Teaching Clinic: Slide Session Flashcards
Cutaneous lupus erythematosus
***Acute cutaneous LE (ACLE)
1. Localised malar rash
2. Generalised mobiliform rash
3. Toxic EM-like (Rowell’s syndrome)
***Subacute cutaneous LE (SCLE)
1. Annular SCLE
2. Papulosquamous SCLE
3. Toxic EM-like (Rowell’s syndrome)
Chronic cutaneous lupus erythematosus (CCLE)
1. **Discoid LE (DLE)
- Localised
- Generalised
- Hypertrophic / Verrucous DLE
- Mucosal DLE
2. **Tumid LE (LET)
3. ***Lupus panniculitis / Lupus profundus (LEP)
4. Chilblain LE
5. Lichenoid DLE (LE-lichen planus overlap)
Primary locations of the infiltrates:
- ACLE, SCLE: Superficial dermis
- DLE: Superficial + Deep dermis + Peri-adnexal
- LET: Superficial + Deep dermis
- LEP: SC fat
AutoAb in Cutaneous LE
ACLE: ANA (95%), Anti-dsDNA, Anti-Sm
SCLE: ANA (75-80%), Anti-Ro (50-70%), Anti-La (30-40%)
DLE: ANA (25%)
LET: Usually negative ANA
LEP: ANA (50-60% but usually in patients with features of SLE)
Association with SLE:
- ACLE: +++
- SCLE: ++
- DLE: + to ++
- Other variants:
—> Bullous eruption of SLE: ++++
—> Rowell’s syndrome: ++ to ++++
Subacute cutaneous LE (SCLE)
- ~10% of patients with LE
- 50% of patients will have >=4 features that classify them for a diagnosis of SLE
- Age of onset: 3rd / 4th decade
- F:M = 3-4:1
Clinical features:
- **Highly photosensitive
—> Affected areas: face, V of neck, upper chest and upper back, shoulders, extensors of arms and forearms
- **Non-scarring
- Scaly **psoriasiform **annular erythematous plaques and papules
- Borders may show crusting, vesiculation
- Follicular plugging and hyperkeratosis are not prominent
DDx:
- Psoriasis
- Tinea corporis
- EAC (Erythema Annulare Centrifugum)
- Lichen planus
Immunology:
- ANA +ve (70-80%)
- Anti-Ro, Anti-La (high prevalence of positivity)
—> Anti-Ro (+ve in 50-70%, especially the annular variant)
—> Anti-La (+ve in 30-40%)
- Since Anti-Ro autoantibodies are associated with Sjögren’s syndrome as well as SCLE, some patients have features of ***both conditions
Drug-induced SCLE
Multiple drugs
1. Cardiovascular medications
- ACE inhibitors (enalapril, lisinopril, captopril, ramipril)
- **CCB (diltiazem, verapamil, nifedipine)
- Beta-blockers (acebutolol, oxprenolol)
- Diuretics (*hydrochlorothiazide, spironolactone)
- Anti-fungals
- **Terbinafine, **Griseofulvin - PPI
- Omeprazole, Pantoprazole, Lansoprazole - Lipid lowering agents
- Simvastatin - NSAIDs
- ***Piroxicam
Management:
- Discontinuation of the causative drug will usually result in resolution of lesions
Discoid LE (DLE)
Epidemiology:
- F:M = 2:1
- Peak of onset: 4th decade in F, slightly later in males
Genetic factors:
- Positive associations with HLA-B7, B8, DR2, DR3, DQw1
- Familial cases do occur, although rare
External factors:
1. UV light and disease exacerbation
- Photo-aggravated disease can be present
- Both wavelengths shorter than 329nm and the whole range through UVB, UVA and visible light can produce lesions under experimental conditions
4. Reovirus
- Antibodies to reovirus RNA were found in 42% of patients
Clinical features:
1. Raynaud’s phenomenon (14%)
2. Chilblains (22%)
3. Non-specific arthralgia (25%)
4. Cutaneous signs
- Disseminated DLE: lesions **above + **below the neck
- Localised DLE: lesions ***limited to the head + neck
—> Face is most commonly affected
—> Other areas: scalp, ears (external canal and conchal bowl), V of neck, extensors of arms
—> Spares nasolabial folds
—> Lesions may be bilaterally although not necessarily symmetrical
—> Well demarcated scaly erythematous papules or plaques with an adherent scale extending into follicular orifices (Carpet tack sign: peeling the thick scale of a discoid plaque reveals horny plug protruding from a dilated pilosebaceous canal)
—> Wide follicular pits occur mainly in the concha or triangular fossa of the ear
—> Progression of follicular involvement results in scarring alopecia (30% of patients)
