Sarcoidosis & Granulomatous Flashcards
What is Lofgren’s syndrome?
Acute self-limiting form of sarcoidosis Loaf around all day and you FAILE: Fever Arthralgia + Migratory polyarthritis Iritis Lymphadenopathy - bilateral hilar on CXR Erythema nodosum NSAIDs 90% resolve in 2 years dont confuse with Loefflers syndrome
What is Mikulicz’s syndrome?
Milk - think of glands Bilateral swelling of parotid, salivary and lacrimal glands Associations; Sjogrens SLE Leukaemia Hodgkins Syphylis Sarcoidosis Tuberculoisis
What is Heerfordt’s syndrome?
Rare manifestation of sarcoidosis; Hear me PUFF Parotid swelling Uveitis Fevers Facial nerve palsies - sometimes
T/F
subcut GA needs aggressive Rx
F
dont treat it
resolves spontaneously
Treatment ladder for GA?
Do nothing 50% resolve in 2 years - esp if localised dont treat kids - resolve dont treat subcut gA - resolves Potent TCS and/or TCNI ILCS second line for localised LN2 cryo - 3rd line for localised Many 4th line options; PDT UVA1 Immiquimod PDL laser IFN injection scarification or excision
If generalised or severe; UVA1 first line Isotretinoin Dapsone topical tacrolimus PDT PUVA good for generalized GA – oral or topical psoralens NbUVb less good for generalized GA Many other 3rd line options inc; Hydroxychloroquine Nicotininamide CsA TNF blockers
Investigations in GA?
Fasting glucose and urine dip for sugar
TFTs and thyroid autoantibodies
FBC, HIV test and Hep C if generalised
Consider RF or antiCCP if rheum nodule differential
T/F
NLD seen in 3% of diabetics
F
0.3%
NLD treatment ladder?
Avoid trauma as can cause ulceration
Stop smoking
If diabetic optimize control
Urgent biopsy if clinical suspicion of SCC
Potent TCS under occlusion changed weekly esp for early lesions - 1st line
ILCS - after TCS
Then TOP NLD - 2nd line Rxs;
T - Tacrolimus ointment
OP - Oral Prednisolone short course (5 weeks) may halt progression
N - High dose Nicotinamide (500mg TDS) (some evidence) – starts as 500mg OD for 1wk, then BD for 1 wk then TDS – 2nd line
L - Light = topical PUVA
Dye - Clofazimine 200mg OD – 2nd line
T/F
Aspirin or assasantin/dipyridamole work for some people with NLD
F
shown to be ineffective
What are later options for NLD Rx?
Topical;
- Tretinoin
- G-CSF
- bovine collagen
- Perilesional heparin injection
Systemic;
- Chloroquine, hydroxychloroquine (some evidence)
- CsA (some evidence)
- Etanercept (some evidence)
- Infliximab (some evidence)
- Pentoxyfiline, stanozolol, inositol niacinate, nicofuranose, ticlopidine hydrochloride
- Thalidomide
- Fibrinolytic agents (streptokinase, tPA)
- Tretinoin
- Prostaglandin
- MMF, CsA
- IVIg
Physical and surgical;
- UVA1
- PDT
- Hyperbaric oxygen
- Split thickness autografting and immunomodulatory therapy
- Pulsed dye laser – improved erythema and telys but skin breakdown risk
- Simple excision and grafting (SSG) if ulcerated
- Grafting with bioengineered dermal tissue
T/F
optimizing diabetic control improves NLD
F
No link between diabetic control and developing or curing NLD
But diabetics with NLD have inc risk of retinopathy and nephropathy so should optimize to reduce these
Histo of actinic granuloma?
In mid and upper dermis there is an infiltrate of lymphocytes, histiocytes and foreign body type multi-nucleated giant cells
Dermal elastosis and Elastophagocytosis – elastin fibres in and around giant cells stain w/ EVG
Asteroid bodies in the granulomas
often solar elastosis
• No telys (cf NLD)
• No altered collagen (necrobiosis) or mucin
T/F
LN2 cryo works well for actinic granuloma
F
cryo not effective
No good treatment exists
Treatment ladder for actinic granuloma
sun protect and TIPP TCS ILCS PUVA Plaquenil/antimalarials
what conditions get rheumatoid nodules?
7-20% of patients with RA 75% with Feltys syndrome 5% patients with SLE rare assocs; ankylosing spondylitis granuloma annulare chronic active hepatitis infrequently in healthy children and adults
Histo of rheumatoid nodules?
