# 062 # Pages 1526-1550 Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Diagnosis • Diagnosis is made clinically • anti-melanocyte antibodies • can be confirmed using a skin biopsy. Management • sun block for affected areas of skin • camouflage make-up • topical corticosteroids may reverse the changes if applied early • there may also be a role for topical tacrolimus and phototherapy, although caution needs to be exercised with light-skinned patients Vitiligo ____________________________________________________ Angular stomatitis • Angular stomatitis describes erythema and fissuring of the skin adjacent to the angle of the mouth. • The most common cause is Candida infection • also associated with:  allergy, seborrhoeic dermatitis,  vitamin B deficiencies,  iron deficiency. ____________________________________________________ Venous ulceration • Venous ulcers are secondary to venous stasis and chronic stretching of the walls of the superficial veins. These eventually become thinner and ulcerate. • typically seen above the medial malleolus The incidence of venous leg ulceration is higher in: • obese patients • history of varicose veins • history of deep vein thrombosis Ulcers occur owing to: • venous stasis • secondary increase in capillary pressure • fibrosis • poorly nourished skin particularly over areas such as the medial malleolus Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Chapter 10 Dermatology Investigations • ankle-brachial pressure index (ABPI) is important in non-healing ulcers to assess for poor arterial flow which could impair healing a 'normal' ABPI may be regarded as between 0.9 - 1.2. Values below 0.9 indicate arterial disease. Interestingly, values above 1.3 may also indicate arterial disease, in the form of false-negative results secondary to arterial calcification (e.g. In diabetics) Management • compression bandaging, usually four layer (only treatment shown to be of real benefit) • The mainstay of treatment of venous ulceration is compression therapy, which aims to improve venous return and thereby reduce venous hypertension. • The patient should always have their Doppler's and ABPI (ankle brachial pressure index) prior to compression. The ABPI should be greater than 1 before compression bandaging is used (this excludes significant arterial disease. • oral pentoxifylline, a peripheral vasodilator, improves healing rate • small evidence base supporting use of flavinoids • little evidence to suggest benefit from hydrocolloid dressings, topical growth factors, ultrasound therapy and intermittent pneumatic compression ____________________________________________________ Pressure ulcers Overview • Pressure ulcers develop in patients who are unable to move parts of their body due to illness, paralysis or advancing age. • They typically develop over bony prominences such as the sacrum or heel. The following factors predispose to the development of pressure ulcers: malnourishment incontinence lack of mobility pain (leads to a reduction in mobility) • The Waterlow score is widely used to screen for patients who are at risk of developing pressure areas. It includes a number of factors including body mass index, nutritional status, skin type, mobility and continence. Grading of pressure ulcers the following is taken from the European Pressure Ulcer Advisory Panel classification system. Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Grade Findings Grade Non-blanchable erythema of intact skin. Discolouration of the skin, warmth, oedema, induration or hardness may also be used as indicators, particularly on individuals with darker skin Grade Partial thickness skin loss involving epidermis or dermis, or both. The ulcer is superficial and presents clinically as an abrasion or blister Grade Full thickness skin loss involving damage to or necrosis of subcutaneous tissue that may extend down to, but not through, underlying fascia. Grade Extensive destruction, tissue necrosis, or damage to muscle, bone or supporting structures with or without full thickness skin loss Management • a moist wound environment encourages ulcer healing. Hydrocolloid dressings and hydrogels may help facilitate this. The use of soap should be discouraged to avoid drying the wound • wound swabs should not be done routinely as the vast majority of pressure ulcers are colonised with bacteria. The decision to use systemic antibiotics should be taken on a clinical basis (e.g. Evidence of surrounding cellulitis) • consider referral to the tissue viability nurse • surgical debridement may be beneficial for selected wounds ____________________________________________________ Keloid scars Keloid scars are tumour-like lesions that arise from the connective tissue of a scar and extend beyond the dimensions of the original wound Predisposing factors • ethnicity: more common in people with dark skin • occur more commonly in young adults, rare in the elderly • common sites (in order of decreasing frequency): sternum, shoulder, neck, face, extensor surface