28 HOW TO TREAT : SARCOIDOSIS
28 HOW TO TREAT : SARCOIDOSIS
19 APRIL 2024 ausdoc . com . au a combination of medications , hydration and lifestyle changes . First-line treatment depends on the severity of the hypercalcaemia ; it often includes increased hydration ( oral / IV ) and cessation of medication that contributes to hypercalcaemia , such as vitamin D supplements . In practice , corticosteroids may be used to reduce inflammation and suppress the overproduction of calcitriol . It is important to recognise that 80-90 % of presentations of hypercalcaemia are accounted for by hyperparathyroidism and malignancy . 10 Thus , assessment with a parathyroid hormone level , renal function and appropriate malignancy screening is important even in patients with known sarcoidosis . Hypercalciuria ( excess urinary calcium ) may lead to the development of renal calculi and subsequent obstructive renal failure . In the authors ’ experience , recommendation for appropriate hydration and avoidance of contributory medications is sufficient first-line advice while remission is being sought .
MAKING THE DIAGNOSIS
A DIAGNOSIS of sarcoidosis requires a combination of clinical , radiological and cytological or histopathological findings ( see box 2 ). The diagnosis requires a compatible clinical presentation of sarcoidosis accompanied by the presence of non-necrotising ( non-caseating ) granuloma on biopsy . Other causes of granulomatous disease must also be excluded as granulomas are non-specific for sarcoidosis . 11 Box 3 lists the causes of granulomatous disease .
Classically , biopsy was avoided in circumstances of lupus perino , Löfgren syndrome , Heerfordt syndrome or in patients with asymptomatic hilar lymphadenopathy . However , with the advent of EBUS , biopsy can be performed safely and efficiently on those with asymptomatic hilar lymphadenopathy allowing for the exclusion of other pathologies . The authors recommend referral of all patients with asymptomatic lymphadenopathy to a respiratory physician to discuss the role of diagnostic evaluation ( see box 4 ).
The role of chest imaging
Imaging of the chest plays an essential role in the diagnosis and understanding of organ involvement in sarcoidosis . Typical findings on plain chest X-ray range from normal to bilateral hilar enlargement to parenchymal fibrosis . However , in the era of CT scanning and less invasive biopsy methods ( that is , EBUS ), chest X-ray for sarcoidosis diagnosis has been superseded , although it remains a useful tool for monitoring established stable disease . 12 For incidentally detected symmetrical hilar enlargement on chest X-ray , the authors recommend a CT chest with contrast as the initial screening modality to assess for features of sarcoidosis , malignancy or other causes . Contrast in this setting is helpful to differentiate vessels from lymph nodes . When only evidence of interstitial lung disease is seen ( that may be subtle on chest X-ray ), a high-resolution CT protocol scan is more appropriate as the parenchyma is better visualised ( see figures 3 and 4 ). If both features are present , a discussion with the local radiology service is important as most can perform both CT protocols ( high-resolution CT and contrast CT ) simultaneously . A broad range of imaging modalities are
Table 1 . Sarcoidosis presentations in various organ systems Organ system Lungs Skin Nervous system
Heart Ocular Joint Liver Spleen Endocrine Systemic
T-1 cells
Resolution
Presentation
increasingly utilised in the evaluation of sarcoidosis . These may include fluorodeoxyglucose ( FDG )– PET to discern sites for biopsy , as well as cardiac MRI to evaluate the presence of cardiac sarcoidosis .
