Sarcoidosis Flashcards
Introduction
Multisystem granulomatous disease of unknown aetiology
Mainly skin, eyes, lungs, mediastinal and peripheral lymph nodes
Skin lesions may be disfiguring —> strong psychosocial impact
One of the great imitators - variable cutaneous manifestations
Specific (histopathologically display sarcoidosis granulomas) vs non-specific lesions
Women > men
African Americans/Indians - more severe and chronic disease
Caucasians - asymptomatic disease, Lofgren syndrome
Associated diseases
Increased risk of lymphoproliferative disease I.e. Hodgkin lymphoma
Concomitant autoimmune disease _
- Sjogren syndrome
- systemic sclerosis
- RA
- vasculitis
- psoriasis
- autoimmune chronic hepatitis
- primary biliary cirrhosis
- autoimmune thyroid disease esp Graves disease
Systemic manifestations
Lung
Extrapulmonary -
- Eye
- Reticuloendothelial (lymph nodes, spleen, bone marrow)
- Liver
- MSK
- Heart
- Other I.e. upper respiratory tract, parotid, hypercalcaemia/hypercalciuria, renal, GI, genital, endocrine
Acute/subacute (weeks/few months) vs insidious onset (several months)
Acute/subacute = good prognosis, Mild constitutional symptoms -
- Fatigue
- Malaise
- Anorexia
- Weight loss
- Low grade fever
- Arthralgia
- Respiratory symptoms
Insidious = chronic course + permanent damage, respiratory complaints w/o constitutional symptoms/symptoms referable to organs other than the lung
Lung sarcoidosis
90% of cases
Dry cough, SOB on exercise vs asymptomatic
Grading by CXR stages -
0 - normal
I - bilateral hilar lymphadenopathy w/o lung involvement
II - bilateral hilar lymphadenopathy w/ lung involvement
III - lung involvement w/o bilateral hilar lymphadenopathy (less likely to resolve)
Advanced cases - pulmonary HTN, fibrosis, destruction/obliteration lung vasculature, chronic hypoxaemia
Eye sarcoidosis
May be asymptomatic —> refer to Opthal for all patients for slit lamp and ophthalmoscope exam
Anterior/posterior uveitis Chorioretinitis Periphlebitis Papilloedema Retinal haemorrhage Keratoconjunctivitis sicca Lacrimal gland involvement
Late complications in untreated cases -
Secondary glaucoma
Cataract
Blindness
Reticuloendothelial sarcoidosis
Peripheral LN - cervical, supraclavicular, axillary, inguinal
Intrathoracic LN
Mesenteric LN
Retroperitoneal LN
Spleen - hypersplenism, pancytopenia
Bone marrow (rare)
Liver sarcoidosis
Mild hepatomegaly + mild cholestasis
Severe chronic cholestasis syndrome (rare)
Portal HTN (rare)
Budd-Chiari syndrome (rare)
Neurosarcodosis
Cranial nerve involvement —> facial paralysis (common)
Aseptic meningitis Seizures Pyramidal tract Optic nerve dysfunction Papilloedema Hypothalamic/pituitary lesions —> diabetes insipidus, hypopituitarism Cognitive impairment
MSK sarcoidosis
Transient vs chronic polyarthralgias (arthritis uncommon)
Asymptomatic muscle involvement (symptomatic diffuse/nodular myopathy rare)
Osteolytic bone lesions on hands and feet (uncommon)
Heart sarcoidosis
Arrhythmias (supraventricular, ventricular)
Complete heart block
Sudden death
Congestive heart failure
Cor pulmonale (secondary to chronic pulmonary fibrosis)
Ix - cardiac MRI/PET scan
Other organ sarcoidosis
Upper respiratory tract —> nasal stuffiness
Parotid - bilateral parotid enlargement, xerostomia
Transient/persistent hypercalcemia and hypercalciuria due to increased production of 1,25 dihydroxyvitamin D by granulomas —> nephrocalcinosis, nephrolithiasis
Renal - interstitial lymphocytic and granulomatous nephritis
Course/prognosis
Acute sarcoidosis resolves spontaneously without sequelae within 2-5 years
Lofgren syndrome -
excellent prognosis
Recurrence after spontaneous remission
Chronic progressive sarcoidosis sometimes assoc with irreversible fibrotic changes
Pregnancy not C/I except in severe chronic disease
Relapse post partum
Specific lesions (histopathologically display sarcoidosis granulomas)
Maculopapules Nodules and Plaques Lupus pernio Scar sarcoidosis Subcutaneous sarcoidosis
Red-brown/red-violaceous in colour
Multiple
Asymptomatic
Diascopy - subtle brown-yellow/apple jelly colour
Non-specific lesions
Erythema nodosum
Maculopapular sarcoidosis
Most common specific lesion
Transient, appear to herald onset of sarcoidosis
Yellow-brown/red-brown
No clinically evident epidermal change
Face - mainly periorbital, nasolabial folds
Other sites also including mucous membranes