of limbs, trunk • Keloid scars are less likely if incisions are made along relaxed skin tension lines* *Langer lines were historically used to determine the optimal incision line. They were based on procedures done on cadavers but have been shown to produce worse cosmetic results than when following skin tension lines Treatment • early keloids may be treated with intra-lesional steroids e.g. triamcinolone • excision is sometimes required Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Chapter 10 Dermatology ____________________________________________________ Increased skin fragility • Increased skin fragility is seen in a number of disorders and is used as a clinical test in bullous disorders (Nikolsky's sign). • Other causes include: pemphigus vulgaris porphyria cutanea tarda drug reactions (especially pseudoporphyria). • Other causes of increased skin fragility (not associated with bullae) include:  long term corticosteroid therapy, Ehlers-Danlos syndrome curvy (vitamin C deficiency). ____________________________________________________ Basal cell carcinoma (BCC) Overview • Basal-cell carcinomas are the most common malignant skin tumour and are related to excessive sun exposure most commonly occurs in elderly patients with sun-damaged skin. • Lesions are also known as rodent ulcers • characterised by slow-growth and local invasion. Metastases are extremely rare. • BCC is the most common type of cancer in the Western world. • BCC is more commonly seen on the upper lip. Genetics • environmental and genetic factors are believed to predispose patients to BCC • Basal cell carcinoma is associated with mutations in the Hedgehog signaling pathway. • Up to 70% of people with sporadic BCC without Gorlin syndrome have patched PTCH1 gene mutations as a result of UV radiation exposure. Features • many types of BCC are described. The most common type is nodular BCC. • sun-exposed sites, especially the head and neck account for the majority of lesions • initially a pearly, flesh-coloured papule with telangiectasia • may later ulcerate leaving a central 'crater' • characterized histologically by palisading nuclei. Palisading nuclei consist of parallel rows of elongated nuclei. Management • surgical removal Mohs surgery for is useful for minimizing the amount of safety margin excised. • curettage • cryotherapy • topical cream: imiquimod, 5- fluorouracil • radiotherapy BCC VS SCC Basal cell carcinoma Squamous cell carcinoma Most common 2nd most common Present in upper part of face Present in lower part of face (appear most often on the lower lip, ear, and nose.) Does not metastasize and kill by local invasion(rodent ulcer) presents as a “pearly” papule or nodule that grows slowly with shiny appearance with telangiectasias and an umbilicated center or ulcer ____________________________________________________ Squamous cell carcinoma (SCC) Overview • SCC is the second most common non-melanoma skin cancer worldwide (after basal cell cancer). • SCC is the most common oral cancer. • More common in elderly males. • It is possible to get SCC on any part of the body, including the inside of the mouth, lips, and genitals. • Women frequently get SCC on their lower legs. Precursor and variants of SCC: • Actinic keratosis presents as hyperkeratotic grey-white plaques and is a precursor lesion to squamous cell carcinoma of the skin. Precursor lesions for SCCs are called actinic (or sun-damage) keratosis Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Can metastasize usually hyperkeratotic scaly lesion with crusting and ulceration. often well-defined, superficial, discrete, and hard lesions arising from an indurated, rounded, and elevated base Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Chapter 10 Dermatology • Keratoacanthoma is a cup-shaped form of squamous cell carcinoma of the skin that develops rapidly and resolves spontaneously. Risk factors • photo-exposed skin such as face and lower lips. often caused by ultraviolet B-light, which can mutate DNA via the formation of pyrimidine dimers. exposure to ultraviolet radiation (UV), especially UVB Mutations in the p53 tumour suppression gene commonly affects the lower lip. • The incidence of skin cancer has been increasing among Caucasians but remains relatively low in people of color.  Light-skinner, non-Hispanic white populations experience higher rates of SCC than darker people of color. Low incidence in darker skins due to photo-protection provided by increased epidermal melanin, which filters twice as much ultraviolet (UV) radiation When skin cancer occurs in people of color, patients often present with an advanced stage, and thus, worse prognosis in comparison to Caucasian patients • Chronic immunosuppression more common in patients who have received an organ transplant. • old scars or burns may arise from areas of Bowen’s disease and sometimes in the margin of a chronic leg ulcer. (SCC) arising on a scar is termed a Marjolin ulcer.  