Differentials

Common

Insomnia disorder

History

difficulty in initiating sleep, waking frequently, poor concentration, depressed mood

Exam

decreased alertness, red and puffy eyes, absence of physical signs suggesting organic illness

1st investigation
  • none:

    diagnosis based on history and clinical examination

Other investigations

    Depression

    History

    depressed mood, sadness, emotional distress, anxiety, irritability, anhedonia, feeling hopeless, loss of self-esteem, sleep problems, appetite troubles, weight loss or gain, loss of energy, poor concentration, suicidal ideation, symptoms of psychosis or mania

    Exam

    psychomotor slowing, agitation, blunted affect

    1st investigation
    • 2-item screening tool (PHQ-2):

      positive if 1 answer is yes

      More
    • PHQ-9 screening tool:

      PHQ-9 score: 5 to 9: mild depression; 10 to 14: moderate depression; 15 to 19: moderately severe depression; ≥20: severe depression

      More
    Other investigations

      Iron-deficiency anaemia

      History

      asthenia, hair loss, dyspnoea, menorrhagia, dysphagia (Plummer-Vinson's syndrome)

      Exam

      pallor, tachycardia, systolic ejection murmur, blue sclera

      1st investigation
      • FBC:

        decreased Hb and Hct; decreased MCV, MCH, and MCHC

        More
      • ferritin:

        decreased

      Other investigations

        Iron deficiency without anaemia

        History

        asthenia, hair loss, menorrhagia

        Exam

        examination may be unrevealing

        1st investigation
        • FBC:

          normal

        • ferritin:

          <67 picomol/L (<30 nanograms/mL)

          More
        Other investigations

          Chronic heart failure

          History

          decreased exercise tolerance, dyspnoea on exertion, orthopnoea, paroxysmal nocturnal dyspnoea, previous myocardial infarction

          Exam

          oedema, displaced cardiac apex, hepatojugular reflux, jugular venous distension, S3 gallop, pulmonary rales, hepatomegaly

          1st investigation
          • brain natriuretic peptide (BNP)/N-terminal prohormone BNP (NT-proBNP):

            elevated

          • chest x-ray:

            cardiomegaly, pulmonary oedema, pleural effusion

          • ECG:

            anterior q waves or bundle branch block, atrial or ventricular arrhythmias, left axis deviation, ventricular hypertrophy

            More
          Other investigations
          • FBC:

            normal or abnormal

            More
          • echocardiogram:

            may show systolic and/or diastolic dysfunction, valve lesions, signs of pericardial injury or cardiomyopathy

          Diabetes mellitus

          History

          polyuria, polydipsia, weakness, myalgia, weight loss, polyphagia, nausea, vomiting, altered state of consciousness, decreased vision

          Exam

          signs of volume depletion (dry mucous membranes, decreased skin turgor); confusion (in ketoacidosis or non-ketotic hyperglycaemia); neuropathy, retinopathy

          1st investigation
          • fasting blood glucose level:

            ≥6.9 mmol/L (≥125 mg/dL)

            More
          • HbA1c:

            ≥48 mmol/mol (≥6.5%)

            More
          Other investigations
          • oral glucose tolerance test:

            2-hour post-load blood sugar ≥11 mmol/L (≥199 mg/dL)

            More

          Hypothyroidism

          History

          weakness, cold intolerance, dry skin, hair and eyebrow loss, weight gain, constipation, peri-orbital swelling, depression, hoarseness, dyspnoea on exertion, menstrual disturbance (menorrhagia), cognitive dysfunction

          Exam

          bradycardia, hypothermia, hypotension (if severe); diastolic hypertension, slow movement and speech, delayed relaxation of tendon reflexes, peri-orbital oedema, enlargement of the tongue, goitre; myxedema coma (unusual)

          1st investigation
          • TSH:

            elevated

            More
          Other investigations
          • T4 (serum free thyroxine):

            low or normal

            More

          Hyperthyroidism

          History

          decreased weight despite increased appetite, emotional lability, oligomenorrhoea, heat intolerance