Asymptomatic bilateral hilar lymphadenopathy
The incidental finding of asymptomatic mediastinal / hilar lymphadenopathy is an anxiety-provoking
Intrathoracic lymphadenopathy , pulmonary fibrosis , chronic cough Lupus perino , erythema nodosum
Optic neuritis , meningitis , seizures , cranial neuropathy , myelopathy , small fibre neuropathy , central parenchymal lesions
Heart block / arrythmia , heart failure with preserved ejection fraction Uveitis Synovitis Alkaline phosphatase elevation , cirrhosis / fibrosis Splenomegaly Hypercalcaemia
Unknown sarcoid antigen
Increased T-1 response
Increased T-2 response
Fatigue , fever , Löfgren syndrome , Heerfordt syndrome
situation for both patient and clinician . While approximately 50 % of isolated mediastinal / hilar lymphadenopathy is thought to be reactive , the differential diagnoses include malignancy ( haematological / solid organ ), TB , sarcoidosis , occupational lung disease , connective tissue diseases and amyloidosis . 13 Unfortunately , there is a paucity of evidence to guide clinical decision-making in this situation . In general terms , asymptomatic
HLA-DRB1 , HLA-DBQ1 , HLA-B * 8 , BTNL2
TNF-α , IL-12 , IL-1 , IL-6 , IL-15 , IL-18 , IL-27 , GM-CSF , MCP-1 , RANTES
T-1 cytokines IFN- γ , IL-2
T-cell
CD4 + T-cell
Granuloma
APC
T-2 cytokines IL-4 , IL-5 , IL-10 , IL-13
Granulomaderived factors : ACE , TNF-α , neopterin , TGF-β , IL-6 , osteopontin
Fibrosis
T-2 cells
Figure 1 . Sarcoid immunopathogenesis . ACE , GM-CSF ( granulocyte – macrophage colony-stimulating factor ), HLA ( human leucocyte antigen ), IFN ( interferon ), IL ( interleukin ), MCP ( monocyte chemo-attractant protein ), MIP ( macrophage inflammatory protein ), RANTES ( regulated on activation normal T-cell expressed and secreted ), TGF ( transforming growth factor ), TH ( T helper ).
Diagram from Ahmadzai H et al and reproduced with permission . Based on Ahmadzai H et al 2018 6 mediastinal lymph nodes less than 10mm in the short axis are likely to be benign . 14
The authors recommend a cut-off of 10mm for normal nodes and consideration of referral to a respiratory physician or , at a minimum , surveillance of mediastinal or hilar lymph nodes be undertaken for nodes greater than this size ( see figure 5 ). Where a clinical picture of sarcoidosis is strong , serial imaging may be undertaken ,
Box 1 . Sarcoidosis syndromes
Löfgren syndrome
• Bilateral hilar lymph node enlargement .
• Erythema nodosum .
• Fever .
• Migratory polyarthritis .
Heerfordt syndrome
• Uveitis .
• Parotitis .
• Fever .
Box 2 . Diagnostic criteria
• Compatible clinical presentation .
• Non-necrotising granuloma on tissue sampling .
• Exclusion of other causes of granulomatous disease .
Box 3 . Causes of granulomatous disease
• Sarcoidosis .
• TB ( active and latent ).
• Foreign body .
• Malignancy / sarcoidosis-like reaction to tumour .
• Non-tuberculous mycobacterium .
• Inflammatory bowel disease ( for example , Crohn ’ s disease ).
• Autoimmune ( eosinophilic granulomatosis with polyangiitis , granulomatosis with polyangiitis , SLE , immunoglobulin G4-related disease ).
• Drugs ( immune checkpoint inhibitors , antiretrovirals , TNFa inhibitors , BCG ).
• Hypersensitivity pneumonitis ( berylliosis , hot tub lung ) and Langerhans cell histiocytosis .
Box 4 . Initial evaluation in sarcoidosis
• History ( occupational and environmental exposure , symptoms ).
• Physical examination .
• Posteroanterior chest X-ray .
• Pulmonary function tests .
• FBC .
• Serum chemistries : EUC , calcium , LFTs .
• Urinary assessemnt for calcium excretion .
• ECG .
• Routine ophthalmological examination .
• TB screening : interferon-gamma release assay / tuberculin skin test .
although frequently , endobronchial ultrasound-guided biopsy up front is undertaken to strengthen a sarcoidosis diagnosis while simultaneously excluding more sinister pathology and alleviating anxiety . The radiological characteristics for the stages of sarcoidosis appear in table 2 .
Bronchoscopy , endobronchial ultrasound and transbronchial needle aspiration
The presence of non-necrotising granulomatous inflammation from involved sites strongly supports , although is not diagnostic of , sarcoidosis . The availability of EBUS has revolutionised the diagnosis of