Differentials
Common
Lung cancer
History
cough, shortness of breath, smoking history, asbestos exposure, hemoptysis, chest pain, wheezing; with spread into the neck, may have features of superior vena cava syndrome (facial plethora and distended neck veins when arms raised above the head) or even hoarseness
Exam
weight loss, respiratory distress common; may be absent or decreased breath sounds, dullness to percussion, mediastinal shift; other signs depend on spread and type of tumor
1st investigation
Bronchiectasis
History
history of recurrent respiratory tract infections; cough producing large amounts of mucopurulent sputum, diurnal variation (e.g., worse in the morning), positional worsening; dyspnea, wheezing, hemoptysis
Exam
crackles and wheezes, predominantly over lower lobes
1st investigation
- CXR:
thickening of bronchi and bronchioles, seen as ill-defined perihilar linear densities associated with indistinctness of central pulmonary artery margins
More - high-resolution CT scan chest:
bronchial dilation (internal bronchial diameter greater than diameter of accompanying bronchial artery, known as signet ring formation) and lack of bronchial tapering on sequential slices
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Other investigations
- spirometry:
irreversible obstructive defect, with FEV₁:forced vital capacity ratio <70%
Lung abscess
History
presence of risk factors (immunosuppression, poor oral hygiene, drug misuse, alcohol misuse, seizure disorder, stroke, lung cancer); cough with purulent sputum and foul odor, fever, chills and sweats, pleuritic chest pain, possibly hemoptysis
Exam
tachypnea, fever, dyspnea, dullness to percussion, whispered pectoriloquy and bronchophony on auscultation
1st investigation
- CXR:
cavitary lesion with air fluid level, usually in posterior segment of right upper lobe
- CBC:
leukocytosis
- blood culture:
positive for infectious organism
Other investigations
- chest CT:
localizes position and size of collection
- bronchoscopy:
localizes position and size of collection
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Empyema
History
recent pneumonia, fever, cough, purulent sputum production, chest pain
Exam
febrile, toxic patient, dullness on percussion, absence of breath sounds over affected area
1st investigation
Congenital heart disease
History
poor feeding in infants, faltering growth, shortness of breath, diaphoresis, irritability, recurrent lung infections; adults who survive have symptoms of heart failure (dyspnea, peripheral edema, fatigue) or differential cyanosis (pink upper extremities and cyanotic lower extremities as can occur in coarctation of the aorta)
Exam
various; cardiac murmur, central cyanosis, dyspnea, failure to thrive
1st investigation
Other investigations
- cardiac catheterization:
pulmonary stenosis and ventricular septal defects may be seen on angiogram; provides hemodynamic data such as systemic right ventricular pressure and right-to-left shunt
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Infective endocarditis
History
fever, fatigue, chills, anorexia, night sweats, myalgia, and/or arthralgia
Exam
majority febrile, new or changing heart murmur, petechiae on mucosae and extremities, splinter hemorrhages below nails, Osler nodes on digits, Janeway lesions, hepatosplenomegaly
1st investigation
Other investigations
Hypersensitivity pneumonitis (extrinsic allergic alveolitis)
History
exposure to nonhuman protein or chemicals such as epoxy resins, shortness of breath, nonproductive or productive cough, fever, malaise, weight loss, bibasilar or diffuse rales
Exam
dyspnea, cough, febrile, malaise, weight loss, bibasilar or diffuse rales on auscultation
1st investigation
- immunologic response to causative antigen:
antibody to the putative antigen positively identified through immunologic blood test
- CBC:
leukocytosis; normocytic, normochromic anemia
- erythrocyte sedimentation rate:
elevated
- albumin:
low
- CXR:
patchy, nodular infiltrates are observed in acute and subacute hypersensitivity pneumonitis; fibrosis in chronic hypersensitivity pneumonitis
- high-resolution CT scan chest:
ground-glass shadowing/attenuation and poorly defined micronodules; features of chronic hypersensitivity pneumonitis include mosaic attenuation, centrilobular nodules, and relative basal sparing
- diffusing lung capacity of carbon monoxide:
decreased
Other investigations
- pulmonary function tests:
restricted pattern in acute hypersensitivity pneumonitis; mixed restrictive and obstructive features in subacute or chronic hypersensitivity pneumonitis