          Exam

          weight loss, hyper-reflexia, tachycardia, irregularly irregular pulse (atrial fibrillation), fine tremor, goitre may be present

          1st investigation
          • TSH:

            low

          • free T4 and/or free T3:

            elevated

          Other investigations
          • radioiodine scan:

            shows increased uptake in areas of hyperfunction

          EBV infection

          History

          fever, sore throat, rash, drowsiness, myalgia, loss of appetite

          Exam

          generalised lymphadenopathy, hepatosplenomegaly, rash

          1st investigation
          • FBC:

            leukocytosis, atypical lymphocytes

          • LFTs:

            elevated AST and ALT

          • monospot test:

            positive

            More
          Other investigations
          • Epstein-Barr antibodies:

            positive

            More

          Influenza infection

          History

          winter season, fever with cough, sore throat, runny nose, current influenza outbreak

          Exam

          decreased breath sounds, presence of rales (uncommon, occurs in secondary bacterial pneumonia)

          1st investigation
          • none:

            diagnosis is clinical (febrile respiratory illness during a known seasonal influenza outbreak)

            More
          Other investigations
          • rapid diagnostic tests:

            positive for influenza A and/or influenza B, depending on particular test used

          • viral culture:

            detection of influenza virus or viral antigen

          • direct immunofluorescent-antibody staining:

            detection of influenza virus

          • reverse transcription polymerase chain reaction:

            detection of influenza virus

          • enzyme immunoassay:

            detection of influenza virus

          • serology:

            4-fold or greater rise in antibody titre from acute to convalescent sample

          • chest x-ray:

            normal in uncomplicated cases; may show infiltrates consistent with pneumonia in complicated cases

          Long COVID

          History

          breathlessness, fatigue, post-exertional malaise and/or poor endurance, 'brain fog', cough, chest pain, headache, palpitations, arthralgia, myalgia, paraesthesia, abdominal pain, diarrhoea, insomnia and other sleep difficulties, lightheadedness, impaired daily function and mobility, pain, mood changes, anosmia or dysgeusia, menstrual cycle irregularities

          Exam

          new onset postural orthostatic tachycardia syndrome (POTS), tachycardia, fever, rash (e.g., urticaria, 'covid toes'), cognitive impairment, muscle weakness, generalised focal neurological signs

          1st investigation
          • blood count, electrolytes, liver and renal function, CRP, vitamin D, vitamin B12:

            usually normal in long covid; investigations to exclude other causes of fatigue

          • SARS-CoV-2 antibodies:

            positive

            More
          • fatigue severity scale:

            score ≥4 indicates fatigue

          • modified Medical Research Council Dyspnoea Scale (mMRC):

            0 = dyspnoea only with strenuous exercise; 1 = dyspnoea when hurrying or walking up a slight hill 2 = walks slower than people of the same age because of dyspnoea or has to stop for breath when walking at own pace; 3 = stops for breath after walking 91 m or after a few minutes; 4 = too dyspnoeic to leave house or breathless when dressing​

          Other investigations
          • chest x-ray:

            may show pulmonary sequelae of acute infection including loss of lung volume, fibrosis, ground glass opacification and reticular opacities/peripheral atelectasis

            More
          • Montreal Cognitive Assessment (MoCA):

            abnormal below 26

          • high-sensitivity troponin:

            elevated in infarction and myocarditis

            More
          • D-dimer to rule out pulmonary emboli:

            abnormal above 500 ng/mL

            More

          Medicine-induced fatigue

          History

          history of taking medicine associated with fatigue: most commonly antihistamines, antihypertensives, anti-arrhythmics, antidepressants, anti-emetics, antiepileptics, corticosteroids, diuretics, or neuroleptic agents

          Exam

          no specific findings

          1st investigation
          • medicine withdrawal if safely achievable:

            resolution of fatigue

            More
          Other investigations

            Alcohol dependence

            History

            history of alcohol misuse

            Exam

            malnutrition, ascites, jaundice, peripheral neuropathy, palmar erythema, splenomegaly, telangiectasias, caput medusae

