Sarcoidosis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief:

Overview

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Differential Diagnosis

Sarcoidosis has many differentials, which can be classified depending on the organ involved.[1]

Lung[2]

1.Tuberculosis 2.Atypical Mycobacteriosis 3.Cryptococcosis 4.Aspergillosis 5.Aspiration of foriegn materials 6.Blastomycosis 7.Pneumocystitis carinii 8.Pneumoconiosis 9.Drug reactions 10.Hypersensitivity pneumonitis 11.Drug reactions12..Histoplasmosis 13.Chronic interstitial pneumonia 14.Necrotizing sarcoid granulomatosis 15.Wegner's granulomatosis

Lymph Node

1.Tuberculosis 2.Atypical Mycobacteriosis 3.Brucellosis 4.GLUS syndrome 5.Cat scratch disease 6.Toxoplasmosis 7.Hodgkin disease 8.Non Hodgkin lymphoma 9.Sarcoid reaction in lymph nodes to carcinoma 10.Kikuchi disease(granulomatous histiocytic necrotizing lymphadenitis)

Skin

1.Tuberculosis 2.Atypical mycobacteriosis 3.Fungal infection 4.Rheumatoid nodules 6.Reaction to foreign bodies

Liver

1.Tuberculosis 2.Brucellosis 3.Schitosomiasis 4.Crohn's disease 5.Hodgkin's disease 6. Non hodgkin's lymphoma 7.GLUS syndrome 8.Primary biliary cirrhosis

Bone Marrow

1.Tuberculosis 2.Histoplasmosis 3.Cytomegalovirus 4.Drugs 5.Infectious Mononucleosis 6.GLUS syndrome 7.Hodgkin's disease 8.Non Hodgkin's lymphoma

Other biopsy sites

1.Tuberculosis 2.Brucellosis 3.Crohn's disease 4.GLUS Syndrome 5.Other infections 6.Giant cell myocarditis

Differential diagnosis

Causes of

lung cavities

Differentiating Features Differentiating radiological findings Diagnosis

confirmation

  • CXR and CT demonstrates cavities in the upper lobe of the lung
  • Sputum smear positive for acid-fast bacilli and nucleic acid amplification tests (NAAT) is used on sputum or any sterile fluid for rapid diagnosis and is positive for mycobacteria.
  • Any age group
  • Acute, fulminant life threating complication of prior infection
  • >100.4F fever, with hemodynamic instability
  • Worsening pneumonia-like symptoms
  • CBC is positive for causative organism
  • Children and elderly are at risk
  • Empyema appears lenticular in shape and has a thin wall with smooth luminal margins
  • Pulmonary nodules with cavities and infiltrates are a frequent manifestation on CXR
  • Elderly females of 40-50 age group
  • Manifestation of rheumatoid arthritis
  • Presents with other systemic symptoms including symmetric arthritis of the small joints of the hands and feet with morning stiffness are common manifestations.
  • Pulmonary nodules with cavitation are located in the upper lobe (Caplan syndrome) on Xray.
  • On CXR bilateral adenopathy and coarse reticular opacities are seen.
  • CT of the chest demonstrates extensive hilar and mediastinal adenopathy
  • Additional findings on CT include fibrosis (honeycomb, linear, or associated with bronchial distortion), pleural thickening, and ground-glass opacities.[9]
  • Common appearance on CT is patchy consolidation,often accompanied by ground-glass opacities and nodules.[13]
  • Exclusively afflicts smokers, with a peak age of onset of between 20 and 40 years.
  • Clinical presentation varies, but symptoms generally include months of dry cough, fever, night sweats and weight loss.
  • Skin is involved in 80% of the cases, scaly erythematous rash is typical.
  • Thin-walled cystic cavities are the usual radiographic manifestation, observed in over 50% of patients by either CXR or CT scans.[15]
  • Biopsy of the lung

Sarcoidosis must be differentiated from other diseases that cause bone pain, edema, and erythema.

