Autoimmune and other diseases — USMLE Step 2 CK Notes

Rheumatoid Arthritis

Osteopoenia/osteoporosis; Periarticular erosions

Rheumatoid nodules: found in sc tissue overlying P points

Cervical spine: subluxation, cord compression

Compressive neuropathies eg Carpel Tunnel Syndrome

Fibrotic lung disease, nodules, effusions, pulmonary HTN,

ILD most common pulm manifestation

Pyoderma gangrenosum; Anemia

Anticitrillinated peptide Abs

Rheumatoid Factor: Against Fc of IgG —> Rheumatoid factor not always present

HLA-DR4 positive

Felty syndrome: complication of seropositive RA (RF and/or Anti CCP)

NEUTROPENIA and splenomegaly

Sjogrens Syndrome (Destruction of lacrimal and salivary glands)

Dry eye sx: grittiness, foreign body sensation

Dry oral membranes

Dry skin, Raynauds, cutaneous vasculitis; Arthralgias/arthritis; Interstitial lung disease

Complications: Corneal ulceration/perforation, NHL, dental caries, RTA 1

Dx: Positive anti-Ro (SSA) or anti-La (SSB)

Salivary gland biopsy w focal lymphocytic sialoadenitis to confirm dx

Classification: Primary if no associated CTD; Secondary if comorbid CTD (SLE, RA etc)

SLE

Foetus most at risk of complete AV block if pt has Abs against SSA and SSB

—-> neonatal lupus: AV block; rash and thrombocytopoenia

Neurological issues eg cognitive dysfunc and seizures —-> CSF shows lymphocytosis ## (inflammation)

Thromboembolic events d/t vasculitis and Antiphospholipid Abs (High PTT)

Serositis; Sym migratory arthritis; Constitutional Sx

Butterfly/Discoid rash and photo sensitivity

Hemolytic anemia; thrombocytopoenia and leukopenia

Hypocomplementemia (C3 and C4)

Abs: ANA (Sensitive); Anti dsDNA & antiSm (specific)

Tx: NSAIDs; antimalarials; steroids —> immunosuppressants Ig non responsive

Fibromyalgia

Chronic widespread pain; Fatigue, impaired concentration

Trigger point tenderness eg mid trapezius, costochondral junction

3 months sx

Normal lab studies eg ESR and CK normal

Tx: exercise; TCAs

Polymyositis: muscle weak and fiery

Proximal muscle weakness -> Pain mild/absent

Peak incidence F 40-50 years

Elevated muscle enzymes: CK, aldolase and AST

AutoAbs: ANA, anti Jo 1

Involvement of upper oesophageal musculature -> dysphagia with regurgitation+aspiration

No skin manifestations cf dermatomyositis

Biopsy: Endomysial infiltrate, patchy necrosis

Tx: glucocorticoids and steroid sparing drug eg methotrexate

Cancer screen d/t paraneoplastic association

NB CK can be raised in any myopathy (No correlation with severity):

Hypothyroidism must be ruled out FIRST!

Polymyalgia Rheumatica: STIFF

Age >50 ——> old ppl are stiff!

Systemic signs

Morning Stiffness > pain in shoulders, hip girdle, neck (decreased active range of movement)

Association with Temporal Arteritis but most dont have

Elevated ESR (significantly) as in Temporal Arthritis and CRP

Normal muscle strength (cf steroid induced myopathy): Normal CK Rapid improvement with low dose glucocorticoids

Sarcoidosis -> Infiltrates everywhere!

Bilateral Hilar Adeopathy on CXR w Pulm reticular infiltrates

Erythema Nodosum; Noncaseating granulomas on biopsy

Conduction defects: AV Block most common

Constitutional sx; Uveitis; Bell’s Palsy

Parotid swelling; Elevated ACE

Diabetes insipidus and seizures; Cough, SOB and chest pain

PFT shows decreased DLCO

Hepatic sarcoidosis can cause increased AST and Alk phosphatase

Lofgren syndrome: Acute Sarcoidosis

Swollen lymph nodes in the chest, tender red nodules on the shins, fever and arthritis

All pts with parotid mass undergo CN examination

CNV and VII closely associated

—> facial droop and numbness concerning for neural invasion d/t malignancy

Most masses benign but radiation exposure (eg cancer tx) increases risk

Erythema Nodosum associated with: TB, strep infection, fungi, IBD and Behcet Disease

SCLERODERMA: Tx: Immunosuppressives

Limited cutaneous (systemic): Anti centromere Abs

Progressive Tissue Fibrosis and vascular dysfunction

Scleroderma on Head and distal arms

Prominent vascular manifestations:

Raynauds; cutaneous telangiectasias; Pulm arterial HTN-> SM hyperplasia

Esophageal dysmotility w reflux -> Decreased LES Tone

CREST Syndrome: calcinosis cutis; sclerodactyl etc

Better px

Diffuse Cutaneous: Anti SCLC 70 (topoismerase 1) Abs

Trunk and distal arms

Esophageal dysmotility w reflux

Prominent internal organ involvement: Scleroderma Renal crisis; MI ischaemia and fibrosis; ILD

Anti RNA polymerase III Abs

Worse px

Renal Crisis: RAAS

Sudden onset renal failure w/o prev hx of renal disease

Malignant HTN (HA, blurry vision, nausea) w AKI; Thrombocytopenia

MAHA or DIC —-> schistocytes and thrombocytopoenia

Normal urine/mild proteinuria

Tx: ACEI (elevated Cr not a CI in these pts; elevations common in drug initiation also)

Mixed CT Disease

Anti-RNP

Variable features of: SLE, Systemic sclerosis and Polymyositis

Juvenile RA

Adult onset Still disease is adult version: Dx of exclusion

POEMS syndrome

An uncommon disorder characterized by Polyneuropathy, Organomegaly (HSM), Endocrinopathy, Monoclonal protein, and Skin changes

Sclerotic bone lesions, extravascular volume overload, papilledema, and pulmonary disease.

Osteoarthritis: Joint aspirate non inflamm: <2000 WBC

Ankylosing Spondylitis: inflamm arthritis (WBC 5-50K) Presents with limited mobility: Not STENOSIS!

Decreased flexion at the waist; SPINAL RIGIDITY; Hyperkyphosis

Morning stiffness that improves with activity

Tenderness of sacroiliac joints; Enthesitis; Nocturnal pain

Dx: Pelvic X-RAY: widening of sacroiliac joints and subchondral sclerosis

Complications: Osteoporosis/vertebral fractures, AR and Cauda Equina

——>> INCREASED OSTEOCLASTS ACTIVITY IN CHRONIC INFLAMMATION!

Spondylolysis

Vertebral body slips forward in relation to vertebra beneath

Commonly L5 slipping over S1

Children, adolescents and those >50 years

Asymp or lumbar pain on exertion, gait issues, radiculopathic pain or urinary incontinence

Normal straight leg test

Cervical Spondylolisthesis;

Degeneration of cervical spine and osteophyte formation: compression of nerve sx

Progressive pain and weakness in a myotome and sensory loss in dematome

Dx: MRI Spine

Statin induced myopathy

Proximal muscle weakness d/t decreased co Q10 (needed for muscle energy production)

Rare rhabdomyolysis

Glucocorticoid induced myopathy

Progressive proximal weakness and atrophy w/o pain

Legs more involved

Norm inflamm markers

Hypertrophic osteoarthropathy

Polyarthropathy, digital clubbing and periostosis (excessive bone formation)

Erythema Multiforme

HSV; Mycoplasma; Sulfonamides; Malignancies

Collagen vascular diseases

Tx: Self limiting; antihistamines and topical glucocorticoids

Erythema Nodosum

Medications: Antibiotics, OCPs

Infections eg Streptococcus

Spontaneous resolution

Residual hyperpigmentation

Usually on ant legs but can be anywhere

Conditions commonly associated w digital clubbing ==> dx w Lovibond angle

Pathophysiology involves megakaryocytes that skip norm route of fragmentation within pulm circ

===> circulatory disruption from tumours/chronic lung inflammation

Megakaryocytes become entrapped in distal fingertips d/t large size and release PDGF and ## VEGF

===> Growth promoting properties that increase CT hypertrophy; capillary perm and vascularity

IBD and Cyanosis congenital heart disease (R->L Shunt)

Chronic Cutaneous Lupus erythematosus

Most common form is discoid lupus erythematosus

Can occur independently of SLE but often progresses to SLE

Scaly irreg erythematous plaques w central hypopigmentation surrounded by hyperpigmentation

Sun exposed regions of head and neck —> often also chest and arms

Lesions slowly expand over months to years —> dermal atrophy and scarring

Rash often extends to hair follicles —> scarring alopecia

Behcet Disease

Multisystem Inflamm Disorder of Young Adults

Recurrent painful oral aphthous and genital ulcers

Skin and ocular involvement common

—->> uveitis; skin lesions and exaggerated ulceration with minor trauma (pathergy)

Thrombosis major cause of morbidity

Most common in Turkish, Middle Eastern and Asian descent

Dx Clinical

Biopsy shows nonspecific vasculitis of diff sized vessels

Pagets Disease -> Disorganised bone remodelling

Asym elevation in ALK Phos in elderly patient

Osteoclast dysfunction: Focal increase in bone turnover —> DIP joint hypertrophy —> elevated bone turnover markers: PINP, urine hydroxyproline