- bronchoalveolar lavage:
positive antibody and lymphocytosis (elevated CD8+ cells)
- lung biopsy:
bronchocentric infiltrate consisting of lymphocytes, plasma cells, neutrophils, foamy macrophages, and noncaseating granulomas; in later stages interstitial fibrosis predominates
Uncommon
Cystic fibrosis
History
variable; mainly presents in infancy or childhood; chronic cough, sputum production, persistent chest symptoms, wheezing; failure to thrive, diarrhea, abdominal pain, prolonged neonatal jaundice; infertility due to azoospermia
Exam
variable; rhinitis, nasal polyps, tachypnea, respiratory distress, wheeze, cough, hyperresonance on chest percussion; abdominal distention, organomegaly, rectal prolapse, signs of malabsorption (failure to thrive, abdominal tenderness, steatorrhea), salivary gland swelling, and/or scoliosis may also be present
1st investigation
- sweat test:
increased chloride in sweat; >60 mEq/L is diagnostic
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Other investigations
- gene analysis:
mutations in the CFTR gene
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Interstitial pulmonary fibrosis
History
smoking history, progressive exertional dyspnea, chronic cough (occasionally productive), hemoptysis, fatigue, weakness, weight loss
Exam
tachypnea, end-expiratory rales at the bases, wheezing; pulmonary hypertension and right heart failure occurs in severe disease
1st investigation
Other investigations
- spirometry:
restrictive pattern with low forced vital capacity (FVC) and normal or increased FEV₁:FVC ratio
- lung biopsy:
variable
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Sarcoidosis
History
chronic cough, dyspnea; usually extrapulmonary symptoms: arthralgia, eye pain, blurred vision, painful skin lesions
Exam
variable; lymphadenopathy, wheezing, rhonchi, uveitis, arthritis or periarthritis, organomegaly, painful skin papules or nodules, erythema nodosum
1st investigation
Other investigations
- biopsy from viscera:
noncaseating granuloma
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Asbestosis
History
history of prolonged asbestos exposure; progressive dyspnea; dry cough with chest discomfort
Exam
rales, described as cellophane or velcro rales, initially heard in end-inspiratory phase
1st investigation
Other investigations
- tissue biopsy via bronchoscopy:
asbestos bodies
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Pleural mesothelioma
History
history of asbestos exposure; older adult patient; recent-onset shortness of breath and nonpleuritic chest pain; cough, weight loss, weakness may also occur
Exam
dullness on percussion, absence of breath sounds over affected area
1st investigation
Other investigations
- chest MRI:
degree of tumor extension, especially to the chest wall and diaphragm
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Cavitating pulmonary tuberculosis (TB)
History
fever, chills, chronic cough, weight loss, night sweats; history of travel to endemic areas, HIV infection, or immunosuppression
Exam
variety of chest signs, depends on severity of lung involvement: may include tachypnea, decreased breath sounds, crackles, dullness to percussion
1st investigation
- CXR:
miliary mottling, cavitary and/or apical fibrocavitary changes. 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 - nucleic acid amplification tests (NAAT):
positive for M tuberculosis
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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
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Pulmonary metastases
History
symptoms may be absent in multiple metastases; dyspnea common; sudden-onset dyspnea indicates hemorrhage or pneumothorax; wheezing or hemoptysis suggests endobronchial metastases; extension to pleura may cause pleuritic chest pain; patients may have paresthesias (due to associated hypercalcemia, paraproteinemia, or vasculitis)
Exam
dyspnea, wheezing, respiratory distress
1st investigation
- CXR:
nodules or infiltration
Atrial myxoma
History
dyspnea, paroxysmal nocturnal dyspnea, fatigue, dizziness, syncope, fever, weight loss, hemoptysis, sudden death (due to embolization anywhere in arterial system)
Exam
raised jugular venous pressure, loud first heart sound, delayed pulmonic component of the second heart sound, tumor plop (early diastolic sound), fever, cyanosis, rash, petechiae
1st investigation
Other investigations
- cardiac catheterization:
variable
More - biopsy:
gelatinous growth with nests of spindle cells
Axillary artery aneurysm
History