—> Presence of Koebner phenomenon
—> Depressed, atophic centre with depigmentation and telangiectasia
—> Peripheral hyperpigmentation or slight raised, red border (If relapse occurs, it usually starts within the reddish zone)
—> Calcification may occur
Immunohistochemistry:
- DIF +ve (Direct immunofluorescence) in 60% of DLE
- In DLE, positive lupus band test in non-lesional skin may be predictive of possible conversion to systemic disease
- In scarring alopecia caused by DLE, the deposits are around the hair follicles
Immunology:
- ANA +ve (25%)
Chilblain LE
- 6% of patients with DLE, predominantly female and smokers
- Chilblain-like lesions on the toes and fingers, but can also occur on the heels, calves, knees, knuckles, elbows, ears and nose
—> Violaceous, infiltrated, pruritic or painful papules and plaques which develop in response to cold
—> Ulceration is common in digital pulp lesions
—> Plaques may evolve over time to be atrophic with scarring and telangiectasia, indistinguishable from chronic DLE - Can be precipitated by pregnancy
- Usually occurs years after discoid lesions
Investigations:
- Cryofibrinogenaemia / Cold agglutins in some patients
- Anti-Ro +ve usually
Tumid LE (LET) (Tumid 腫脹的)
- Dermal LE
Clinical features:
1. Fixed smooth, indurated, erythematous to violaceous, single or multiple plaques or nodules
2. No epidermal changes (no scaling, follicular plugging)
3. Non-scarring
4. Photodistributed
Immunology:
- ANA +ve (40-50%, usually in low titres) (small case series)
Lupus panniculitis / Lupus profundus (LEP)
- Middle-aged women
- Uncommon form of Chronic cutaneous LE
- Occur alone / in the setting of SLE (10%)
- 50% of patients have overlying skin surface changes of classic DLE
- Clinical lesions can occur in 3-5% of patients with DLE although histological disease may be present in up to 30%
- Chronic remitting course
- Often occurs prior to other manifestations of LE
- If associated with SLE often portends a good prognosis
Clinical features:
1. Painful dermal / SC nodules on face, proximal extremities and trunk, Spares lower limbs
2. Firm, indurated, sharply defined, persistent
3. No epidermal skin changes
4. Healing results in lipoatrophy with depressed areas or anetoderma (depression or lesion caused by a loss of elastic tissue in the dermis)
5. Calcification and ulceration may occur
***Treatment of Cutaneous LE
General:
1. Sun protection
2. Sun avoidance
3. Sunscreen (broad spectrum sunscreens with UVA and UVB protection)
4. Smoking cessation
- Smoking is associated with poorer response to treatment with HCQ, immunomodulators
Specific:
1. Topical therapy
- Corticosteroids (useful in all forms of CLE)
- Calcineurin inhibitors (steroid sparing effect, may be used in DLE, SCLE, ALE)
- Retinoids (can be used in refractory DLE)
- Intralesional corticosteroids
- may be used in localised lesions of DLE, LET, LEP - Systemic
- Indications: widespread skin lesions, disfiguring, scarring, refractory to topical therapy
Antimalarials (1st line)
- Drug of choice for all subtypes of CLE
- Hydroxychloroquine, Chloroquine, Quinacrine (not available)
- Onset of action: 4-8 weeks
- Dosing:
—> HCQ: Adult <=6.5 mg/kg ideal BW per day
—> Chloroquine: Adult <=4 mg/kg ideal BW per day
—> The prior recommendation emphasised dosing by weight
—> However, most patients are routinely given ***400 mg of HCQ daily. This dose is now considered acceptable, except for individuals of short stature, for whom the dose should be determined on the basis of ideal body weight to avoid overdosage
- Pregnancy category C
2nd line:
1. Corticosteroids
- Indications in CLE: highly acute or severe lesions
- Avoid long term therapy in view of adverse effects
2. Methotrexate (MTX)
- Indications: Treatment refractory SCLE / localised DLE
3rd line:
1. Retinoids
2. Azathioprine
3. Mycophenolate Mofetil (MMF)
4. Thalidomide
5. IVIG