Skull: Headaches, hearing loss, change in hat size

Spine: Spinal stenosis, radiculopathy

Long Bones: Bowing, enlargement, weakness, fracture, arthritis of Adj joints; pain

Giant cell tumour, osteosarcoma

Bone scan: Increased focal uptake

X-ray: Osteolytic or mixed lytic/sclerotic (blastic) lesions

Tx: Bisposphonates; Calcitonin less effective

Lichen Planus

5 Ps: pruritic, purple/pink, polygonal, papules and plaques

Lacy white network of lines (Wickham striae) —>> Kobner phenomenon

Locations: Skin: symmetrically on flexor surfaces (ankles, wrists)

Oral mucosa (white papules and plaques with or w/o erythema, mucosal atrophy, ulcers)

====> burning in cheeks sensation

Genitalia

Associations: Hep C, ACEIs and thiazides

Elevated LFTs

Spontaneous resolution within 2 years

Tx with topical high potency glucocorticoids eg bethamethasone

Widespread lesions need systemic glucocorticoids, phototherapy

MEN2A/B: Pheochromocytoma Needs to be removed before thyroidectomy for medullary thyroid cancer d/t risk of life threatening hypertensive crisis in surgery

Papillary thyroid cancer: MCC

Elevated thyroglobulin Ab and thyroglobulin levels sometimes seen w recurrence

Psammoma bodies

Lymphatic spread (cf follicular)

Recurrence: Increased Thyroglobulin in pts who have had thyroidectomy

Thyroid Nodule Work Up: TSH + US in all nodules

Nodule > 1cm -> poss FNA

===> Norm/High TSH w dodgy US——> FNA or US guided Biopsy (also in norm US if >2cm)

===> Low TSH —-> RAUI/uptake scan ——> cold nodule —-> FNA

Raynauds: CCBs or aspirin if at risk for digital ulceration

Exertional heat stroke Core temp >40 C Additional organ or tissue damage: Renal/hepatic failure, DIC, ARDS

Management: Rapid cooling (ice water immersion preferred)

Fluid resuscitation and electrolyte correction

No role for antipyretic Tx

Nonexertional (classic) heat stroke

Management: Evaporative cooling (Ice water immersion associated with increased mortality)

CNS dysfunction: altered mental state

Best dx for heat injuries: rectal temp

Heat Exhaustion: Hyperthermia <40 (cf heat stroke)

RF: CF (excess NaCl loss)

Medications: anticholinergics/antihistamines/TCAs/antipsychotics

NORMAL MENTAL STATUS; No coma/seizure

Management: Cool pt (air con; cool water shower); salt-containment fluids

Exercise associated postural hypotension

Cessation of exercise results in sudden decrease in Preload

Athlete collapses immediately after run etc

No LOC/Dizziness/Lightheadedness

Norm to min elevated core temperature

Tx: Trendelenburg positioning and oral hydration

Malignant hyperthermia

Genetic mutation alters control of IC Calcium

Triggered by volatile anaesthetics, succinylcholine and excessive heat

Sudden onset Masseter muscle/generalised rigidity

—> resultant muscle hypermetabolism: Fever, sinus tachy

Tachypnea, Hypercarbia (d/t increased cellular resp) resistant to increased minute ventilation

Rhabdo; Hyperkalaemia; Hyperthermia (late manifestation)

Tx: Resp support w immediate cessation of causative anaesthetic; Dantrolene

Burn Injury

Hypermetabolic response:

Increased inflamm mediators —> increased catecholamine, glucocorticoids and glucagon

Elevated basal body temperature

Myasthenia Gravis

Fluctuating and fatiguable proximal muscle weakness

Diplopia, Ptosis: Arms>Legs; normal DTRs (cf lambert)

Bulbar: Dysphagia, dysarthria —-> fatiguable chewing; nasopharyngeal regurgitation

Resp: Myathenic Crisis

Decreased AP amplitude with rep stimulation

Causes of exacerbations:

Medications: Antibiotics, NM blocking agents, Cardiac medications, MgSO4, Penicillamine

Physiologic stress: Pregnancy/childbirth, surgery (esp thymectomy), infection

Dx: AChR-Ab (v specific); Bedside ice pack test

CHEST CT for thymoma

Tx: AChE I (Pyridostigmine) +/- immunotherapy eg corticosteroids, azathioprine

MG Crisis -> Tx: Plasmapheresis or IVIg as well as corticosteroids

Lambert Eaton less likely to have ocular (ptosis) and bulbar (dysphagia, dysarthria) sx (cf MG)