Marjolin ulcer is typically aggressive and associated with a poor prognosis. • arsenic exposure • ionizing radiation • HPV infection • chronic infections, particularly those associated with chronically draining sinuses. • actinic keratoses and Bowen's disease • Inherited syndromes: eg: xeroderma pigmentosum and albinism • smoking Features • usually appears as a scaly or crusty area of skin, with a red, inflamed base. Diagnosis • Excision biopsy is essential for accurate diagnosis. shows keratin pearl appearance. The presence of keratin pearls indicates that the tumor is well-differentiated and carries a better prognosis.  undifferentiated tumor would contain almost entirely atypical cells that have lost their keratin producing function and thus keratin pearls would be absent. Treatment • Treatments include non-surgical destruction (e.g., using cryotherapy), topical chemotherapy, traditional surgical excision, and Mohs micrographic surgery. • Surgical excision with 4mm margins if lesion <20mm in diameter. If tumour >20mm then margins should be 6mm. • Mohs surgery is the best surgical treatment to minimize the loss of normal tissue. • Radiotherapy is the treatment of choice in patients who are poor surgical candidates. • Chemotherapy is used as adjuvant therapy in high risk patients Prevention • Sunscreen is used to minimize risk of developing SCC. Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Prognosis Good Prognosis Poor prognosis Well differentiated tumours Poorly differentiated tumours <20mm diameter >20mm in diameter <2mm deep >4mm deep No associated diseases Immunosupression for whatever reason Keratoacanthoma (KA) Overview • Keratoacanthoma (KA) is a relatively common low-grade malignancy that originates in the pilosebaceous glands and resembles squamous cell carcinoma (SCC) pathologically. • Some experts support classifying KA as a variant of invasive SCC. • Keratoacanthoma is a benign epithelial tumour. • It is believed to develop from the hair follicle, • more common in males. • They are more frequent in middle age and do not become more common in old age (unlike basal cell and squamous cell carcinoma) • KA is characterised by rapid growth over a few weeks to months, followed by spontaneous resolution over four to six months in most cases. • Lesions typically are solitary and begin as firm, roundish, skin-coloured or reddish papules that rapidly progress to dome-shaped nodules with a smooth shiny surface and a central crateriform ulceration or keratin plug that may project like a horn. Features - said to look like a volcano or crater • initially a smooth dome-shaped papule • rapidly grows to become a crater centrally-filled with keratin Treatment • The most suitable management Urgent referral to dermatology • Spontaneous regression of keratoacanthoma within 3 months is common, often resulting in a scar. • Should be urgently excised as it is difficult clinically to exclude squamous cell carcinoma. Removal also may prevent scarring. Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Chapter 10 Dermatology ____________________________________________________ Actinic keratoses Overview • Actinic, or solar, keratoses (AK) is a common premalignant skin lesion that develops as a consequence of chronic sun exposure • Less than 10% of actinic keratoses progress to invasive squamous cell carcinoma. Features • small, crusty or scaly, lesions • may be pink, red, brown or the same colour as the skin • typically on sun-exposed areas e.g. temples of head • multiple lesions may be present Management • prevention of further risk: e.g. sun avoidance, sun cream • fluorouracil cream: typically a 2 to 3 week course. The skin will become red and inflamed - sometimes topical hydrocortisone is given following fluorouracil to help settle the inflammation • topical diclofenac: may be used for mild AKs. Moderate efficacy but much fewer side-effects • topical imiquimod: trials have shown good efficacy • cryotherapy • curettage and cautery ____________________________________________________ Malignant melanoma Overview • Melanocytes are positioned in the basal layer of the epidermis • Melanoma is the third most common skin cancer, but is the most common cause of skin cancer-related death. • Up to 20% of patients develop metastatic disease. The mnemonic of ABCDE regarding characteristics of a melanoma are as follows: • A - Asymmetry - one half of the lesion does not match the other half • B - Border irregularity • C - Colour variegation - pigmentation is not uniform • D - Diameter- a diameter 7 mm warrants investigation although changes in size are also important • E - Evolution - evolving size or changes in characteristics such as nodules. Prognostic factors The invasion depth of a tumour (Breslow depth) is the single most important factor in determining prognosis of patients with malignant melanoma Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Breslow Thickness Approximate 5 year survival < 1 mm 95-100% 1 - 2 mm 80-96% 2.1 - 4 mm 60-75% > 4 mm 50% Treatment • Vemurafenib is a small molecule inhibitor