Erosion of tooth enamel, dehydration, swollen parotid glands, low potassium (can weaken heart and cause arrhythmia and cardiac arrest)
o Binge eating may cause stomach ruptures
o Gastrointestinal disturbances

* Related to:
o Coping responses to stress
o Mood disorders, especially seasonal affective disorder
o Also shares characteristics of borderline personality

* Course and outcome:
o Generally begins late adolescence/early adulthood
o Mixed, but better course than for anorexia
o Some bulimics continue to show disturbed eating patterns, low self-esteem, depressive disorder, but most recover either fully or partially.
o Poorer prognosis with associated history of substance use and longer duration before treatment.

Eating Disorders Binge-Eating Disorder (BED)
* Diagnostic category “provided for further study” in DSM-IV-TR:
o Binge Eating Disorder: Involves a large consumption of food over a short period of time at least twice weekly for 6 months
o Unlike bulimia, does not involve use of extreme behavioral attempts of vomiting, fasting, or excessive exercise as compensation for binge eating.
o Diagnosis: History of binge-eating episodes at least 2 days/week for 6 months
* Prevalence:
o Prevalence: 0.7-4% of population
o Females are 1.5 times as likely as males to have the disorder.
o Prevalent among white, African American, and American Indian women (possibly 10%), although white women are more likely to be seen for the disorder.

* Associated characteristics/risk factors:
o Overweight with history of weight fluctuation
o Prevalence: 2-5%
o Adverse childhood experiences, parental depression, vulnerability to obesity, repeated negative comments re weight and body
o Binges preceded by poor mood, low alertness, feelings of poor eating control, cravings for sweets.
o Complications: High blood pressure, high cholesterol, diabetes, and depression
* Comorbid features:
o Major depressive disorder
o Obsessive-compulsive personality disorder
o Avoidant personality disorder
* Course and outcome:
o Begins in late adolescence/early adulthood
o Positive course compared with other eating disorders: Most recover within 5 years
o Weight remains high (over time, ~1/3 meet criteria for obesity)

Eating Disorders Eating Disorder Not Otherwise Specified
* Eating Disorder Not Otherwise Specified: Eating disorders not meeting criteria for anorexia or bulimia nervosa:
o Individuals with binge-eating disorder
o Female who meets criteria for anorexia but has regular menses
o Individual who has lost significant weight but is in normal weight range

Eating Disorders Hyperphagia
* Hyperphagia: Excessive hunger and overly large amounts of food ingestion.
Eating Disorders Rumination
* Rumination: An eating disorder characterized by having the contents of the stomach drawn back up into the mouth, chewed for a second time, and swallowed again. This regurgitation appears effortless, may be preceded by a belching sensation, and typically does not involve retching or nausea. In rumination, the regurgitant does not taste sour or bitter. The behavior must exist for at least 1 month, with evidence of normal functioning prior to onset.

Eating Disorders Pica
* Pica: An appetite for non-foods (e.g., coal, soil, chalk, paper etc.) or an abnormal appetite for some things that may be considered foods, such as food ingredients (e.g., flour, raw potato, starch). In order for these actions to be considered pica, they must persist for more than one month, at an age where eating dirt, clay, etc., is considered developmentally inappropriate.
* Geophagia: Eating of dirt or clay.

Do You Have an Eating Disorder?

Overview of Major Risk Factors for Eating Disorders

Hunger and Satiety
* Ig Nobel awards celebrate the sillier side of science
* The Ig Nobel for nutrition went to a concept that sounds like a restaurant marketing ploy: a bottomless bowl of soup.
* Cornell University professor Brian Wansink used bowls rigged with tubes that slowly and imperceptibly refilled them with creamy tomato soup to see if test subjects ate more than they would with a regular bowl.
* "We found that people eating from the refillable soup bowls ended up eating 73 percent more soup, but they never rated themselves as any more full," said Wansink, a professor of consumer behavior and applied economics. "They thought 'How can I be full when the bowl has so much left in it?' "
* His conclusion: "We as Americans judge satiety with our eyes, not with our stomachs.“
* CNN.Com 10-7-07
* Societal influences:
o Mass media portray ideal female body as 5’7” 110 lbs; actual average is 5’4” 162 lbs
o Sociocultural demand for thinness
o Peer influences
o Criticisms by family members about weight
o Dating

* Body dissatisfaction:
o Males see their bodies as smaller than what they believe is preferred; females see their bodies as larger than what they believe is preferred
o Most dissatisfaction parallels low self-esteem
* Certain predisposition and characteristics lead some people to interpret images of thinness as evidence of their own inadequacy.
* Exposure to ultra-thin ideal by media can lead to:
o Internalization of that image and eating patterns intended to bring about that ideal
o Negative affect, which triggers dieting
o Social comparison, which leads to disordered eating to meet external standards of comparison.