Palisading granuloma around degenerated connective tissue (necrobiosis) and fibrin (fibrinoid necrosis, not mucin) in the deep dermis or subcutaneous tissue
Fibroblasts, histiocytes, and lymphocytes mainly; only a few multinucleated giant cells
Stain fibrin with MSB stain (Martius Scarlet Blue) stains fibrin red and collagen blue
Treatment ladder for granulomatous cheilitis/ orofacial granulomatosis?
Cold compresses and oral antihistamines for reducing erythema
Lip balm to protect against fissuring of the lips
TCS – triamcinolone or potent TCS
ILCS 10-40mg/ml (nerve blocks 1st); may need repeated due to tendency to relapse
Pred course +/- doxy to prevent flare when weaned
Doxy alone
Roxithromycin 300mg/day
Metronidazole +/- ILCS
Hydroxychloroquine
Clofazamine 100mg/day
TNFalpha – infliximab>adalimumab
Thalidomide
granulomatous cheilitis diagnosis requires biopsy
F
Granulomatous cheilitis is primarily a clinical diagnosis
Dilated lymphatic channels, non-specific inflammatory infiltrates, and oedema. In the later stages, the classic non-caseating granulomas are found
Absence of granulomata on biopsy does NOT exclude the diagnosis of granulomatous cheilitis
Investigations for granulomatous cheilitis?
Crohns and sarcoid are major concerns;
Biopsy for histopathologic examination: polarization and stains/cultures for fungi and acid-fast bacilli
FBC, ELFT including serum calcium
Angiotensin-converting enzyme level
CXR
C1-esterase inhibitor, C1-esterase inhibitor functional assays, C1, C2, and C4 levels
Dentist referral, if odontogenic infection suspected – must exclude this
Gastro referral if there are any gastrointestinal complaints – must always think of Crohns
Patch testing and food allergy testing
T/F
Pyostomatitis vegetans has granulomas on histo
F
histo shows eos not granulomas
Is a cobblestone-like mucosal thickening with warty vegetations
often accompanied by pyodermatitis vegetans with pustular eruption of intertriginous skin w/out granulomas
T/F
The following are reported triggers of sarcoidosis;
Environmental (mildew, mould, insecticides, combustible wood, firefighting, building materials, industrial organic dusts)
Infectious (mycobacteria, P. acnes, viruses (herpes, coxsackie B, CMV, EBV), Borrelia, Mycoplasma, chlamydia)
Drugs – Reports of sarcoid days to years after IFNα Rx or anti-TNFα Rx
T
T/F
sarcoid pts have reduced humoral immunity
F
depressed cell-mediated immunity
T/F
2/3 of sarcoidosis pts have skin involvement
F
1/3
often present to derm as skin noticed first
what are the DDs for cutaneous and lung sarcoid?
Skin; localised sarcoidal skin reaction Other granulomatous disease; TB, atypical myco Leprosy Syphilis brucellosis fungal Foreign-body reaction e.g. dermal fillers, Sea-urchin spines Lung DDs include above +; silicosis, berryliosis, zirconiosis Thesaurosis – pulmonary infiltration from polyvinyl-pyrrolidine hair sprays extrinsic allergic alvolitis (hypersensitivity pneumonitis - birds) mycoplasma
what are the classical and atypical types of cutaneous sarcoidosis?
Major skin types; Papular (very common) Plaque (very common) Nodular Maculopapular Annular (uncommon) Other classical mucocutaneous types; Lupus pernio (common) Scar sarcoid (common): Koebner phenomenon Subcutaneous (Darier-Roussy) (common) Angiolupoid form Mucosal involvement Nail involvement (affects one 1:400) Atypical forms Alopecia of scalp Atrophic forms Erythrodermic sarcoidosis (extremely rare) Hypopigmentation (esp afro-caribbeans) Ichthyosiform sarcoidosis Lichenoid sarcoidosis PMLE type Unilateral oedema of lower leg Miscellaneous Other; Lofgren’s syndrome: Heerfordt’s syndrome Mikulicz’s syndrome Reactive; EN Sweets
What are the associations of sarcoidosis?