of BRAF oncogene that can be found in melanoma. As such, Vemurafenib is used to treat metastatic melanoma. Lentigo maligna • Lentigo maligna is a type of melanoma in-situ. • It typically progresses slowly but may at some stage become invasive causing lentigo maligna melanoma. • Lentigo maligna melanoma occurs on the sun-exposed skin areas (usually the face) of elderly patients Acral lentiginous melanoma • The acral lentiginous melanoma is normally seen on the sole of the foot, and occasionally on the palm of the hand • It is characterised by a raised darker area surrounded by a paler macular (lentiginous) area that may extend for several centimetres around the raised area • There are two clinical clues that lead us to suspect this diagnosis: the patient's race and the location of the lesion. 1. Acral lentiginous melanoma is more common in African-Americans and Asians than other forms of melanoma. 2. the lesion is located in an area not exposed to sunlight (the sole of the foot is the most common place for this type of melanoma). Other notes • Patients with a strong family history of melanoma are more likely to harbor a mutation in the cyclin-dependent kinase inhibitor 2A tumor-suppressor gene (CDKN2A mutation) that codes for p16, which prevents progression through G1. • Periungual melanomas occur in the area of the nailbed • Hutchinson’s sign (brown pigmentation on the nailfold) is an important pointer to malignant melanoma • Superficial spreading melanoma is the commonest type, consisting of an irregular brown, black or blue–black lesion with some intermingled inflammation • Nodular melanoma: the most rapidly growing and aggressive variant and may contain relatively little melanin pigment associated with higher rates of metastasis and poorer outcomes than classic melanoma. Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Chapter 10 Dermatology ____________________________________________________ Moles • Uniform pigmentation is not in itself a suspicious feature of a mole, but colour variegation and irregular border are two of many suspicious features. ____________________________________________________ Systemic mastocytosis Results from a neoplastic proliferation of mast cells Features • urticaria pigmentosa - produces a wheal on rubbing (Darier's sign) • flushing • abdominal pain • monocytosis on the blood film Diagnosis • raised serum tryptase levels • urinary histamine ____________________________________________________ Angiosarcoma • Angiosarcomas are malignant vascular tumours most commonly seen in elderly men. • most commonly occur on the scalp and forehead. • present an infiltrative vascular patch or plaque with super-imposed nodules which may bleed with minor trauma. • poor prognosis. • Angiosarcomas can also occur in areas of chronic lymphoedema. Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad ____________________________________________________ Pyogenic granuloma Overview • relatively common benign skin lesion • benign vascular lesion of the skin and mucosa. • The name is a double misnomer - the lesion is neither pyogenic nor a granuloma. • There are multiple alternative names but perhaps 'eruptive haemangioma' is the most useful. • Pathologically, it is an inflammatory lesion composed of granulation tissue and chronic inflammatory cells. Etiology • unknown • associated with trauma and pregnancy Epidemiology • more common in women and young adults Features • initially soft, round, bright red spot • usually solitary lesions, • Lesions often grow rapidly (over weeks), • tender and bled easily when touched. Localization • The most common location are: fingers (commonly involve the digits) mucosal surfaces of the mouth inner surfaces of the nose. Treatment • lesions associated with pregnancy often resolve spontaneously post-partum • other lesions usually persist. • surgical excision Removal methods include curettage and cauterisation, cryotherapy, excision Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Chapter 10 Dermatology ____________________________________________________ Skin disorders associated with malignancy Paraneoplastic syndromes associated with internal malignancies: Skin disorder Associated malignancies Acanthosis nigricans Gastric cancer Acquired ichthyosis Lymphoma Acquired hypertrichosis lanuginosa Gastrointestinal and lung cancer Dermatomyositis Ovarian and lung cancer Erythema gyratum repens Lung cancer Erythroderma Lymphoma Migratory thrombophlebitis Pancreatic cancer Necrolytic migratory erythema Glucagonoma Pyoderma gangrenosum (bullous and non-bullous forms) Myeloproliferative disorders Sweet's syndrome Haematological malignancy e.g. Myelodysplasia - tender, purple plaques Tylosis Oesophageal cancer Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Acrokeratosis paraneoplastica A widespread psoriatic-type rash involving the ears is suggestive of acrokeratosis paraneoplastica. • Most acrokeratosis paraneoplastica cases are associated with squamous cell carcinoma of the upper one