            1st investigation
            • alcohol use disorders identification test (AUDIT):

              score ≥8 suggests hazardous drinking; use in primary care

              More
            • CAGE questionnaire:

              positive if answer to any 1 question is yes

              More
            Other investigations
            • FBC:

              macrocytosis, leukopenia, and/or thrombocytopenia

              More
            • gamma-GT, ALT, AST:

              elevation of ALT, AST, and gamma-GT with serum AST > ALT (ratio >2)

            • carbohydrate-deficient transferrin (CDT):

              positive if >2.5%

              More

            Drug dependence

            History

            history of drug misuse, insomnia (particularly associated with nicotine, caffeine, marijuana, cocaine, and heroin misuse), aggressive behaviour, agitation, depressed mood; specific symptoms related to type of drug

            Exam

            clinical signs vary depending on the type of drug

            1st investigation
            • urine toxicology:

              positive for specific drug

              More
            • blood toxicology:

              positive for specific drug

              More
            Other investigations
            • HIV serology:

              positive or negative

              More
            • hepatitis B and C studies:

              positive or negative serology

              More

            HIV infection

            History

            often asymptomatic; fever, myalgia, diarrhoea, unexplained weight loss, rashes; history of high-risk sexual activity (multiple partners, unprotected or male-male intercourse) or intravenous drug use

            Exam

            persistent generalised lymphadenopathy, other signs vary depending on the stage of disease

            1st investigation
            • HIV antibodies:

              positive; may be negative in early disease

              More
            Other investigations
            • HIV RNA:

              positive

              More

            Acute myocardial ischaemia

            History

            history of cardiovascular risk factors: hypertension, obesity, diabetes mellitus, smoking, family history of heart disease; chest pain, nausea, vomiting, sweating, dizziness, shortness of breath

            Exam

            variable, may appear pale or grey, hypotension

            1st investigation
            • ECG:

              ischaemic changes: ST elevation, inverted T waves

            • troponin:

              elevated in infarction

            • chest x-ray:

              may be normal or have evidence of pulmonary oedema

            Other investigations
            • coronary angiography:

              vessel narrowing, occluding thrombus in acute infarction

            Atrial fibrillation

            History

            exercise intolerance, palpitations, lightheadedness, syncope, dyspnoea

            Exam

            tachycardia, signs of heart failure: oedema, displaced cardiac apex, hepatojugular reflux, jugular venous distension, pulmonary rales

            1st investigation
            • ECG:

              absent P waves; presence of fibrillatory waves that vary in size, shape, and timing; irregularly irregular QRS complexes

              More
            Other investigations
            • chest x-ray:

              cardiomegaly, in particular left atrial enlargement; signs of heart failure; other precipitating pathology, such as pneumonia

            • TSH:

              normal or decreased

              More

            COPD

            History

            dyspnoea, chronic cough, smoking history

            Exam

            barrel chest, findings on auscultation: hyper-resonance, decreased breath sounds, wheezing, rhonchi, decreased oxygen saturation on pulse oximetry

            1st investigation
            • spirometry:

              FEV1/FVC ratio <70% with no evidence of reversibility with bronchodilator

              More
            • chest x-ray:

              hyperinflation

              More
            Other investigations
            • FBC:

              elevated haematocrit, possible increased WBC count

              More

            Tuberculosis

            History

            fever, chills, chronic cough, weight loss, night sweats; history of travel to endemic areas, HIV infection, or immunosuppression

            Exam

            pulmonary signs: tachypnoea, decreased breath sounds, crackles, dullness to percussion; extrapulmonary: findings dependent on site affected, generalised lymphadenopathy common

            1st investigation
            • chest x-ray:

              may demonstrate atelectasis from airway compression, pleural effusion, consolidation, pulmonary infiltrates, mediastinal or hilar lymphadenopathy, upper zone fibrosis

              More
            • sputum acid-fast bacilli smear and culture:

              presence of acid-fast bacilli (Ziehl-Neelsen stain) in specimen.