***SE of Antimalarials
- GI: nausea, diarrhoea (improves with time and with food)
- Dyspigmentation
- Blue gray to dark purple pigmentation can begin after approximately 4 months of receiving the medications
- Begins as isolated oval macules and progressively merge into larger lesions
- Hard palate is the most common site of antimalarial-induced pigmentation
- Other mucosal sites and the nails can be involved
- Quinacrine: distinctive lemon-yellow discoloration, which may involve all the skin, thereby mimicking jaundice
- Hypopigmentation, can also occur especially in patients on Chloroquine - Ocular changes
- **Irreversible retinopathy
- The risk of toxicity increases sharply toward 1% after 5 to 7 years of use, or a cumulative dose of 1000 g of HCQ. The risk increases further with continued use of the drug
- A **baseline examination is advised for patients to serve as a reference point and to rule out maculopathy, which might be a contraindication to their use
- Annual screening should begin ***after 5 years (or sooner if there are unusual risk factors)
***Panniculitis
- Inflammation of adipose tissue
- Presents clinically as **tender, **inflamed, ***SC nodules / plaques
- ***Ulceration with drainage may develop
Types:
Common:
1. **Erythema nodosum
2. **Lipodermatosclerosis
3. **Erythema induratum
4. **Lupus erythematosus panniculitis (LEP)
5. Childhood panniculitis
Less common:
6. **Pancreatic panniculitis
7. **Panniculitis-like T-cell lymphoma
8. Subacute nodular migratory panniculitis
9. α1-antitrypsin deficiency panniculitis
10. Cytophagic histiocytic panniculitis
***Approach to Panniculitis
History:
1. Duration of rashes
2. Presence of ulceration / drainage
3. Drug history
4. Preceding / Concurrent infective symptoms
5. Systemic review: fever, arthralgia, bowel symptoms, LOA / LOW
P/E:
1. Extent + Distribution of lesions
2. Concomitant venous insufficiency, alopecia / malar rash, respiratory + abdominal examination
Investigations:
1. Skin biopsy
- Confirm diagnosis + type of panniculitis
- Predominantly **septal, **lobular, **mixed septo-lobular panniculitis on histology
- Presence of **vasculitis can be seen in EI
- Systemic workup
- Depends on suspected type of panniculitis
—> Erythema nodosum: CBC, ESR, CXR, TB-spot, ASOT
—> Lipodermatosclerosis: Venous studies
Treatment:
1. Analgesia
2. Bed rest + Leg elevation
3. Stop causative drug (e.g. in case of EN)
4. Treat underlying systemic disease / infections
- Erythema nodosum
- F>M
- Acute eruption of inflamed, tender SC nodules, favouring the ***pretibial area bilaterally
- ***NO ulceration / drainage
- +/- Fevers, arthralgia, malaise
- Screen for ***systemic disease
Causes:
Most common:
1. **Idiopathic
2. **Streptococcal infections (esp. URTI)
3. Other infectious associations: **TB, Yersinia, Salmonella, Campylobacter
4. **Sarcoidosis
5. **IBD
6. **Drugs: OCP, sulphonamides, penicillins
Uncommon:
7. Neutrophilic dermatosis (e.g Sweet’s syndrome, Behcet’s syndrome)
8. **Pregnancy
10. **Malignancy (e.g. AML)
Lipodermatosclerosis
- Typically middle-aged to older with chronic venous disorders
- Favours lower extremities
- Strong association with obesity, venous insufficiency, systemic hypertension
Acute phase:
- Painful, warm, red-purple, poorly defined plaques with variable induration
- May be misdiagnosed as cellulitis
Chronic phase:
- Induration and hyperpigmentation of the lower legs, with “inverted champagne bottle” appearance
Erythema induratum (aka Nodular vasculitis)
- aka ***Nodular vasculitis
- F»M
- Tender, inflamed nodules to plaques on lower legs, esp. the calves
- ***Ulceration and drainage can occur
- Persistent, heal with scarring, tend to be recurrent
Causes:
Most common (記呢兩個ok):
1. **TB
2. **Idiopathic
(Uncommon:
3. Infectious associations (e.g. nocardia, pseudomonas, viral hepatitis)
4. Superficial thrombophlebitis
5. Hypothyroidism
6. RA
7. Crohn’s disease
8. Drugs (e.g. PTU))