Infections – prone to stubborn wart virus infections
Immunologically mediated conditions – autoimmune thyroid disease, CTD, lupus, chronic urticaria
Effects of infiltration – pituitary or thyroid gland causing endocrine disease
Vasculitis
Malignancy – increased risk of lymphoproliferative disease esp lymphoma
also leukaemia, cervix, lung, testis, uterus, thyroid, myloma
NLD and GA
What are the systemic features of sarcoidosis
Most important are; Lungs, skin, eyes, heart, CNS and calcium
General symptoms: Weight loss, fever, fatigue
Lungs: Asymptomatic or dyspnoea, cough, wheeze, chest pain, tightness (4 stages on CXR)
Eyes: anterior and posterior uveitis (anterior uveitis in 70%=most common eye feature), optic neuritis (medical emergency), dry eyes, diplopia, eyelid granulomas
- Classically ‘Millet-seed’ nodules on conjunctivae
Heart: often asymptomatic, sudden death, arrhythmias, heart failure, pericardial effusions, syncope
CNS: cranial nerve neuropathy is most common feature (frequently facial CN7 lower MN lesion i.e. Bell’s palsy), seizures
Calcium derangemnt is due to excess active vit D production; hypercalcaemia, hypercalciuria and nephrolithiasis
MSS: polymyositis and myopathy occur rarely
Other organs: liver, spleen, kidneys (nephrolithiasis), upper respiratory tract
Lymphadenopathy and haem derangements can occur
Joints: acute sarcoid arthritis often associated with EN (ankles and knees)
What is the effect of pregnancy on sarcoidosis?
may improve during pregnancy and relapse after
T/F
Most sarcoidosis cases resolve in 2-5 years
T
>60% of patients with sarcoidosis, granulomatous changes resolve without residua within 2-5 yrs
10-30% cases are chronic or progress to fibrosis
Which skin lesions of sarcoid are associated with better or worse prognosis disease?
Acute (favourable): EN, papular, scar,
Chronic and systemic disease: plaque, lupus pernio, ulcerative
T/F
erythem nodosum in sarcoid pts gives a poor prognosis
F
usually associated with ‘benign’ transient disease that does not require treatment with clear (stage 0) CXR and >80% complete resolution within 2 yrs
Outline the work up for a susepcted sarcoidosis case
Biopsy - usually done before proceeding to further work up
FBC – thrombocytopenia, lymphopenia, pancytopenia
ELFTs – elevated LFTs/bili (hepatic sarcoidosis)
serum and 24hr urinary calcium
serum ACE
Qgold (TB in DD or as trigger)
PA CXR
RFTs w/DLCO
ECG +/- Holter +/- Echo
Refer to respiratory - all confirmed/likely cases
Referral to ophthalmologist - all confirmed/likely cases
Refer to cardiologist - all confirmed/likely cases
Refer to neurologist - all confirmed/likely cases
Also;
Consider screening for infectious triggers; HSV, chlamydia, EBV, CMV, Mycoplasma, Mycobacteria
Consider screening for associations; AI screen, Vasculitis screen, Malignancy screen, TFTs, prolactin, visual fields
What are the CXR signs of sarcoidosis?
4 active stages;
0) 5-10% have normal CXR
1) bilateral hilar or mediastinal lymphadenopathy
2) 1+ fine ‘fluffy’ or coarse parenchymal lung infiltrates
3) parenchymal lung infiltrates w/out hilar adenopathy
4) lung fibrosis and pulmonary insufficiency – other features variable
Histo findings of sarcoidosis?
Epidermis normal
Non-caseating well-demarcated, ‘naked’ granulomas in dermis or subcutis
Inclusion bodies in giant cells of sarcoid include; Asteroid bodies (also in foreign body granulomas) and Schaumann (conchoids) bodies (dystrophic calcification)
No mucin
Always examine under polarised light for birefringent material that may mimic sarcoidosis. But FBs may be found and does not exclude sarcoid
Skin sarcoidosis Rx ladder?
Potent TCS under occlusion
ILCS; 5-10mg/ml
Oral corticosteroids for rapidly progressive or topically unresponsive followed by steroid-sparing agent;
1 mg/kg daily (maximum 60 mg) for up to 3 months, and then tapered if improvement or a stable level is reached, to a maintenance dose of 5–10 mg on alternate days for several months
Hydroxychloroquine
Methotrexate
AZA then MMF used 2nd or 3rd line in Australia after MTX
Others;
- Minocycline/Doxycycline
- Thalidomide
- Isotretinoin
- Anti-TNF alpha (infliximab, adalimumab)
- CO2 laser for lupus pernio
- UVA1 for forehead plaque sarcoid or PUVA
- PDT
- Excision of stubborn small areas
Follow up regime in sarcoidosis?
Rw at least every 6/12 if active disease
If stable disease off treatment rw annually
If resolved and off Rx rw annually for 3 years in case of relapse
Evaluation at every visit
• Medical history: skin lesions, wt loss, fever, fatigue, dyspnea, shortness of breath, cough, ocular problems, upper airway complaints, symptoms of nephrolithiasis, palpitations, syncope, symptoms of CCF, and neurologic complaints
• Examination: lung, cardiac, abdomen and skin, palpate of LNs and neurologic examination
Tests ordered annually
• Ophthalmologic examination: slit-lamp and fundoscopic eye examination
• Electrocardiogram (controversial)
• Chest radiograph
• Pulmonary function tests
• FBC, ELFT, calcium