Papular sarcoidosis of the knees - frequently with linear arrangement and Lichenoid appearance, polarisable foreign bodies in most biopsies, transient
Resolve spontaneously or < 2yrs with treatment without significant scarring (favourable prognosis)
Commonly assoc with acute systemic sarcoidosis - hilar LN, peripheral LN, erythema nodosum, acute uveitis, parotid enlargement
DDx - Xanthelasma Rosacea Secondary syphilis LE Trichoepithelioma Sebaceous adenoma Syringoma GA Lichen nitidus
Nodular and plaque sarcoidosis
Multiple round/oval infiltrated reddish-brown plaques
Thicker, more indurated, persistent than papules
Sometimes mamillated (rounded protuberances)
Tend to recur after treatment
Can leave permanent scarring when lesions resolve
Assoc with chronic systemic sarcoidosis - pulmonary fibrosis, peripheral LN, splenomegaly, chronic uveitis
Disease activity >2 yrs
DDx - Lupus vulgaris NLD GA Leprosy Morphoea DLE Leishmaniasis
Lupus pernio
Infiltrated red-violaceous plaques
Disfiguring
Nose, cheeks - prominent telengiectatic component Ears Lips Forehead Fingers
Painless
Doesn’t tend to ulcerate
Assoc with chronic course -
Sarcoidosis of upper respiratory tract (esp when there is involvement of nasal rim) - unique to lupus pernio
Bone cysts esp terminal phalanges - unique to lupus pernio
Pulmonary fibrosis
Chronic uveitis
DDx -
Rosacea
Lupus vulgaris
DLE
Scar sarcoidosis
Involve old scars from surgery, trauma, acne, gene puncture, vaccination, herpes zoster, Mantoux test
Old scars become infiltrated and red —> sarcoidal granulomas histopathologically
Frequently on knees
Tends to follow activity of the disease I.e. appear at onset
Assoc with - Chronic pulmonary and mediastinal involvement Peripheral LN Uveitis Bone cysts Parotid infiltration
Tattoo sarcoidosis is a variant - occurs decades after tattooing (DDx foreign body reaction to tattoo pigment)
Subcutaneous sarcoidosis
Sarcoidosis granulomas limited to subcut tissue
Multiple indurated subcut nodules in the extremities
Covered by normal-appearing skin
Mostly involves forearms with indurated linear bands from elbow to hand (fusiform)
Painless/non-tender
Appears at the onset of systemic sarcoidosis
Assoc with stage I sarcoidosis CXR change
Favourable prognosis - systemic sarcoidosis < 2 yrs
DDx - Epidermal cyst Lipoma Calcinosis Rheumatoid nodules Morphoea Cutaneous mets
Less common forms of cutaneous sarcoidosis
Angiolupoid sarcoidosis Hypopigmented sarcoidosis Lichenoid sarcoidosis Ulcerative sarcoidosis Psoriasiform sarcoidosis Verrucous sarcoidosis Ichthyosiform sarcoidosis Erythrodermic sarcoidosis Necrobiosis-lipoidica like lesions Morphoea-like lesions Livedo
Angiolupoid sarcoidosis
Some consider this to be discrete variant of lupus pernio with prominent large telengiectatic venules
Single raised plaque on bridge of the nose, entrap face, ears, scalp
Hypopigmented sarcoidosis
Hypopigmented
Well demarcated round to oval patches
Some lesions —> Erythematous papules in the centre of the hypopigmented patch —> fried egg appearance
Limbs
Interface dermatitis assoc with sarcoidal granulomas may explain hypomelanosis
Lichenoid sarcoidosis
More frequent in children
Small flat topped, dome shaped red/skin coloured papules
Wickham striae absent
Extensive on trunk, limbs, face
Ulcerative sarcoidosis
Usually develops on papulonodular/atrophic lesions on the lower legs
Heals with scarring
Psoriasiform sarcoidosis
May be clinically indistinguishable from psoriasis
Though psoriasis is salmon pink, have larger scale, heals without scarring
Verrucous sarcoidosis
Lower extremities
Assoc with African descent and long-standing systemic sarcoidosis
Ichthyosiform sarcoidosis
Adherent polygonal grey brown scales
Lower extremities
African descent
Compact orthokeratosis, diminished granular layer, sarcoidosis granulomas
Erythrodermic sarcoidosis
Infiltrated red plaques coalescing over large areas
Some areas of skin spared
Necrobiosis lipoidica like lesions
Pink-violaceous plaques with depressed centres
Shins
Morphoea-like lesions
Indurated atrophic plaques
Some show linear distribution resembling linear morphoea
Dermal sclerosis + sarcoidal epitheliod granulomas
Livedo
Japanese women
Epitheliod granulomas around blood vessels with luminal narrowing
Eye, CNS involvement
Special locations of specific cutaneous lesions of sarcoidosis
Scarring alopecia