Disease Findings
Soft tissue infection
(Commonly cellulitis)
History of skin warmness, swelling and erythema. Bone probing is the definite way to differentiate them.[16][17]
Osteonecrosis
(Avascular necrosis of bone)
Previous history of trauma, radiation, use of steroids or biphosphonates are suggestive to differentiate osteonecrosis from ostemyelitis.[18][19]
MRI is diagnostic.[20][21]
Charcot joint Patients with Charcot joint commonly develop skin ulcerations that can in turn lead to secondary osteomyelitis.
Contrast-enhanced MRI may be diagnostically useful if it shows a sinus tract, replacement of soft tissue fat, a fluid collection, or extensive marrow abnormalities. Bone biopsy is the definitive diagnostic modality.[22]
Bone tumors May present with local pain and radiographic changes consistent with osteomyelitis.
Tumors most likely to mimic osteomyelitis are osteoid osteomas and chondroblastomas that produce small, round, radiolucent lesions on radiographs.[23]
Gout Gout presents with joint pain and swelling. Joint aspiration and crystals in synovial fluid is diagnostic for gout.[24]
SAPHO syndrome
(Synovitis, acne, pustulosis, hyperostosis, and osteitis)
SAPHO syndrome consists of a wide spectrum of neutrophilic dermatosis associated with aseptic osteoarticular lesions.
It can mimic osteomyelitis in patients who lack the characteristic findings of pustulosis and synovitis.
The diagnosis is established via clinical manifestations; bone culture is sterile in the setting of osteitis.
Sarcoidosis It involves most frequently the pulmonary parenchyma and mediastinal lymph nodes, but any organ system can be affected.
Bone involvement is often bilateral and bones commonly affected include the middle and distal phalanges (producing “sausage finger”), wrist, skull, vertebral column, and long bones.
Langerhans' cell histiocytosis The disease usually manifests in the skeleton and solitary bone lesions are encountered twice as often as multiple bone lesions.
The tumours can develop in any bone, but most commonly originate in the skull and jaw, followed by vertebral bodies, ribs, pelvis, and long bones.[25]

must be differentiated from other causes of hypercalcaemia

Differential diagnosis of hyperparathyroidism on the basis of hypercalcemia
Disorder Mechanism of hypercalcemia Clinical features Laboratory findings Imaging & diagnostic modalities
PTH Calcium Phosphate Other findings
Hyperparathyroidism Primary hyperparathyroidism Increase in secretion of parathyroid hormone (PTH) from a primary process in parathyroid gland. Parathyroid hormone causes increase in serum calcium.
  • Usually asymptomatic
  • Hypercalcemia detected on routine biochemical panel
↓/Normal Normal/↑ calcitriol Findings of bone resorption:

Preoperative localization of hyperfunctioning parathyroid gland:

Predicting post-operative success:

Secondary hyperparathyroidism Increase in secretion of parathyroid hormone (PTH) from a secondary process. Parathyroid hormone causes increase in serum calcium after long periods. ↓/Normal --
Tertiary hyperparathyroidism Continuous elevation of parathyroid hormone (PTH) even after successful treatment of the secondary cause of elevated parathyroid hormone. Parathyroid hormone causes increase in serum calcium. --
Familial hypocalciuric hypercalcemia This is a genetic disorder caused my mutation in calcium-sensing receptor gene.
  • A benign condition
  • Does not require treatment
Normal/↑ Normal/↑ -- --
  • Urinary calcium/creatinine clearance ratio
Malignancy[26] Humoral hypercalcemia of malignancy[27][28][29] Tumor cells secretes parathyroid hormone-related protein (PTHrP) which has similar action as parathyroid hormone. -- ↓/Normal PTHrP

Normal/↑ calcitriol

Osteolytic tumors Multiple myeloma produces osteolysis of bones causing hypercalcemia. Osteolytic metasteses can cause bone resorption causing hypercalcemia. -- --
Production of calcitirol Some tumors has ectopic activity of 1-alpha-hydroxylase leading to increased production of calcitriol. Calcitriol is active form of vitamin D and causes hypercalcemia. -- -- Calcitriol
Ectopic parathyroid hormone[30] Some tumors leads to ectopic production of parathyroid hormone. ↓/Normal Normal/↑ calcitriol
Medication induced Lithium[31] Lithium lowers urinary calcium and causes hypercalcemia. Lithium has been reported to cause an increase in parathyroid hormone and enlargement if parathyroid gland after weeks to months of therapy. -- --
Thiazide diuretics Thiazide diuretics lowers urinary calcium excretion and causes hypercalcemia. -- -- -- --
Nutritional Milk-alkali syndrome Hypercalcemia is be caused by high intake of calcium carbonate. -- -- --
Vitamin D toxicity Excess vitamin D causes increased absorption of calcium from intestine causing hypercalcemia. -- -- Vitamin D (calcidiol and/or calcitriol) --
Granulomatous disease Sarcoidosis[34] Hypercalcemia is causes by endogeous production of calcitriol by disease-activated macrophages. -- -- Calcitriol

ACE levels

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