              More
            • acid-fast bacilli smear and culture of extrapulmonary biopsy specimen:

              positive

              More
            • nucleic acid amplification tests (NAAT):

              positive for M tuberculosis

              More
            Other investigations
            • bronchoscopy and bronchoalveolar lavage:

              positive for acid-fast bacilli

              More
            • lateral flow urine lipoarabinomannan (LF-LAM) assay:

              positive

              More
            • contrast-enhanced chest computed tomography scan:

              primary TB: mediastinal tuberculous lymphadenitis with central node attenuation and peripheral enhancement, delineated cavities; postprimary TB: centrilobular nodules and tree-in-bud pattern

              More

            Toxoplasmosis

            History

            mild fever, chills, sweats; rarely: headaches, myalgia, sore throat, rash; most cases are asymptomatic

            Exam

            bilateral cervical adenopathy, pharyngitis, maculopapular rash, hepatosplenomegaly

            1st investigation
            • serology:

              positive IgG and IgM antibodies

              More
            Other investigations

              Stroke

              History

              weakness of the face, blurred vision, diplopia, decreased vision, sudden paresis/paralysis of limbs, headache, vomiting

              Exam

              abnormal neurological examination, difficulty in speaking: slurred speech, confused speech; paresis/paralysis of limbs

              1st investigation
              • CT head:

                ischaemic: hypo-attenuation (darkness) of the brain parenchyma; loss of grey matter-white matter differentiation, and sulcal effacement; haemorrhagic: enhancing lesion

              Other investigations

                Uncommon

                Obstructive sleep apnoea/hypopnoea syndrome (OSAHS)

                History

                snoring, diurnal somnolence, agitation and sweating at night, headache, morning xerostomia (dry mouth) and sore throat, depressed mood, irritability, loss of libido; total score of ≥11 on Epworth sleepiness scale supports the diagnosis

                Exam

                elevated BP, obesity, nasal obstruction, macroglossia, tonsillar hypertrophy, obstruction by the palate, low soft palate, retrognathism, micrognathia

                1st investigation
                • polysomnography:

                  apnoea/hypopnoea index ≥15 episodes/hour (in the absence of symptoms) or ≥5 events/hour associated with the typical symptoms of OSA

                  More
                • portable multichannel sleep tests:

                  Respiratory Event Index (REI) of ≥15 episodes/hour or REI ≥5 with symptoms or comorbidities

                  More
                Other investigations
                • fibre-optic endoscopy:

                  may see nasal polyps or tumours, or hypertrophic lingual tonsils

                Obesity hypoventilation syndrome (OHS)

                History

                obesity (body mass index [BMI] ≥ 30 kg/m²), dyspnoea, nocturia, lower extremity oedema, excessive daytime sleepiness, fatigue, loud disruptive snoring, witnessed apnoeas, waking headaches

                Exam

                mild hypoxaemia awake (arterial oxygen saturation less than 94% on air), with significant hypoxaemia when asleep, awake daytime hypercapnia, unexplained polycythaemia

                1st investigation
                • serum bicarbonate:

                  >24 mmol/L (>24 mEq/L)

                  More
                • arterial blood gas:

                  PaCO₂ >45 mmHg

                  More
                Other investigations
                • polysomnography:

                  demonstrates hypoventilation, particularly during REM sleep

                  More

                Restless legs syndrome

                History

                limb discomfort at rest, involuntary limb movement, restlessness, disturbed sleep, depressed mood

                Exam

                no specific findings

                1st investigation
                • none:

                  diagnosis is clinical

                Other investigations

                  Coeliac disease

                  History

                  diarrhoea, steatorrhoea, abdominal pain, weight loss

                  Exam

                  pallor, easy bruising, aphthous stomatitis; abdominal distension

                  1st investigation
                  • anti-tissue transglutaminase antibodies:

                    elevated titre

                    More
                  • IgG DGP or IgA/IgG DGP (deamidated gliadin peptide):

                    elevated titre

                    More
                  Other investigations
                  • small intestine biopsy:

                    presence of intra-epithelial lymphocytes, villous atrophy, and crypt hyperplasia

                    More

                  Addison's disease

                  History

                  weakness, anorexia, weight loss, nausea, vomiting, abdominal pain, fever, myalgia, arthralgia