Nail changes - assoc with bony cysts of terminal phalanx, chronic course
- Splinter haemorrhage
- Thinning
- Thickening
- Subungual hyperkeratosis
- Pitting
- Longitudinal ridging
- Trachyonychia
- Onycholysis
- Total loss of nail
- Pterygium
- Paronychia
Oral -
Diffuse submucous thickening
Firm nodule buccal mucosa
Genital
- testicular/epidydymal mass
- vulva
Non specific sarcoidosis lesions
Erythema nodosum (most common)
- Frequently initial manifestation of sarcoidosis
- Marker of acute, benign, self-limited sarcoidosis
- Lofgren syndrome (erythema nodosum, bilateral hilar and right paratracheal LN +/- pulmonary infiltrates) - may be accompanied by fever, polyarthralgia, uveitis - very good prognosis, resolves spontaneously within 1 yr
Erythema multiforme
Prurigo
Cutaneous calcinosis
Clubbing - poor prognostic sign
Pseudo-clubbing (granulomatous infiltrate of the terminal phalanx)
Sweet syndrome - assoc with onset of acute sarcoidosis
Investigations/basic assessment
History including occupational, environmental exposures
Physical exam
Ophthal exam - slit lamp, ophthalmoscopic exam
CXR
Standard haem, biochem profiles -
- FBC
- LFT
- UEC
- Urine and serum calcium level
- Serum ACE - 60% increased level
ECG
PFT including spirometry and diffusing capacity for carbon monoxide (DLCO) - decreased forced vital capacity, DLCO
Tuberculin skin test - negative
Biopsies for histo and culture for mycobacteria and fungus
If requiring oral steroids - baseline bone mineral density test
Consider High res CT if CXR has atypical findings (not indicated when CXR has typical sarcoidosis findings) - Bilat hilar LN, widespread pulmonary infiltrates
Consider F-FDG PET scan - detection of occult granuloma sites for biopsy, assess activity and extension of sarcoidosis, detect residual activity in those with fibrotic pulmonary sarcoidosis
Diagnostic criteria
Based on compatible clinical + radiological picture
Demonstration of non-caseating granulomas —> negative cultures for mycobacteria, fungus
When clinical + radiological findings not typical esp with stage 0 CXR —> advisable to obtain at least 2 positive biopsies (transbronchial, skin, peripheral LN)
Histo confirmation may not be necessary in Lofgren syndrome (recognisable)
Management for systemic sarcoidosis
Treatment of choice = Oral pred
30-40mg/d, with gradual reduction to 5-10mg/d or 10-20mg/48hr for at least 1 yr
1mg/kg/d may be required for severe uveitis, neurosarcoidosis, symptomatic cardiac involvement
Steroid sparing agent can be considered if oral pred cannot be withdrawn
- MTX for both skin + lung disease
Cutaneous lesions frequently recur when tapering oral pred used for systemic sarcoidosis
When no significant systemic sarcoidosis to justify oral pred, options for skin sarcoidosis not completely effective
Rx may be unnecessary for cosmetically insignificant/asymptomatic skin lesions
First line Rx for mild to moderate skin disease
Potent TCS
ILCS triamcinolone acetonide 5-20mg/mL every 3-4 weeks
First line Rx for severe skin disfigurement/lupus pernio
Oral pred 20-60mg/d until clinical response (typically 1-3 months), then tapered by 5-10mg/wk to the lowest dose that prevents relapse
If requiring at least 10mg/d oral pred, add steroid sparing agent
Osteoporosis -
- Oral calcium to prevent osteoporosis (increased risk in sarcoidosis, oral pred) if no hypercalcemia/nephrolithiasis
- Bisphosphonates to treat steroid-induced osteoporosis
- Use of vitamin D controversial due to increased production of vit D from granulomas that causes hypercalcaemia/hypercalciuria
Second line Rx for mild to moderate chronic/recalcitrant skin disease
1st Rx to be initiated = Tetracycline (Minocycline 100mg BD for 3 months)
- poor response in lupus pernio
If unsatisfactory to 3 months minocycline —> add Antimalarials (HCQ 200-400mg/d, chloroquine 250-500mg/d)
If no improvement with HCQ —> add MTX
(Response may take at least 6 months)
3rd line Rx for refractory skin sarcoidosis
Infliximab
Adalimumab
Other non-systemic Rx for skin sarcoidosis
Topical Rx-
- Topical tacrolimus
- Topical psoralen gel
Physical Rx -
- UVA1
- PDT
- CO2 laser
- PDL
- RTX
Surgery
Cutaneous/idiopathic sarcoid reaction
Skin sarcoid granulomas of unknown aetiology
Absence of other organ involvement
Important to follow up —> Some will develop involvement of other organs and fulfil criteria for sarcoidosis
