Sarcoidosis Flashcards
Immune cells which play a role
Increased production of Th1 cytokines, including interleukin (IL)-2 and interferon (IFN)-γ, as well as release of tumor necrosis factor (TNF)-α by macrophages, leads to B-cell stimulation and hypergammaglobulinemia. IL-12 is also thought to play a role in sarcoidosis as are CD4+ T cells of the Th17 subtype3a.
What % of ppl with sarcoidosis have skin lesions?
30%
Favoured sites
Sarcoidal lesions favor the face, lips, neck, upper trunk and extremities
Clinical features of lupus pernio
Lupus pernio is characterized by papulonodules and plaques, primarily involving areas most affected by cold (i.e. pernio), including the nose, ears and cheeks; there is often a beaded appearance along the nasal rim. More common in women. Seldom resolve.
Associations of lupus pernio
chronic sarcoidosis of the lungs (approximately 75% of patients), upper respiratory tract (approximately 50% of patients), cystic lesions within the bones and phalanges.
DDx of lupus pernio
Wegeners, malignant pleomrophic lymphoma, lymphoma cutis, BCC, SCC, leishmaniasis, cutaneous lupus.
Tx of lupus pernio
Establish Diagnosis. Evaluate for systemic sarcoidosis. High potency topical and IL steroids, HCQ, MTX, MMF, Infliximab (3-7mg/kg) at 0,2,6 weeks, thalidomide.
Lofgren syndrome
IF NELA Acute iritis Fever EN lymphadenopathy Migratory arthritis 95% HLADRB1*03 +ve will resolve in 2 years.
Heerfordt syndrome
PUFF
(uveoparotid fever) includes parotid gland enlargement, uveitis, fever, and cranial nerve palsies, usually of the facial nerve.
% with hypercalcaemia and why?
10%, increase in calcitriol synthesis by sarcoidal histiocytes
What occurs/does not occur in childhood sarcoidosis
Lung involvement rare
triad of arthritis, uveitis, cutaneous lesions + constitutional Sx.
Investigations & expected results
FBC - leukopenia, lymphopenia ESR - elevated eLFTs - check Ca, liver involvement, kidney involvement ACE: may be elevated in 60% VitD - may be high urinary calcium: may be high - risk of nephrolithiasis CXRay: bilateral hilar adenopathy gadolinium enhancement on MRI/PET, Spirometry DLco, KLco Ophthal: slit lamp ECG, Echo TB skin test - may be depressed sputum MCS exclude infection Kviem test - not done anymore Bx: see histo card
Histo
naked granulomas. Epithelioid cells with pale staining nuclei.
No caseation.
Inclusion bodies eg Schaumann (cytoplasmic inclusion body), Asteroid (stellate bodies): central core with radiating spicules.
Diagnosis
is a dx of exclusion, requires proof in 2 separate organs, but histological confirmation is not required in second organ
Types of sarcoidosis
localised vs generalised popular/micropapular plaque lupus pernio Subcutaneous Annular Angiolupoid Scar Verrucous Photodistributed Ichthyosiform Mucosal/nail/alopecia Atrophic Ulcerative Erythrodermic
Other name for subcutaneous sarcoidosis
Darier-Roussey
Causes of drug induced sarcoidosis
IFNalpha, TNFalpha
What to do if histo comes back with granuloma
Incisional biopsy for atypical mycobacteria, TB (eg lupus vulgaris) and deep fungal culture. Chest xray, QF gold
Histo DDx of sarcoidal granuloma
Deep fungal, mycobacterial
FB eg silica, tattoo, beryllium (should be polarised), granulomatous MF, crohns, granulomatous rosacea, Hodgkin
oral pred dose for systemic disease
1mg/kg for 4-6 weeks then slow taper over months-years
Treatment options for cutaneous sarcoidosis
Low dose pred Potent topical CS, topical calcineurin, IL steroids, PUVA HCQ minocycline 200mg/day MTX 10-25mg/week thalidomide 50-300mg/day isotretinoin 1mg/kg/day for 3-8 months allopurinol 100-300mg/day Infliximab -but may also trigger it (etanercept trial terminated early due to lymphoproliferative)
General prognosis
• 60% these will resolve with no problems in 2-5 years but is chronic or progressive in 10-30%
Organs affected
o May affect any organ (maybe not adrenal)
Most frequently affected: lymph nodes, lungs, liver, spleen, skin, eyes, small bones of hands, feet, salivary glands
What is the Kveim test?
o Kveim rection is positive in most active cases (spleen of +ve patient injected into suspected patient – if granuloma present in 4-6 weeks, +ve)
scar sarcoidosis
Scar - prefers traumatised tissue, around embedded FB. Inflammation of old scars may parallel or precede systemic disease activity. May be tender or pruritic.
