Autoimmune Disease of the Skin Flashcards
What is dermatitis herpetiformis? What condition is it associated with and how does it correlate with disease activity?
Autoimmune blistering disease which is a cutaneous manifestation of gluten sensitivity
Associated with Celiac disease, but severe skin disease does not necessarily mean severe GI disease
How does dermatitis herpetiformis (DH) appear? Are they itchy? Where are the lesions most often found?
Intensely pruritic clusters of vesicles or excoriations (often hard to find vesicles since they are so itchy)
-> grouped together like herpes “herpetiform”
Lesions often found on extensor surfaces such as elbows and knees
What will skin biopsy of DH show via H&E and direct immunofluorescence?
H&E - neutrophilic infiltrate of papillary dermal tips
DIF - granular IgA deposition
What antibodies are positive in DH vs celiac disease which correlate with disease severity?
Dermatitis herpetiformis - Epidermal tissue transglutaminase (TG-3)
Celiac disease - tissue transglutaminase-2 (TG-2) / anti-endomysial antibody (same thing)
-> if present, is a good confirmatory test for DH
What are the two treatments for dermatitis herpetiformis and their mechanisms of action in this disease?
- Strict gluten free diet
2. Oral dapsone -> inhibits myeloperoxidase
What is the most common autoimmune blistering disease of the skin? Who tends to get it? What causes it and what will form?
Bullous pemphigoid - tends to happen in elderly patients
Caused by IgG antibodies against hemidesmosomes
-> formation of tense bullae
What are the autoantibodies of bullous pemphigoid and how do you remember their location?
Anti BP180 (BPA2) and anti BP230 (BPA1, discovered first)
- > subepidermal because they are “bullow” the epidermis
- > hooks basal epithelial cells into basement membrane
What is the Nikolsky sign for Bullous pemphigoid?
Negative. That is, firm pressure on normal skin will not induce a blister
-> skin still has good structural integrity
What will skin biopsy show by direct immunofluoresence and H&E?
H&E: Subepidermal bulla with infiltrate of eosinophils
DIF: Linear IgG deposition alone epidermal basement membrane zone
What are lesions in BP and what area is spared?
Symmetrical lesions on trunk and flexual aspects of limbs
Oral mucosa is spared (vs pemphigus vulgaris)
How does indirect immunofluorescence work for detecting anti-BP180/230 antibodies?
Incubate monkey esophagus with patient’s serum. Add secondary antibody to patient’s autoantibody, which will light up with fluorescein tag.
What medications may cause bullous pemphigoid?
Furosemide, penicillins
What medications can be used to treat bullous pemphigus?
Systemic steroids, ultrapotent topical steroids.
Tetracyclines + niacinamide (antinflammatory niacin derivative which causes less flushing)
Systemic immunosuppressives.
What is the cause of pemphigus vulgaris and who tends to get it?
IgG antibodies against desmogleins (component of desmosomes)
Tends to be in adults 50-60, slightly younger than bullous pemphigoid
What type of lesions does pemphigus vulgaris cause and will there be scarring?
Causes flaccid blisters that rupture easily leaving superficial erosions
- > this is due to loss of intraepidermal integrity
- > erosions last for weeks but heal WITHOUT scarring (defect is very superficial).
Where will lesions appear, and what two signs are characteristically positive in pemphigus vulgaris?
Lesions appear anywhere where there’s skin, as well as in ORAL MUCOSA (vs BP)
- Nikolsky’s sign + - firm pressure / rubbing on normal skin will induce a blister
- Asboe-Hansen sign+ - Lateral pressure on intact bullae causes the fluid to dissect laterally into adjacent normal appearing skin
What will DIF and H&E show for pemphigus vulgaris?
DIF - reticular pattern of immune complex deposition around keratinocytes (affecting stratum spinosum)
H&E - “tombstone appearance”, as basal cells remain attached to basement membrane by hemidesmosomes, but rest of epidermis is lifted off
What is acantholysis?
Separation of keratinocytes, seen in pemphigus vulgaris, due to loss of cell-cell adhesion.
Acanthosis would be a hyperproliferation of keratinocytes
What medications are thought to worsen pemphigus vulgaris?
ACE inhibitors (i.e. captopril), chelators (i.e. penicillamine)
How is pemphigus vulgaris typically treated?
Systemic steroids are the mainstay. Steroid sparing immunosuppressive agents (i.e. MTX, AZA) are often needed in order to taper steroids.
What is the typical presentation of your average lupus rash? Do they scar?
Superficial and indurated (hardened) red to purple plaques on sun exposed chest, shoulders, and dorsal hands
They typically resolve without scarring
What is the mnemonic for lupus symptoms?