* Top figure
o Body image ratings of women who score high on measure of distorted eating behaviors.
* Bottom Figure
o Body image ratings of women who score low on measure of distorted eating behaviors.

Route to Eating Disorders Eating Disorders
Etiology
* Family and peer influences
o Psychodynamic (for anorexia):
+ Fear of maturation:
# Growing up and separating from family
# Developing own identity
# Fulfills unconscious desire to remain a child
o Family systems: Problematic family communication patterns result in anorexia
o Socialization agents (peers and family)
o Relationship problems and role models

Eating Disorders
Etiology
* Cultural factors:
o Culture-bound (Western cultures) and other societies influenced by Western culture.
o Many African Americans seem insulated from thinness standard, but equally as likely to have binge-eating disorder.
o Internalization of U.S. societal values regarding attractiveness affects self-esteem and body dissatisfaction.
Differences in Body Image and Weight Concerns Among African American and White Females

Eating Disorders Other Etiological Factors
* Personality characteristics and negative emotional moods
* Sexual abuse
* Low self-esteem and feelings of helplessness
* Passivity, dependence, nonassertivness
* Anorexia: Perfectionism, obedience, academic and athletic success, model children
* Bulimia: Perfectionism, seasonal affective disorder
* Genetic factors: First-degree relatives

Eating Disorders Treatment
* Prevention programs:
o Goals of school-based intervention program:
+ Develop positive attitude toward one’s body
+ Become aware of societal messages re being female
+ Develop healthier eating/exercise habits
+ Increase comfort in expressing feelings
+ Develop healthy strategies to deal with stress
+ Increase assertiveness skills
o Teach females to examine consequences of gender messages
o Institutional awareness of the problem is critical
* Anorexia nervosa:
o Inpatient/outpatient depends on weight and health of individual
o Initial goal: Restore weight with psychological support
+ Nutritional/physical rehabilitation
+ Identify/understand dysfunctional attitudes
+ Improve interpersonal/social functioning
+ Address comorbid psychopathology/psychological conflicts

* Anorexia nervosa:
o Family therapy: Parents involved in meal planning, reduce criticism (understanding seriousness of anorexia), negotiate new relationship patterns, move toward separation and individuation.

* Bulimia nervosa:
o Identify conditions contributing to purging
o Identify physical conditions resulting from purging
o Normalize eating pattern and eliminate binge-purge cycle
* Bulimia nervosa:
o Cognitive-behavioral therapy and use of antidepressants:
+ Encourage eating 3 or more balanced meals a day
+ Reduce rigid food rules and body image concerns
+ Develop cognitive and behavioral strategies

* Binge-Eating Disorder
o Similar to treatments for bulimia with fewer physical complications
o Because most are overweight, therapy programs try to help individual lose weight
o Three phases:
+ Determine underlying cognitive factors
+ Use cognitive strategies to change distorted beliefs about eating
+ Relapse prevention strategies


Primary Sleep Disorders
* Most adults require 8 hours of sleep to function optimally.
* Insufficient sleep results in lapses in attention, vigilance, and deterioration of performance.
* Five stages of sleep:
o Stage 1 (5%): Transition from wakefulness to sleep
o Stage 2 sleep (50%)
o Stages 3-4 (10-20%): Deepest level
o Rapid eye movement (REM-20-25%): Dream sleep

Primary Sleep Disorders Dyssomnias
* Most problems are either inability to initiate or maintain sleep at night or excessive daytime sleepiness.
* Dyssomnias: Difficulties in getting to sleep, maintaining sleep, or complaints of excessive sleepiness during the day.


Primary Sleep Disorders Primary Insomnia
* Primary Insomnia: Characterized by difficulty getting to sleep, maintaining sleep, or having nonrestorative sleep for at least one month, causing clinically significant distress in social, occupational, or other areas of functioning.
o Causative factors: caffeine, alcohol, heavy meals, exercising 2 hours before bedtime, stress, intrusive/ uncontrollable cognitive activity, altered sleep habits
o Highest rate: 52% of older adults
* Many people with primary insomnia have undiagnosed sleep Apnea or Restless Leg Syndrome.
* RLS (which is also sometimes referred to as Jimmy Legs, spare legs or "the kicks") may be described as uncontrollable urges to move the limbs in order to stop uncomfortable, painful or odd sensations in the body, most commonly in the legs. Moving the affected body part eliminates the sensation, providing temporary relief. The sensations and need to move may return immediately after ceasing movement, or at a later time. RLS may start at any age, including early childhood, and is a progressive disease for a certain percentage of sufferers, although it has been known for the symptoms to disappear permanently in some sufferers.