                  Exam

                  signs of volume depletion (dry mucous membranes, decreased skin turgor), hypotension, tachycardia, hyper-pigmentation

                  1st investigation
                  • morning serum cortisol:

                    decreased

                    More
                  • serum electrolytes:

                    decreased sodium; elevated potassium, creatinine, and urea

                  Other investigations
                  • short ACTH stimulation test:

                    cortisol <497 nanomol/L (<18 micrograms/dL)

                    More

                  Hypopituitarism

                  History

                  symptoms vary depending on underlying cause: energy loss, muscle weakness, decreased sweating, anorexia, weight loss or weight gain, abdominal pain, reduction in amount of axillary and pubic hair in women, erectile dysfunction, oligomenorrhoea/amenorrhoea, breast atrophy, loss of libido, infertility, cold intolerance, dry skin, polyuria, polydipsia, nocturia

                  Exam

                  may have increased central adiposity, dry skin, reduced muscle mass and strength, visual field defects, circulatory collapse if acute presentation

                  1st investigation
                  • LH:

                    low

                  • FSH:

                    low

                  • oestrogen:

                    low

                    More
                  • TSH:

                    low

                  • free T4 and T3:

                    low

                  • basal serum cortisol:

                    low

                  Other investigations
                  • testosterone:

                    low

                  • prolactin:

                    low or high

                    More
                  • cortisol reserve:

                    low (with cosyntropin stimulation)

                  • FBC:

                    anaemia

                  • metabolic panel:

                    may show hyponatraemia, hyperkalaemia, hypoglycaemia

                  • insulin tolerance test:

                    reduced growth hormone and cortisol responses

                    More
                  • urine specific gravity:

                    low in diabetes insipidus

                  • water deprivation test:

                    urine osmolality less than serum osmolality following water deprivation

                    More
                  • desmopressin test:

                    after desmopressin, urine osmolality increases in central diabetes insipidus

                    More

                  Myelodysplastic syndrome

                  History

                  dyspnoea, leg swelling, bleeding, history of bacterial or fungal infections

                  Exam

                  petechiae, purpura, leg oedema

                  1st investigation
                  • FBC and differential:

                    pancytopenia, abnormal cells, anaemia

                  Other investigations
                  • bone marrow biopsy:

                    hyperactive or hypoactive marrow and abnormal cells

                  Chronic myeloid leukaemia

                  History

                  fever, weight loss, night sweats, history of bruising

                  Exam

                  hepatosplenomegaly, petechiae, purpura

                  1st investigation
                  • FBC and peripheral blood smear:

                    elevated or abnormal WBC count, low platelet count; myeloid maturing cells, elevated basophils and eosinophils

                  Other investigations
                  • bone marrow biopsy:

                    granulocyte hyperplasia

                    More

                  Non-Hodgkin's lymphoma

                  History

                  persistently enlarged lymph nodes, possibly extranodal sites, constitutional or B symptoms (fevers, night sweats, and/or weight loss) and occasionally pruritus

                  Exam

                  generalised, local, or regional lymphadenopathy; hepatosplenomegaly

                  1st investigation
                  • lymph node excision biopsy:

                    histology and immunohistochemistry, cytogenetics, flow cytometric and molecular genetic analysis confirm the type and grade of lymphoma

                  Other investigations
                  • FBC:

                    evaluation for cytopenias

                    More
                  • LDH:

                    elevated

                    More
                  • bone marrow biopsy:

                    indicated for staging in newly diagnosed lymphoma

                  • CT scan of neck, chest, abdomen, and pelvis:

                    evaluation of the extent of lymphadenopathy and performance of accurate staging

                    More
                  • whole-body positron emission tomography (PET scan) or integrated PET/CT:

                    regions affected by lymphoma will appear to be highly metabolically active on PET scan