third of the respiratory or GI tract, i.e. the oropharynx, larynx, lungs or oesophagus. The symptoms of indigestion and food sticking fit best with a diagnosis of oesophageal carcinoma. ____________________________________________________ Otitis externa Otitis externa is a common reason for primary care attendance in the UK. Causes of otitis externa include: • infection: bacterial (Staphylococcus aureus,Pseudomonas aeruginosa) or fungal • seborrhoeic dermatitis • contact dermatitis (allergic and irritant) Features • ear pain, itch, discharge • otoscopy: red, swollen, or eczematous canal Management • Initial management topical antibiotic or a combined topical antibiotic with steroid if the tympanic membrane is perforated aminoglycosides are traditionally not used. many ENT doctors disagree with this and feel that concerns about ototoxicity are unfounded if there is canal debris then consider removal if the canal is extensively swollen then an ear wick is sometimes inserted • Second line options include consider contact dermatitis secondary to neomycin oral antibiotics if the infection is spreading taking a swab inside the ear canal empirical use of an antifungal agent • Malignant otitis externa more common in elderly diabetics. In this condition there is extension of infection into the bony ear canal and the soft tissues deep to the bony canal. Intravenous antibiotics may be required. ____________________________________________________ Livedo reticularis (LR) Definition • A vascular syndrome that can be caused by either benign autonomic dysregulation of cutaneous perfusion or pathological obstruction of blood vessels. Pathophysiology • Physiological livedo (idiopathic livedo): primary livedo Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Chapter 10 Dermatology Autonomic dysregulation (functional disturbance) causing slowed cutaneous perfusion in response to external factors (i.e., cold). Triggered by cold, regresses after application of warmth. • Pathological livedo (livedo racemosa): secondary livedo Localized obstructions slow the blood flow (organic disturbance). Persists after warming the skin. Features • Patchy, reticulated, vascular network with a red-blue or violaceous discoloration of the skin. • A “fish-net like” mottling of the skin • Occur more in women than in men and usually in the 3rd decade of life. • Occurs most often in the lower extremities Causes It is mainly idiopathic (primary livedo reticularis is the most common cause) Causes Secondary livedo reticularis: • Obstruction / vasculopathy Antiphospholipid syndrome o Livedo racemosa is the most common dermatologic presentation in patients with antiphospholipid syndrome (APS), presenting in 25% of patients with primary APS and in 70% of patients with SLE-associated APS. Cryoglobulinaemia Polycythaemia rubra vera Multiple myeloma Cold agglutinin disease Protein C and S deficiency Antithrombin III deficiency Disseminated intravascular coagulation Haemolytic uraemic syndrome Emboli (DVT , cholesterol emboli and septic emboli) Hypercalcaemia (calcium deposits) Infections (syphilis, tuberculosis, Lyme disease) • Autoimmune / vasculitis / connective tissue disease Small, medium and large vessel vasculitis. SLE Dermatomyositis Rheumatoid arthritis Polyarteritis nodosa Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad • Drugs Amantadine (dopamine agonist used to treat Parkinson disease) causes livedo through arteriolar vasospasm provoked by catecholamines. Minocycline • Associations LR preceded the onset of repeated attacks of pancreatitis in a patient with chronic pancreatitis. Primary fibromyalgia Congenital hypogammaglobulinemia. Treatment • Physiological : warmth. bath PUVA is a therapeutic option with the possibility of some success. • Pathological : treat underline cause Livedo reticularis that does not regress after application of warmth is indicative of an underlying vascular disease and requires treatment. ____________________________________________________ Hyperhidrosis describes the excessive production of sweat Management options include • topical aluminium chloride preparations are first-line. Main side effect is skin irritation • iontophoresis: particularly useful for patients with palmar, plantar and axillary hyperhidrosis • botulinum toxin: currently licensed for axillary symptoms • surgery: e.g. Endoscopic transthoracic sympathectomy. Patients should be made aware of the risk of compensatory sweating ____________________________________________________ Seborrheic keratosis • Seborrheic keratoses are the most common benign tumor in older individuals. • and they develop from the proliferation of epidermal cells. • No specific etiologic factors have been identified. • Typical features include a warty and waxy surface with surface crypts and a stuck on appearance. • They typically have an appearance of being stuck on the skin surface. • Because they begin at a later age and can have a wart-like appearance, seborrheic keratoses are often called the “barnacles of aging. • Most commonly they are several • Can growths anywhere on the skin, except the palms and soles. Most often on the chest, back, head, or neck. • Commonly used treatments include Curettage and cautery (C&C), and cryotherapy (for thinner lesions). Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Chapter 10 Dermatology multiple seborrheic keratoses in an autosomally dominant mode of inheritance. ____________________________________________________ Solar keratosis • hyperkeratotic lesion with underlying erythema. • bleed when scratched • Progression of these lesions to squamous cell skin cancer is slow • Topical 5-FU cream used twice a day for 3–4 weeks usually achieves clearance of the lesion. • Diclofenac gel requires a more prolonged treatment period (up to 12 weeks), meaning that it is the second-choice option for compliance reasons. It is useful where coverage of a larger area of skin is required. solar keratosis (on scalp of elderly) Telogen phase • The telogen phase is the resting phase of the hair follicle. • Due to extreme stress →shedding of hair leading to loss of thickness →loss of hair. • It occurs as a normal phenomenon one to three months after pregnancy. • No treatment is required (only reassurance) and hair thickness eventually recovers without further intervention. Third edition Notes & Notes For MRCP part 1 & 11 By Dr. Yousif Abdallah Hamad Psychiatry Updated Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Chapter 11 Psychiatry Unexplained symptoms • Conversion disorder typically involves involuntary loss of motor or sensory function without a physiologic cause , often following an acute stressor. • Dissociative disorder involves psychiatric symptoms e.g. Amnesia, fugue, stupor • Malingering patients consciously fake or exaggerate for secondary gain, such as money, sick leave, or avoidance of responsibilities. • Somatisation disorder ________________________________________________________________ Eating disorders: Anorexia nervosa Definition • Anorexia nervosa is an eating disorder characterised by an intense fear of gaining weight and distorted body image resulting in calorie restriction and severe weight loss leading to inappropriately low body weight (BMI < 18.5 kg/m2), with the inability to recognize the seriousness of their significantly low body weight. Subtypes Restricting type Binge-eating/purging type • No binge eating or purging over a 3month period • weight loss is achieved by excessive dieting, exercise, or fasting • Presence of binge eating or purging over a 3-month period • weight loss is achieved by vomiting, diuretic and laxative abuse, or enemas Features • Significant low BMI < 18.5 using strategies that include restrictive eating, purging, and excessive exercise • Fear of weight gain • Lack of awareness of the seriousness of low body weight • Distorted body image and believe they are "fat" when they usually are very thin. Use of laxatives to drive weight loss is common, and a purgative screen is therefore a logical next step. Complications (due to weight loss & malnutrition) • Endocrine: central hypogonadism (Hypothalamic suppression) → estrogen deficiency → ↓ LH & FSH → estrogen deficiency leads to:  secondary Amenorrhea (functional hypothalamic amenorrhea)  osteoporosis →↑stress fractures. Euthyroid sick syndrome, hypothyroidism Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad • Cardiac: structural : cardiac mass, ↓cardiac chamber volumes, mitral valve prolapse, and pericardial effusion. Functional: bradycardia, hypotension and QT interval prolongation. So dizziness is the most concerning symptom • Refeeding syndrome: occur due to fluid and electrolyte shifts, marked by hypophosphatemia → arrhythmias. Lab findings • Electrolyte imbalances: ↓ potassium, ↓ sodium, ↓ chloride, ↓ phosphate, ↓ magnesium, ↑ bicarbonate (metabolic alkalosis) • ↑↑Cortisol, • ↑↑growth hormone (due to GH resistance), • ↑↑ glucose (impaired glucose tolerance) • Hypercholesterolaemia • Hypercarotinaemia • low T3 with normal T4 and TSH • hypoalbuminaemia Differential diagnosis • Bulimia nervosa not significantly underweight; rather, most of patients are at normal weight or overweight do not have excessive restrictive caloric intake behavior that is characteristic of patients with anorexia nervosa, so complications of starvation are unlikely Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Chapter 11 Psychiatry Treatment • first-line → Cognitive behavioral therapy & Nutritional support • second line (antipsychotic) → olanzapine Tricyclic antidepressants should not be used because of their potential cardiotoxicity. Bupropion should not be used because it is associated with a higher incidence of seizures in patients with eating disorders. Do not offer medication as the sole treatment for anorexia nervosa. The best, most easily obtainable measure of clinical improvement in a patient with anorexia nervosa → a weight gain of 1 pound (0.45 kg) per week. The antidepressant bupropion lowers the seizure