usually sudden onset; coolness and numbness of affected hand, weakness and heaviness in affected arm, symptoms worsen on exercise
Exam
unilateral clubbing, pallor, coolness of affected arm and hand, slow capillary refill, peripheral pulses in affected arm and hand may be normal
1st investigation
- Doppler ultrasonography:
turbulent, pulsatile flow within the structure, contiguous with brachial artery distally
Other investigations
- CT arteriography:
exact level of bifurcation and extent of aneurysm demonstrated
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Brachial arteriovenous malformations
History
limb hypertrophy if chronic, discoloration of affected limb
Exam
unilateral clubbing, soft boggy swelling on affected limb, bruit heard over swelling, partially compressible
1st investigation
- Doppler ultrasonography:
vascular anomalous flow
Thyroid acropachy
History
history of autoimmune thyrotoxicosis (usually Graves disease, but may be present in Hashimoto thyroiditis); symptoms of thyrotoxicosis (heat intolerance, sweating, weight loss, palpitations, scalp hair loss, irritability)
Exam
soft-tissue swelling of hands and feet, signs of thyrotoxicosis (exophthalmos, pretibial myxedema, goiter, tachycardia, tremor)
1st investigation
- thyroid-stimulating hormone (TSH):
suppressed
- serum free T4:
elevated
Other investigations
- serum free or total T3:
elevated
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Acromegaly
History
headache, snoring, visual field defects, hyperhidrosis, coarsening of facial features, joint pain and dysfunction, fatigue, increased appetite, polyuria/polydipsia
Exam
acromegalic facies (frontal bossing, thickening of nose, prognathism, macroglossia), hirsutism, oily skin, enlarged hands with sausage-shaped fingers, organomegaly, hypertension, arrhythmias, thyroid anomalies, arthritis
1st investigation
Severe secondary hyperparathyroidism
History
bone and joint pain, muscle weakness, history of renal disease
Exam
myopathy, osteomalacia, xerosis
1st investigation
- serum parathyroid hormone levels:
elevated
More - serum calcium:
reduced or normal
- vitamin D levels:
reduced
Other investigations
Hodgkin lymphoma
History
may be asymptomatic; fever, chills, night sweats, weight loss, chest pain, cough, dyspnea, pruritus, bone pains
Exam
rubbery lymph nodes in neck, axillae, and inguinals; hepatosplenomegaly, Waldeyer ring involvement (tonsils, nasopharynx, base of tongue)
1st investigation
Disseminated chronic myeloid leukemia
History
fatigue, anorexia, weight loss, abnormal bleeding or bruising; left shoulder pain (indicates splenic infarction or perisplenitis)
Exam
pallor, plethora, abdominal distention due to splenomegaly, bruising; occasionally tender purple papules on the body accompanied by fever (Sweet syndrome)
1st investigation
- CBC:
elevated WBC, anemia, thrombocytosis
- peripheral blood smear:
mature or maturing myeloid cells, elevated basophils and eosinophils
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Ulcerative colitis
History
age 15-45 years, bloody diarrhea, abdominal pain, and bloating
Exam
abdominal tenderness and distention, extraintestinal manifestations including peripheral arthritis, sacroiliitis, pyoderma gangrenosum, erythema nodosum
1st investigation
- colonoscopy and biopsy:
continuous uniform inflammation that always involves the rectum; normal terminal ileum (or mild "backwash" ileitis in pancolitis)
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Other investigations
- CBC:
microcytic anemia, thrombocytosis
- erythrocyte sedimentation rate:
elevated
- autoantibodies:
negative anti-Saccharomyces cerevisiae antibody and positive perinuclear antineutrophil cytoplasmic antibody
Crohn disease
History
crampy abdominal pain, intermittent diarrhea, bloody diarrhea if colitis a feature, weight loss, fatigue
Exam
aphthous ulcers, evidence of weight loss, pallor, abdominal tenderness, abdominal mass, perianal fistula, perirectal abscess, anal fissure, perianal skin tags; extraintestinal manifestations including iritis, arthritis, sacroiliitis, erythema nodosum, pyoderma gangrenosum
1st investigation
- upper gastrointestinal and small-bowel series:
thickening and distortion of valvulae conniventes due to edema and ulceration
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Other investigations
- colonoscopy and biopsy:
aphthous ulcers, mucosal edema, cobblestoning, luminal narrowing; discontinuous, with intermittent areas of normal-appearing bowel (skip lesions)
More - CBC:
anemia; leukocytosis
More - erythrocyte sedimentation rate:
elevated
- autoantibodies:
positive anti-Saccharomyces cerevisiae antibody and negative perinuclear antineutrophil cytoplasmic antibody
Primary biliary cholangitis
History
middle-aged women, personal or family history of autoimmune disease or primary biliary cholangitis, history of hypercholesterolemia, pruritus, fatigue, sleep disturbance, dry eyes and mouth (sicca syndrome), postural dizziness/blackouts, right upper quadrant discomfort
Exam
hepatomegaly, skin hyperpigmentation, splenomegaly, jaundice, xanthelasmata
1st investigation
- LFTs:
elevated bilirubin, gamma glutamyl transferase, and alk phos
- antimitochondrial antibodies:
present
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Other investigations
Cirrhosis
History
presence of risk factors (alcohol misuse, intravenous drug use, unprotected intercourse, obesity, blood transfusion); may be asymptomatic or have nonspecific constitutional symptoms such as fatigue, weakness, weight loss
Exam
jaundice, hepatomegaly, nodularity of liver on palpation, ascites, signs of end-stage liver failure
1st investigation
- LFTs:
deranged
More - albumin:
reduced
- prothrombin time:
prolonged
More - abdominal ultrasound:
early stages: enlarged smooth liver; subsequently: coarse echotexture; advanced disease: small liver with surface nodularity, ascites, splenomegaly, increased diameter of portal vein (≥13 mm) or collateral vessels
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Other investigations
- liver biopsy:
architectural distortion of liver parenchyma with formation of regenerative nodules
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Thyroid cancer
History
most commonly affects women; painless palpable solitary thyroid nodule; hoarseness or dysphagia may occur if recurrent laryngeal nerve involved or vocal cord compressed; history of head and neck irradiation
Exam
palpable thyroid nodule (particularly if hard and fixed), cervical lymphadenopathy
1st investigation
- thyroid ultrasonography:
detects cysts and structure of thyroid mass
- fine needle aspiration (FNA) biopsy:
cytology confirms malignant features
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Other investigations
Thymus cancer
History
history of myasthenia gravis, fatigue, generalized weakness, weight loss, persistent cough, chest pain, dyspnea common early symptoms; one third of patients are asymptomatic at time of diagnosis
Exam
dyspnea, loss of weight; rarely produces clubbing (usually present when associated with hypertrophic osteoarthropathy)
1st investigation
Other investigations
- chest PET scan:
reveals a hypermetabolic mass
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Lipoid pneumonia
History
history of mineral oil (e.g., in laxatives) or vegetable oil ingestion; history of lung cancer or bronchiolitis obliterans, recent chemotherapy or radiation therapy; may be asymptomatic or present with nonspecific symptoms (cough, chest pain, dyspnea)
Exam
variable and nonspecific signs including fever, tachypnea, crackles
1st investigation
- CXR:
alveolar infiltrates, consolidation
Pulmonary artery sarcoma
History
dyspnea, chest and/or back pain, cough, hemoptysis, weight loss, malaise, syncope, fever, rarely sudden death
Exam
systolic ejection murmur, cyanosis, extremity edema, jugular vein distention, hepatomegaly
1st investigation
- CXR:
solid sarcomatous expansions of proximal pulmonary artery are highly suggestive, especially if there are pulmonary nodules; decreased vascularity, and cardiac enlargement
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Other investigations
- chest CT:
nonspecific uniform mass consistent with organized thrombi
More - intravascular ultrasonography:
unique echogenic mass with irregular surface, string-shaped projection, mosaic pattern containing flecked echolucent and increased echogenic areas
More - PET scan chest:
shows heterogeneous soft-tissue density from areas of necrosis, hemorrhage, and ossification
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Ulcerative esophagitis
History
burning retrosternal pain, nausea, vomiting
Exam
minimal findings, occasional epigastric tenderness
1st investigation
- barium studies:
ulceration seen in barium shadow
- endoscopy:
direct visualization of ulceration
Other investigations
- biopsy:
epithelial hyperplasia, infiltration by inflammatory cells, and sometimes focal necrosis possible in early lesions; presence of intraepithelial eosinophils common
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Achalasia
History
dysphagia, regurgitation, chest pain, heartburn
Exam
weight loss
1st investigation
