Sarcoidosis

Question 1

Immune cells which play a role

Answer 1

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.

Question 2

What % of ppl with sarcoidosis have skin lesions?

Answer 2

30%

Question 3

Favoured sites

Answer 3

Sarcoidal lesions favor the face, lips, neck, upper trunk and extremities

Question 4

Clinical features of lupus pernio

Answer 4

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.

Question 5

Associations of lupus pernio

Answer 5

chronic sarcoidosis of the lungs (approximately 75% of patients), upper respiratory tract (approximately 50% of patients), cystic lesions within the bones and phalanges.

Question 6

DDx of lupus pernio

Answer 6

Wegeners, malignant pleomrophic lymphoma, lymphoma cutis, BCC, SCC, leishmaniasis, cutaneous lupus.

Question 7

Tx of lupus pernio

Answer 7

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.

Question 8

Lofgren syndrome

Answer 8

IF NELA
Acute iritis
Fever
EN
lymphadenopathy
Migratory arthritis 
95% HLADRB1*03 +ve will resolve in 2 years.

Question 9

Heerfordt syndrome

Answer 9

PUFF
(uveoparotid fever) includes parotid gland enlargement, uveitis, fever, and cranial nerve palsies, usually of the facial nerve.

Question 10

% with hypercalcaemia and why?

Answer 10

10%, increase in calcitriol synthesis by sarcoidal histiocytes

Question 11

What occurs/does not occur in childhood sarcoidosis

Answer 11

Lung involvement rare

triad of arthritis, uveitis, cutaneous lesions + constitutional Sx.

Question 12

Investigations & expected results

Answer 12

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

Question 13

Histo

Answer 13

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.

Question 14

Diagnosis

Answer 14

is a dx of exclusion, requires proof in 2 separate organs, but histological confirmation is not required in second organ

Question 15

Types of sarcoidosis

Answer 15

localised vs generalised
popular/micropapular
plaque
lupus pernio
Subcutaneous
Annular
Angiolupoid
Scar
Verrucous
Photodistributed
Ichthyosiform 
Mucosal/nail/alopecia 
Atrophic
Ulcerative 
Erythrodermic

Question 16

Other name for subcutaneous sarcoidosis

Answer 16

Darier-Roussey

Question 17

Causes of drug induced sarcoidosis

Answer 17

IFNalpha, TNFalpha

Question 18

What to do if histo comes back with granuloma

Answer 18

Incisional biopsy for atypical mycobacteria, TB (eg lupus vulgaris) and deep fungal culture. Chest xray, QF gold

Question 19

Histo DDx of sarcoidal granuloma

Answer 19

Deep fungal, mycobacterial

FB eg silica, tattoo, beryllium (should be polarised), granulomatous MF, crohns, granulomatous rosacea, Hodgkin

Question 20

oral pred dose for systemic disease

Answer 20

1mg/kg for 4-6 weeks then slow taper over months-years

Question 21

Treatment options for cutaneous sarcoidosis

Answer 21

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)

Question 22

General prognosis

Answer 22

• 60% these will resolve with no problems in 2-5 years but is chronic or progressive in 10-30%

Question 23

Organs affected

Answer 23

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

Question 24

What is the Kveim test?

Answer 24

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)

Question 25

scar sarcoidosis

Answer 25

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

Question 26

Angiolupoid

Answer 26

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.

Question 27

What is mikulicz syndrome

Answer 27

Mikulicz syndrome (bilateral enlargement of lacrimal, parotid, sublingual and submandibular glands)

Question 28

Examination

Answer 28

``` Full skin exam - ?EN lymph nodes HSM lungs neuro red eyes ```

Question 29

History

Answer 29

``` Onset of condition Systems review eg lungs, eyes, CNS, abdo pain, kidney pain, arthritis cough, sob exposures during occupation, TB exposure ```

Question 30

Good prognostic

Answer 30

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)

Question 31

Poor prognosis

Answer 31

``` 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 ```

Question 32

Indications for tx

Answer 32

``` 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 ```

Question 33

Monitoring At each visit:

Answer 33

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

Question 34

Associated diseases

Answer 34

- 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

Question 35

Other sarcoidal like reactions

Answer 35

FB, crohns, infections, lymphoma, granulomatous cheiltiis

Question 36

Exposures that are triggers

Answer 36

Hep c, interferon alpha, mycobacterium, p acnes, ebv, hsv | Dust, metals, mould, combustible wood products

Question 37

Eyes involved how often

Answer 37

25-75%

Question 38

Eye signs

Answer 38

Uveitis, cataracts, glaucoma, iris nodules, retinochoroiditis, conjunctivitis, lacrimal gland involvement, optic nerves, orbital involvement, heerfordt syndrome (anterior uveitis)

Question 39

Enlarged lymph nodes

Answer 39

50%

Question 40

Spleen enlarged in %

Answer 40

15%

Question 41

% Cardiac involvement

Answer 41

5%

Question 42

Mikulicz syndrome

Answer 42

Bilateral enlargement of lacrimal, parotid, sublingual, submandibular glands

Question 43

Raised lfts in what %

Answer 43

1/3

Question 44

Ecg abnormal in %

Answer 44

14%

Question 45

Cns involvement

Answer 45

Cranial nerve palsies, diabetes insipidus, hypopituitarism, endocrine abnormalities

Question 46

Associations with sarcoidosis

Answer 46

``` 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 ```

Question 47

% hypercalciuria

Answer 47

40%, 11% hypercalcaemia

Question 48

Bone and joints

Answer 48

Polyarthralgia, bone cysts, small hands and feet classically

Question 49

Cardiac

Answer 49

20-50% often young, sudden death, myocarditis, conduction, pericarditis

Question 50

% stage 1 on chest X-ray

Answer 50

35-45%

Question 51

If abn chest X-ray - % with abnormal lung function tests

Answer 51

50-70%

Question 52

3 ocular syndromes

Answer 52

Lofgrens Heerfordt Mikulicz Kc sicca and parotid, lacrimal enlargement Lupus pernio, chronic iridocyclitis, bone cysts, pulmonary fibrosis

Question 53

% ocular involvement

Answer 53

25-75%

Question 54

Ddx

Answer 54

``` Ga, nld Tb, leprosy, lupoid leishmaniasis Rosacea Cutaneous crohns Syphilis ```