threshold. It is, therefore, contraindicated in individuals with eating disorders who are at an increased risk of developing seizures secondary to dehydration and electrolyte imbalances. Eating disorders: Bulimia nervosa Definition • Bulimia nervosa is a type of eating disorder characterised by episodes of binge eating followed by intentional vomiting to prevent weight gain. Features • BMI is normal or slightly elevated (≥ 18.5 kg/m2) • Induced vomiting →dorsal hand calluses (Russell sign), erosion of the teeth , malloryWeiss syndrome • Parotid gland hypertrophy • ↑Serum amylase • Electrolyte disturbances (eg,K+,Cl−), metabolic alkalosis Treatment • Cognitive behavioural therapy (CBT) • Do not offer medication as the sole treatment for bulimia nervosa. Parotid hypertrophy and erosion of the teeth are the most common physical signs of Bulimia nervosa and may prompt diagnosis. Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Hypomania vs mania The presence of psychotic symptoms differentiates mania from hypomania Mania Psychotic symptoms Mania and Hypomania delusions of grandeur Mood Predominately elevated irritable Auditory hallucinations Speech & Thought  Pressured  Flight of ideas  Poor attention Behaviour  Insomnia  Loss of inhibitions: risk-taking  Increased appetite Antipsychotics • Antipsychotics act as dopamine D2 receptor antagonists, blocking dopaminergic transmission in the mesolimbic pathways. • Conventional antipsychotics are associated with problematic extrapyramidal side-effects which has led to the development of atypical antipsychotics such as clozapine Extrapyramidal side-effects • Parkinsonism • acute dystonia (e.g. torticollis, oculogyric crisis) affects about 2% of patients. Administer procyclidine • akathisia (severe restlessness) • tardive dyskinesia (late onset of choreoathetoid movements, abnormal, involuntary), may occur in 40% of patients, may be irreversible, most common is chewing and pouting of jaw Specific warnings when antipsychotics are used in elderly patients: • increased risk of stroke (especially olanzapine and risperidone) • increased risk of venous thromboembolism Other side-effects • antimuscarinic: dry mouth, blurred vision, urinary retention, constipation • sedation, • weight gain • raised prolactin: galactorrhoea, block dopamine D2 receptors block dopamine's action on the pitutary reduces inhibition of prolactin secretionhyperprolactinaemia. • Amenorrhoea, infertility • loss of libido, and erectile dysfunction. • impaired glucose tolerance • neuroleptic malignant syndrome: pyrexia, muscle stiffness • reduced seizure threshold (greater with atypicals) • prolonged QT interval (particularly haloperidol) Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Chapter 11 Psychiatry Typical antipsychotics Typical Antipsychotics High Potency Antipsychotics (in Descending Order) Advantages Disadvantages Unique Features Haloperidol Fewer side effects of sedation and hypotension High association with extrapyramidal symptoms  Able to use as long-acting depot injections  Can be given IM in acute situations Fluphenazine Perphenazine Chlorpromazine Lower frequency of extrapyramidal side effects Greater incidence of anticholinergic side-effects, hypotension, sedation Corneal deposits Thioridazine  Retinal deposits  QT prolongation Atypical antipsychotics atypical antipsychotics such as olanzapine/risperidone/clozapine have been associated with hyperglycaemia and insulin resistance. • Clozapine: Most effective anti-psychotic Decreased suicide risk.  Agranulocytosis • Adverse effects of atypical antipsychotics: weight gain. clozapine is associated with agranulocytosis. • Risperidone is a high-affinity D2 and 5-HT-2 receptor antagonist Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad ________________________________________________________________ Neuroleptic malignant syndrome (NMS) • It may also occur with dopaminergic drugs (such as levodopa) for Parkinson's disease, usually when the drug is suddenly stopped or the dose reduced. A patient with P/H/O parkinson's disease, deteriorate 1 – 2 days after admission to hospital for other condition →neuroleptic malignant syndrome (NMS) as a result of not taking her parkinson's medication →do Creatine kinase to confirm the diagnosis • Onset usually in first 10 days of treatment or after increasing dose • Renal failure may occur secondary to rhabdomyolysis • Raised creatine kinase in most cases. the most important investigation to be performed Management • stop antipsychotic • IV fluids to prevent renal failure • dantrolene may be useful in selected cases thought to work by decreasing excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor, and decreasing the release of calcium from the sarcoplasmic reticulum • bromocriptine, dopamine agonist, may also be used • levodopa preparations may be beneficial Neuroleptic malignant syndrome Serotonin syndrome • develops over days to weeks. • develops over 24 hours. • characterized by sluggish neuromuscular responses (rigidity, bradyreflexia). • characterized by neuromuscular hyperreactivity (tremor, hyperreflexia, myoclonus). • resolution typically requires an average of nine days. • resolution typically requires less than 24 hours . Serotonin syndrome • Myoclonus is the distinguishing feature of serotonin syndrome (found only in serotonin syndrome). • Occur in those taking therapeutic doses of SSRIs, as part of drug-drug interaction (e.g. the addition of: ondansetron, amphetamine, cocaine, meperidine(Pethidine), dextromethorphan, fentanyl, buspiron, ergot alkaloids, lithium, L-dopa, LSD, St. John’s Wort), or following intentional self-poisoning with SSRI. • treatment stopping any serotinergic agents using benzodiazepines for agitation consideration of use of serotonin antagonists such as cyproheptadine if there is severe autonomic disturbance. Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad Chapter 11 Psychiatry Antidepressants • SSRIs are the first-line treatment for the vast majority of patients with depression Selective serotonin reuptake inhibitors (SSRIs) • Mechanism of action inhibition of serotonin reuptake in synaptic cleft →↑serotonin levels primarily act at the 5HT transporter protein • Drugs Fluoxetine Paroxetine Sertraline Citalopram Escitalopram • Indications First-line treatment for major depressive disorder Generalized anxiety disorder Obsessive-compulsive disorder Post-traumatic stress disorder Somatic symptom disorder Panic disorder Gambling disorder Premature ejaculation Premenstrual dysphoric disorder Binge-eating disorder • Side effects Sexual disorders (anorgasmia, erectile or ejaculatory dysfunction, ↓ libido) Diarrhea, nausea, vomiting  gastrointestinal symptoms are the most common side-effect Sleep disorders Headache Increased risk of bleeding  proton pump inhibitor should be prescribed if a patient is also taking a NSAID Serotonin syndrome Risk of suicide attempt a few days after commencing treatment with an SSRI  In major depressive disorder, the greatest risk for suicide occurs after a partial response to antidepressants.  Usually, energy and motivation return before a subjective improvement in mood occurs, and a patient who has been too apathetic to act on suicidal rumination may, at this point, attempt suicide. patients should be counselled to be vigilant for increased anxiety and agitation after starting a SSRI • Contraindications risk of serotonin syndrome if given concomitantly within 14 days of MAOIs, linezolid, or methylene blue use • Additional information must usually be taken for 4–6 weeks before symptom reduction is seen Notes & Notes for MRCP By Dr. Yousif Abdallah Hamad citalopram (although ↑QT interval) and fluoxetine are currently the preferred SSRIs sertraline is useful post myocardial infarction as there is more evidence for its safe use in this situation than other antidepressants nice advice 2017 For people who also have a chronic physical health problem, consider using citalopram or sertraline as these have a lower propensity for interactions. SSRIs should be used with caution in children and adolescents. Fluoxetine is the drug of choice when an antidepressant is indicated • Citalopram and the QT interval citalopram and escitalopram are associated with dose-dependent QT interval prolongation and should not be used in those with:  congenital long QT syndrome;  known pre-existing QT interval prolongation; or  in combination with other medicines that prolong the QT interval the maximum daily dose is now 40 mg for adults; 20 mg for patients older than 65 years; and 20 mg for those with hepatic impairment • Interactions NSAIDs: NICE guidelines advise 'do not normally offer SSRIs', but if given coprescribe a proton pump inhibitor warfarin / heparin: NICE guidelines recommend avoiding SSRIs and considering mirtazapine  the SSRIs least likely to cause drug interactions with warfarin appear to be sertraline and citalopram. aspirin: see above triptans: avoid SSRIs fluoxetine and paroxetine have a higher propensity for drug interactions • Antidepressant Follow-up After initiation of antidepressant therapy patients should normally be reviewed by a doctor after 2 weeks. For patients under the age of 30 years or at increased risk of suicide they should be reviewed after 1 week. If a patient makes a good response to antidepressant therapy, they should continue on treatment for at least 6 months after remission as this reduces the risk of relapse. • Selective serotonin reuptake inhibitor discontinuation syndrome When stopping a SSRI, the dose should be gradually reduced over a 4-week period  This not necessary with fluoxetine due to its longer half-life. Paroxetine has a higher incidence of discontinuation symptoms. SSRI withdrawal syndrome typically begins within 24-48 hours after withdrawal, Discontinuation symptoms  Psychiatric (anxiety, insomnia, mood lability, vivid dreams)  Gastrointestinal (nausea, vomiting , diarrhoea cramping pain), and  Neurological (dizziness, headache, paraesthesia, dystonia, tremor).