1) acute eruptive phase, 2) later stage – may be warning sign of other organ involvement, 3) inoculation sites
Can be a warning sign of systemic disease
Most common on knees
Angiolupoid
Angiolupoid: pink papules and plaques with prominent telangiectasis on face and may be a variant of lupus pernio. Affects females, almost always at the side of the bridge of the nose, corner of the eye, below the inner edge of the eyebrow or adjacent cheek.
What is mikulicz syndrome
Mikulicz syndrome (bilateral enlargement of lacrimal, parotid, sublingual and submandibular glands)
Examination
Full skin exam - ?EN lymph nodes HSM lungs neuro red eyes
History
Onset of condition Systems review eg lungs, eyes, CNS, abdo pain, kidney pain, arthritis cough, sob exposures during occupation, TB exposure
Good prognostic
females
EN + fevers and arthralgias (Lofgren) – 80% spontaneous remission in 4-6 weeks
Stage I CXR vs II,III
+ve tuberculin test and normal globulin levels
HLA-B28 – more likely to spontaneously resolve
60% f ppl with stage 1 pulmonary disease will have recovered within 2 years
Papular type (small nodular)
Poor prognosis
African descent Extrathoracic disease Stage II-III Age >40 Splenic involvement Lupus pernio (URT involvement, pulmonary fibrosis and bony cyst associations) Disease duration >A 2 years FVC
Indications for tx
Symptomatic pulmonary disease Progressive or persistent parenchymal lung disease after 2 years Posterior ocular disease or anterior disease Fever or weight loss Liver disease with significant dysfunction or hepatosplenomegaly (synthetic dysfunction) Skin disease or lymphdenompathy Hypercalcaemia Nervous system disae Myocardial Myopathy or myositis Thrombocytopenia Other significant organ involvement
Monitoring
At each visit:
RV 6 monthly if treated
If no therapy rv 12 monthly
Follow for at least 3 years after therapy discontinued
Med Hx: SOB, fatigue, cough, weight loss, ocular problems, neuro problems
Exam: lung, cardiac, abdo, skin, lymph nodes, neuro exam
Annual tests: Eye, ECG, Chest xray, RFTs, FBC, serum chemistries
Associated diseases
- Infections – particularly wart virus
- Immunologically mediated conditions eg thyroid disease, connective tissue
- Effects of infiltration: granulomas in pituitary or thyroid
- Vasculitis with sarcoidosis
- Malignancy: may precede development of lymphoma by 18 months to 28 years. Increased risk of thyroid cancer and leukaemia
- NLD and GA
Other sarcoidal like reactions
FB, crohns, infections, lymphoma, granulomatous cheiltiis
Exposures that are triggers
Hep c, interferon alpha, mycobacterium, p acnes, ebv, hsv
Dust, metals, mould, combustible wood products
Eyes involved how often
25-75%
Eye signs
Uveitis, cataracts, glaucoma, iris nodules, retinochoroiditis, conjunctivitis, lacrimal gland involvement, optic nerves, orbital involvement, heerfordt syndrome (anterior uveitis)
Enlarged lymph nodes
50%
Spleen enlarged in %
15%
% Cardiac involvement
5%
Mikulicz syndrome
Bilateral enlargement of lacrimal, parotid, sublingual, submandibular glands
Raised lfts in what %
1/3
Ecg abnormal in %
14%
Cns involvement
Cranial nerve palsies, diabetes insipidus, hypopituitarism, endocrine abnormalities
Associations with sarcoidosis
Vain me Vasculitis, AI eg thyroid, chronic urticaria, ctd Infection: hpv, aspergillus, mycetoma Nld and ga MalignancY: solid tumours, lymphoid Endocrine: infiltration eg cushings, DI
% hypercalciuria
40%, 11% hypercalcaemia
Bone and joints
Polyarthralgia, bone cysts, small hands and feet classically
Cardiac
20-50% often young, sudden death, myocarditis, conduction, pericarditis
% stage 1 on chest X-ray
35-45%
If abn chest X-ray - % with abnormal lung function tests
50-70%
3 ocular syndromes
Lofgrens
Heerfordt
Mikulicz
Kc sicca and parotid, lacrimal enlargement
Lupus pernio, chronic iridocyclitis, bone cysts, pulmonary fibrosis
% ocular involvement
25-75%
Ddx
Ga, nld Tb, leprosy, lupoid leishmaniasis Rosacea Cutaneous crohns Syphilis