SOAP BRAIN MD
Remember than BRAIN is describing systemic signs and symptoms, and MD is describing the rash
Serositis
Oral ulcers
Arthritis
Photosensitivity
Blood/hematologic (AIHA / antiphosphlipid syndromes)
Renal
ANA positive
Immunologic/serologies (ANA,anti-smith,dsDNA)
Neurologic (seizures, psychosis)
Malar rash
Discoid rash
What is the pattern of rash in acute cutaneous lupus erythematosus (ACLE)? Include how this is told apart from rosacea and dermatomyositis
Rash is erythematous macules to edematous plaques.
Up to 50% have butterfly rash which SPARES nasolabial folds (indicates photosensitive, vs rosacea)
Oral ulcerations may accompany acute eruption
Rash tends to appear on sun exposed chest, shoulder, and dorsal hands but SPARES the nuckles (vs dermatomyositis)
What workup should be done for ACLE?
ANA, anti-dsDNA, anti-SM
CBC, CR/BUN, careful ruling out of evidence of internal disease in this acute presentation
What drugs are commonly associated with drug-induced lupus?
Hydralazine, isoniazid (lupus wolf next to lone ranger), procainamide (lupus wolf next to prom king), methyldopa, minocycline, quinidine, chlorpromazine, phenytoin /carbamazepine
What antibody is characteristic of drug-induced lupus?
anti-histone antibody
What drugs are used in the treatment of SLE? Give the mechanism of action of the antimalarial that’s used.
- Systemic steroids (i.e. prednisone)
- Immunosuppressants (i.e. MTX)
- Hydroxychloroquine (reduces chemotaxis, phagocytosis, and superoxide production in PMNs by disrupting lysosomes)
What is the clinical distribution of the rash in subacute cutaneous lupus erythematosus (SCLE)?
Sun exposed skin of upper back, chest, shoulders, and proximal extremities. Rash is very RARE below the waist. Malar rash is also rarely present.
What does the rash of subacute cutaneous lupus erythematosus look like and what is on the differential?
Looks like annular or polycyclic plaques with what scaling / crust. Often with an area of central hypopigmentation
Must be differentiated from tinea corporis which is also annular, psoriasis, and dermatomyositis
What labs are typically elevated in SCLE and what is the most common cause?
Typically anti-Ro (SS-A) or anti-La (SS-B) antibodies from Sjogren’s syndrome.
Usually drug-induced and may progress to systemic disease.
Common causes: HCTZ, calcium channel blockers, ace-inhibitors, terbinafine and griseofulvin
Why are pregnant mothers at risk if they have SCLE?
Anti-Ro antibodies may transfer across the placenta (Ro Ro Ro your boat) and cause neonatal lupus
-> congenital heart block requiring pacemaker as well as raccoon eyes in neonates are common manifestations
What is the most common form of cutaneous lupus? Does is it accompanied by systemic disease?
Discoid Lupus Erythematosus (DLE)
Only progresses to systemic disease in about 5% of cases
What do DLE lesions look like and where do they appear? What can they lead to (this is unique)?
Erythematous plaques with firmly adherent scaling and follicular plugging.
- > can lead to central atrophy, SCARRING, and even irreversible alopecia due to destruction of hair follicles
- > only form of lupus rash which scars
Scalp (->alopecia), face, and ears are very common places
How is DLE told apart from psoriasis? What lesion is pathognomonic of DLE?
DLE is more photosensitive than psoriasis, and psoriasis often spares the face
Discoid lesions can occur in SLE as well.
Pathognomonic - Conchal bowl involvement (inside the ear)
What is another name for small vessel vasculitis in clinical practice?
Cutaneous leukocytoclastic vasculitis (LCV) - damage is due to invasion of neutrophils in and around vessels
Where do the cutaneous manifestations of small vessel vasculitis typically appear and what do the lesions look like?
Classical on lower extremities and buttocks
- > purpuric macules, papules, and vesicles, sometimes with areas of central necrosis
- > purpuric papules are called ‘palpable purpura’
Where does IgA tend to deposit in the blood vessels and kidneys in Henoch-Schonlein Purpura?
Skin - postcapillary venules, due to where the most venous stasis occurs. This is where IgA antibodies can bind vessel walls.
Kidneys - mesangial deposition (Berger disease = IgA nephropathy)
How does the internal involvement of HSP present?
GI involvement - abdominal pain, bleeding (guaiac stool test should be done), bowel perforation
Renal involvement - microscopic or gross hematuria (nephritic syndrome)
Joints - painful arthritis