- barium studies:
dilated esophagus, contrast passes slowly into stomach, distal esophagus narrowed and resembles a bird's beak
- esophageal manometry:
incomplete relaxation of lower esophageal sphincter in response to swallowing; high resting pressure of lower esophageal sphincter; absent esophageal peristalsis
Other investigations
Celiac disease
History
diarrhea, flatulence, steatorrhea, weight loss, weakness, fatigue; abdominal pain not common in uncomplicated cases; extraintestinal symptoms may be present (dermatitis herpetiformis, history of bone pain, or previous fracture suggesting osteoporosis)
Exam
protuberant abdomen (may be tympanic due to bowel distention); pallor, easy bruising, aphthous stomatitis
1st investigation
Tropical sprue
History
prolonged exposure to an endemic area; diarrhea, fever, fatigue, malaise, anorexia
Exam
glossitis, stomatitis, weight loss, dehydration, pallor, pedal edema
1st investigation
Other investigations
Leiomyoma of the esophagus
History
young patients, dysphagia, retrosternal discomfort, chest pain, regurgitation; bleeding is rare
Exam
weight loss and wasting in severe cases
1st investigation
- barium studies:
smooth concave mass underlying intact mucosa, encroaching lumen of esophagus
Familial clubbing
History
positive family history; absence of symptoms suggesting an underlying organic condition
Exam
absence of signs suggesting an underlying organic condition
1st investigation
- none:
diagnosis is clinical
Other investigations
Pachydermoperiostosis (primary hypertrophic osteoarthropathy)
History
onset often at puberty; excessive sweating, acne, arthralgia, coarsening of facial features, enlargement of fingers and toes, cutaneous thickening, and furrowing of scalp
Exam
combination of pachydermia (elephant-like skin), periostosis (swelling around the joints, especially wrists and knees), and clubbing is typical; possibly also seborrhea, acne, hyperhidrosis, cutis verticis gyrata (thickened skin of the scalp manifesting as folds and furrows), hemarthrosis or hydrarthrosis
1st investigation
- CXR:
usually normal
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Other investigations
- plain film radiographs:
x-ray of the hands shows acro-osteolysis of the terminal phalanges; films of other joints show periosteal reactions
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Secondary hypertrophic osteoarthropathy
History
painful joints with limited range of movement; pulmonary, hepatic, or endocrine symptoms
Exam
enlarged extremities due to periarticular and osseous proliferation, tender and swollen joints; signs suggesting underlying cause (lung cancer, abscess, bronchiectasis, emphysema, Hodgkin lymphoma, metastatic disease, cystic fibrosis, cirrhosis, inflammatory bowel disease, biliary atresia)
1st investigation
Other investigations
- chest CT scan:
delineates the nature of pulmonary involvement (if present)
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Palmoplantar keratoderma
History
thickening of palms and soles; may be hereditary but more commonly acquired
Exam
hyperkeratosis
1st investigation
- none:
diagnosis is clinical
Other investigations
Pregnancy
History
amenorrhea, nausea, vomiting, weight gain
Exam
breast enlargement, abdominal distention, palpation of abdominal or uterine mass
1st investigation
- urine beta-hCG:
positive
Other investigations
- pelvic ultrasound:
visualization of fetal parts
Pseudoclubbing
History
asymptomatic
Exam
Lovibond angle between 160° and 180°; clubbing may be localized to a single digit; subungual tumor, cyst, or osteoid osteoma may be present; if clubbing is generalized acro-osteolysis (loss of terminal tufts of digits) may be present
1st investigation
- none:
diagnosis is clinical
Other investigations
Myelofibrosis
History
may be a history of exposure to radiation or industrial chemicals; nonspecific symptoms are common (e.g., weight loss, low-grade fever and night sweats, fatigue, anorexia, pruritus); gastrointestinal bleeding, hemoptysis, hematuria, ascites, and pericardial effusion may be present
Exam
splenomegaly with or without hepatomegaly, progressive dyspnea, cutaneous petechiae
1st investigation
- CBC with differential:
anemia
- peripheral blood smear:
teardrop-shaped red blood cells (RBCs), presence of metamyelocytes, myelocytes, promyelocytes, myeloblasts, and nucleated RBCs in the circulation
- bone marrow aspiration:
may be “dry”
- bone marrow biopsy:
fibrosis
Other investigations
- JAK2 V617F mutation:
positive in >50% of patients
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