                  • HIV serology:

                    may be positive

                    More
                  • hepatitis B and C serology:

                    may be positive

                    More

                  Hodgkin's lymphoma

                  History

                  painless cervical and/or supraclavicular lymphadenopathy in a young adult is common; constitutional or B symptoms (fevers, night sweats, and/or weight loss), occasionally pruritus, possibly pain following alcohol ingestion at sites of lymphadenopathy

                  Exam

                  generalised, local, or regional lymphadenopathy; hepatosplenomegaly

                  1st investigation
                  • lymph node excision biopsy:

                    Hodgkin's cell can be a characteristic Reed-Sternberg cell, or variants such as the lacunar cell in the nodular sclerosis subtype; in nodular lymphocyte-predominant Hodgkin's lymphoma, the characteristic cell is the lymphocytic and histiocytic cell (popcorn cell)

                  Other investigations
                  • FBC:

                    evaluation for cytopenia

                  • bone marrow biopsy:

                    indicated for staging in newly diagnosed lymphoma

                  • CT scan of neck, chest, abdomen, and pelvis:

                    evaluation of the extent of lymphadenopathy and performance of accurate staging

                    More
                  • whole-body positron emission tomography (PET scan) or integrated PET/CT:

                    regions affected by lymphoma will appear to be highly metabolically active on PET scan

                  Cytomegalovirus infection

                  History

                  usually asymptomatic unless immunocompromised; fever, malaise, night sweats, arthralgia, weakness, weight loss; symptoms specific to infection site: for example, reduced vision, pneumonia, encephalitis, diarrhoea

                  Exam

                  dependent on site of infection; includes lymphadenopathy and hepatosplenomegaly, retinal changes

                  1st investigation
                  • CMV IgM and IgG antibodies:

                    positive

                    More
                  Other investigations
                  • CMV polymerase chain reaction:

                    positive

                  • CMV antigenaemia test:

                    positive

                    More
                  • blood culture:

                    positive

                    More
                  • urine culture:

                    positive

                    More
                  • tissue biopsy:

                    positive for CMV viral particles

                    More

                  Lyme disease

                  History

                  fever, lethargy, headache, myalgia, neck stiffness, inflammation of large joints

                  Exam

                  erythema migrans: bull's-eye lesion(s)

                  1st investigation
                  • immunofluorescence assay (IFA):

                    antibodies to Borrelia burgdorferi

                  • ELISA:

                    positive

                  Other investigations
                  • Western blot:

                    positive

                    More
                  • 2nd ELISA:

                    positive

                    More

                  Brucellosis

                  History

                  history of animal contact or ingestion of unpasteurised dairy products; fever, sweats, malaise, arthralgia, depression, weight loss

                  Exam

                  fever, lymphadenopathy, hepatosplenomegaly

                  1st investigation
                  • blood culture:

                    positive for Brucella

                  Other investigations
                  • bone marrow culture:

                    positive for Brucella

                  Chronic renal disease

                  History

                  weakness, pruritus, loss of appetite, nausea, vomiting, headache, dizziness, muscle pain, cramps, arthralgia, dyspnoea

                  Exam

                  generalised oedema, elevated BP, purpura, mental status changes

                  1st investigation
                  • serum creatinine:

                    elevated

                  Other investigations

                  Multiple sclerosis

                  History

                  unilateral visual disturbance, leg cramping, strange sensory phenomena, bladder and bowel dysfunction

                  Exam

                  increased muscle tone, increased deep tendon reflexes, abnormalities on eye examination

                  1st investigation
                  • MRI brain and spinal cord:

                    hyper-intensities in the peri-ventricular white matter

                  Other investigations

                    Parkinson's disease

                    History

                    tremor, bradykinesia, dysphagia, blurred vision

                    Exam

                    tremor, bradykinesia, rigidity, postural instability, hypomimia (masked facial expression), speech impairment, sialorrhoea, hypometric saccades, impaired vestibulo-ocular reflex, micrographia, dystonia, myoclonus