Primary Sleep Disorders Primary Hypersomnia
* Primary Hypersomnia: Characterized by excessive daytime sleepiness or prolonged nighttime sleep for at least one month, causing significant distress or impairment in social, occupational, or other important areas of functioning.
o Compelling need to nap during the day that provides no relief from sleepiness.
o Results in problems with driving, work performance, or social functioning.

Primary Sleep Disorders Narcolepsy
* Narcolepsy: Characterized by overwhelming need for daytime sleep even when adequate sleep occurs at night; daily for at least 3 months, together with at least 2 of the following:
o Irresistible drowsiness/falling asleep without warning
o Cataplexy
o Sleep paralysis during wakefulness
o Hypnogogic hallucinations before falling asleep

Primary Sleep Disorders Breathing-Related Sleep Disorder

* Breathing-Related Sleep Disorder: Excessive sleepiness caused by sleep disruption through abnormalities of breathing during sleep
o Obstructive Sleep Apnea: Upper-airway obstruction during sleep
+ Undiagnosed in ~75% of treatable cases
+ Disruptive snoring, breathing pauses, gasping, excessive daytime sleepiness
+ Obstruction of airway prevents breathing during sleep
o Central sleep apnea syndrome
o Central alveolar hypoventilation syndrome

Primary Sleep Disorders Circadian Rhythm Sleep Disorder
* Circadian Rhythm Sleep Disorder: Pattern of recurrent sleep disruption caused by disruption of the biological sleep-wake cycle or mismatch between internal “clock” for sleeping and waking and environmental demands.
o Jet lag, shift work
o Associated with major disasters (e.g., Exxon Valdez oil spill)


Primary Sleep Disorders Dyssomnias Not Otherwise Specified

* Dyssomnias Not Otherwise Specified: Do not meet criteria for specific dyssomnia, but produce significant impairment:
o Insomnia caused by environmental factors
o Excessive sleepiness caused by sleep deprivation
o Restless leg syndrome
o Periodic limb movement disorder


Primary Sleep Disorders Parasomnias
* Parasomnias: Activation of physiological systems at inappropriate times during the sleep-wake cycle.
* Generally involve activation of the autonomic nervous system, including cognitive processes during sleep or sleep-wake transitions.

Primary Sleep Disorders Parasomnias
* Nightmare disorder: Nightmares several times/week during REM sleep.
o 3% of preschoolers and school-aged children
* Sleep Terror Disorder: Vivid nightmares during first third of deep sleep (non-REM); child screams with terror, is not fully aroused, and does not remember what happened.
o ~6% of children, disappears in adolescence
o In adults age 20-30 it has a chronic course
* Sleepwalking Disorder: Motor activity ranging from sitting up to getting out of bed and walking about while still asleep.
o ~2% of school-aged children sleepwalk at least a few nights a week
o Up to 30% of children sleepwalk at least once
o 1-5% of children have sleepwalking disorder
o Tends to disappear in adolescence; in adults it will have a chronic waxing/waning course.

* Parasomnias Not Otherwise Specified:
o REM sleep behavior disorder: Violent motor behavior during REM sleep
o Sleep paralysis/inability to move during transition from wakefulness and sleep


Primary Sleep Disorders Etiology and Treatment of Dyssomnias
* Etiology: Subclinical anxiety and depression, environmental changes, health and behavioral habits; for some etiology is unknown but may include:
o Cognitions or intrusive, uncontrollable thoughts
o Personality and psychological adjustment problems
o Lifestyle factors
o Nocturnal activities that interfere with sleep
* Treatment for specific disorders:
o Excessive sleepiness (narcolepsy or hypersomnia): Stimulants, though more success with hypersomnia than narcolepsy.
o Insomnia: Sleep pills, which tend to become ineffective over the long-term.
o Sleep apnea: Avoid medications, alcohol and other substances; lose weight if overweight; sleep on side rather than back; pressure mask during sleep may also help with moderate and severe apnea.

* Treatment for RLS and PLMD: Behavioral treatment, medications for RLS
* Treatment for sleep disorders generally:
o Relaxation/focusing procedures
o Changing mental state prior to bedtime
o Slow deep breaths
o Eliminate distractions
o Avoid daytime naps, caffeine late in day, heavy meals/exercise/alcohol/nicotine 2 hours before bedtime.


Eating and Sleeping Disorders.ppt

Read more...