AP amplitude improves w rep nerve stimulation

-> 10-15 s of isometric muscle contraction resolves weakness and DRTs reappear

Have diminished/absent DTRs (cf MG) w AN dysfunction

MC in legs; weakness not pain/tenderness

Pts must have chest CT d/t strong association with SC lung cancer

Telogen Effluivium

Most common cause of hair loss in adults

Slowed hair growth

Acute, diffuse and non inflamm

Hair shafts easily lulled out (hair pull test)

Widespread thinning of hair but scalp and hair shafts appear norm

Triggered by stressful event: weight loss, pregnancy, major illness/surgery or psych trauma

Self limited but can take up to a year

Alopecia arreata Autoimmune attack on hair bulb cells; genetic predisposition

Painless, patchy, non scarring loss

Circumscribed patches of hair loss

Hair shafts show narrowing close to surface and may be broken off

Positive hair pull test (>5-6 hairs extracted)

Management:

Mild/moderate hair loss: Topical/Intralesional corticosteroids (triamcinolone)

Extensive: Topical immunotherapy (eg diphenylcyclopropenone); oral corticosteroids

Trichorrhexis nodosa

Fragility of hair with breaking strands

Congenital or acquired (excessive heat, hair dyes, salt water)

Fractured strands with splitting fibres

Trichotillomania

Irregular patches of hair loss

Hair shafts of variable lengths

Non inflamm. Non scarring

Tx: CBT

Obstructive Sleep Apnea

Erectile dysfunction

Increased EPO

Pheochromocytoma -> Hyperglycaemia in pts w/o D/M

Osler Weber Rendu Syndrome (Hered Haemorrhagic telangiectasia)

AD

Diffuse telangiectasias (ruby coloured papules that blanch with pressure)

Recurrent epistaxis

Widespread AVMs —-> chronic hypoxaemia; digital clubbing and reactive Polycythemia

Pulm AVMs —>> massive hemoptysis

Myotonic dystrophy: AD

Trinecleotide repeat in DMPK gene (CTG repeat)

Grip myotonia; facial and distal extremity weakness; dysphagia

Temporal wasting; frontal balding and muscle atrophy; frontal balding

Arrhythmias; cataracts; excessive daytime sleepiness; testicular atrophy/infertility

Px: death d/t resp or HF depending on age of onset

Dx: Genetic testing confirmatory

Duchennes MD

Dystrophin in Skeletal, Cardiac and neural tissue

Calf psudohypertrophy (fatty replacement); Gower sign

Associations: Cardiomyopathy and Scoliosis

Wheelchair dependence by adolescence

Death 20-30 d/t resp of HF

Becker MD

X linked mutation of dystrophin gene -> partial function

See Above

ASSOCIATION: cardiomyopathy

Death d/t HF 40-50

Anabolic steroid abuse

TESTOSTERONE; syn (stanozolol, nandrolone); Precursors eg DHEA

Polycythemia w poss hypercoagulopathy

Decreased testicular function and sperm production, gynecomastia

Virilisation in F

Increased LDL and decreased HDL

Amyloidosis: EC deposition of insoluble protein fibrils:

Dx: Tissue biopsy eg abdo fat pad

AL: Produced by clonal plasma cells

AA: Secondary to chronic inflammation

ATTR: Age related or familial

AB2M: Secondary to hemodialysis

Asym proteinuria/nephrotic syn; Hepatomegaly; macroglossia; Cardiomyopathy (usually restrictive)

Periph/AN neuropathy; Waxy skin thickening; easy bruising

Sialadenosis

Benign non inflamm swelling of salivary glands

D/t overaccumulation of secretory granules in acinar cells —-> alcoholism, bulimia or malnutrition

Also d.t fatty infiltration of glands in DM or liver disease

Polycythemia

Relative Polycythemia d/t reduced plasma volume

Absolute Polycythemia d/t increased RBC mass

Primary: Polycythemia Vera

Secondary: D/t chronic hypoxia/ EPO secreting tumours

Polycythemia Vera

Aquagenic pruritus

Increased RBC turnover —> gouty arthritis

Thick blood: Erythromelalgia (burning cyanosis in hands/feet); HTN; Transient visual disturbance

Facial plethora and Splenomegaly

Low EPO w high Hb and norm O2 SATS

JAK2 mutation -> Leukocytosis and thrombocytosis

Complications: Thrombosis; myelofibrosis and acute leukaemia

Tx: serial Phlebotomy; Hydroxyurea if increased thrombus risk

Hereditary hemochromatosis

Tx: Phlebotomy; Iron chelation

Female Sexual Interest/arousal Disorder

Lack/significantly reduced sexual interest not better explained by another problem