                    1st investigation
                    • none:

                      diagnosis is clinical

                      More
                    Other investigations

                      Fibromyalgia

                      History

                      widespread musculoskeletal pain, abdominal pain, chest pain, pelvic pain, bladder symptoms suggestive of cystitis

                      Exam

                      >11 out of 18 tender points present on palpation of soft tissues

                      1st investigation
                      • none:

                        diagnosis is strictly clinical

                      Other investigations

                        Vitamin D deficiency (osteomalacia)

                        History

                        often asymptomatic, diffuse bone pain, myalgia, muscle weakness

                        Exam

                        fractures, diffuse bony tenderness; skeletal deformities are rare in adults

                        1st investigation
                        • serum vitamin D 25-hydroxy level:

                          <50 nanomol/L (20 nanograms/mL)

                        Other investigations
                        • DEXA:

                          reduced bone density, thinning of the cortex

                          More

                        Systemic lupus erythematosus

                        History

                        rash, fever, weight loss, hair loss, arthralgia, chest pain and dyspnoea, abdominal pain, nausea, vomiting, diarrhoea

                        Exam

                        oral ulcers, alopecia, butterfly rash, discoid rash, photosensitive rash, lymphadenopathy, hypertension, oedema, Raynaud's phenomenon

                        1st investigation
                        • ANA, dsDNA, Smith antigen:

                          positive

                          More
                        Other investigations

                          Primary biliary cirrhosis

                          History

                          personal history or family history of autoimmune disease, history of hypercholesterolaemia, pruritus, sleep disturbance, family history of primary biliary cirrhosis, dry eyes and mouth, postural dizziness/blackouts

                          Exam

                          hepatomegaly; less commonly, signs associated with advanced liver disease and portal hypertension (e.g., skin hyperpigmentation, splenomegaly, jaundice, xanthelasmata)

                          1st investigation
                          • LFTs:

                            elevated gamma-GT, bilirubin, and Alk phos

                          • anti-mitochondrial antibodies:

                            present

                            More
                          Other investigations

                            Underlying malignancy (non-lymphoma)

                            History

                            history of weight loss, possible family history of cancer, additional symptoms dependent on cancer type

                            Exam

                            variable; lymphadenopathy and/or hepatosplenomegaly may be present; more specific findings related to cancer type

                            1st investigation
                            • variable (e.g., mammography, CT scan, pathology):

                              depends on cancer type

                            Other investigations

                              Chronic fatigue syndrome (myalgic encephalomyelitis)/systemic exertion intolerance disease

                              History

                              severe disabling fatigue lasting >6 months; not due to ongoing exertion, not relieved with rest, reduced levels of activity, symptoms present for >50% of time; may involve memory/cognitive impairment, myalgia, arthralgia, headache, unrefreshing sleep, post-exertional malaise (lasting >24 hours), and/or orthostatic intolerance​

                              Exam

                              tender lymphadenopathy, muscle pain, and other non-specific signs

                              1st investigation
                              • none:

                                diagnosis is based on history, and clinical signs and symptoms

                                More
                              Other investigations

                                Chronic idiopathic fatigue

                                History

                                fatigue lasting more than 6 months, does not meet criteria for chronic fatigue syndrome

                                Exam

                                tender lymph nodes, muscle pain, and other non-specific signs

                                1st investigation
                                • none:

                                  diagnosis is clinical

                                Other investigations

                                  Heavy metal toxicity

                                  History

                                  history of metal-on-metal hip implant (cobalt or chrome toxicity); dental amalgams, excess fish consumption (mercury toxicity); exposure to very old paints, glass artisans, battery production, use of Ayurvedic medicines (lead toxicity); paraesthesias, blurred vision, psychiatric changes, cognitive decline

                                  Exam

                                  tremor, ataxia

                                  1st investigation
                                  • serum level (lead, mercury, cobalt, chrome):

                                    elevated

                                  Other investigations

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