Autoimmune Disease of the Skin

Question 1

What is dermatitis herpetiformis? What condition is it associated with and how does it correlate with disease activity?

Answer 1

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

Question 2

How does dermatitis herpetiformis (DH) appear? Are they itchy? Where are the lesions most often found?

Answer 2

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

Question 3

What will skin biopsy of DH show via H&E and direct immunofluorescence?

Answer 3

H&E - neutrophilic infiltrate of papillary dermal tips

DIF - granular IgA deposition

Question 4

What antibodies are positive in DH vs celiac disease which correlate with disease severity?

Answer 4

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

Question 5

What are the two treatments for dermatitis herpetiformis and their mechanisms of action in this disease?

Answer 5

1. Strict gluten free diet

2. Oral dapsone -> inhibits myeloperoxidase

Question 6

What is the most common autoimmune blistering disease of the skin? Who tends to get it? What causes it and what will form?

Answer 6

Bullous pemphigoid - tends to happen in elderly patients

Caused by IgG antibodies against hemidesmosomes
-> formation of tense bullae

Question 7

What are the autoantibodies of bullous pemphigoid and how do you remember their location?

Answer 7

Anti BP180 (BPA2) and anti BP230 (BPA1, discovered first)

• > subepidermal because they are “bullow” the epidermis
• > hooks basal epithelial cells into basement membrane

Question 8

What is the Nikolsky sign for Bullous pemphigoid?

Answer 8

Negative. That is, firm pressure on normal skin will not induce a blister
-> skin still has good structural integrity

Question 9

What will skin biopsy show by direct immunofluoresence and H&E?

Answer 9

H&E: Subepidermal bulla with infiltrate of eosinophils

DIF: Linear IgG deposition alone epidermal basement membrane zone

Question 10

What are lesions in BP and what area is spared?

Answer 10

Symmetrical lesions on trunk and flexual aspects of limbs

Oral mucosa is spared (vs pemphigus vulgaris)

Question 11

How does indirect immunofluorescence work for detecting anti-BP180/230 antibodies?

Answer 11

Incubate monkey esophagus with patient’s serum. Add secondary antibody to patient’s autoantibody, which will light up with fluorescein tag.

Question 12

What medications may cause bullous pemphigoid?

Answer 12

Furosemide, penicillins

Question 13

What medications can be used to treat bullous pemphigus?

Answer 13

Systemic steroids, ultrapotent topical steroids.

Tetracyclines + niacinamide (antinflammatory niacin derivative which causes less flushing)

Systemic immunosuppressives.

Question 14

What is the cause of pemphigus vulgaris and who tends to get it?

Answer 14

IgG antibodies against desmogleins (component of desmosomes)

Tends to be in adults 50-60, slightly younger than bullous pemphigoid

Question 15

What type of lesions does pemphigus vulgaris cause and will there be scarring?

Answer 15

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).

Question 16

Where will lesions appear, and what two signs are characteristically positive in pemphigus vulgaris?

Answer 16

Lesions appear anywhere where there’s skin, as well as in ORAL MUCOSA (vs BP)

1. Nikolsky’s sign + - firm pressure / rubbing on normal skin will induce a blister
2. Asboe-Hansen sign+ - Lateral pressure on intact bullae causes the fluid to dissect laterally into adjacent normal appearing skin

Question 17

What will DIF and H&E show for pemphigus vulgaris?

Answer 17

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

Question 18

What is acantholysis?

Answer 18

Separation of keratinocytes, seen in pemphigus vulgaris, due to loss of cell-cell adhesion.

Acanthosis would be a hyperproliferation of keratinocytes

Question 19

What medications are thought to worsen pemphigus vulgaris?

Answer 19

ACE inhibitors (i.e. captopril), chelators (i.e. penicillamine)

Question 20

How is pemphigus vulgaris typically treated?

Answer 20

Systemic steroids are the mainstay. Steroid sparing immunosuppressive agents (i.e. MTX, AZA) are often needed in order to taper steroids.

Question 21

What is the typical presentation of your average lupus rash? Do they scar?

Answer 21

Superficial and indurated (hardened) red to purple plaques on sun exposed chest, shoulders, and dorsal hands

They typically resolve without scarring

Question 22

What is the mnemonic for lupus symptoms?

Answer 22

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

Question 23

What is the pattern of rash in acute cutaneous lupus erythematosus (ACLE)? Include how this is told apart from rosacea and dermatomyositis

Answer 23

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)

Question 24

What workup should be done for ACLE?

Answer 24

ANA, anti-dsDNA, anti-SM

CBC, CR/BUN, careful ruling out of evidence of internal disease in this acute presentation

Question 25

What drugs are commonly associated with drug-induced lupus?

Answer 25

Hydralazine, isoniazid (lupus wolf next to lone ranger), procainamide (lupus wolf next to prom king), methyldopa, minocycline, quinidine, chlorpromazine, phenytoin /carbamazepine

Question 26

What antibody is characteristic of drug-induced lupus?

Answer 26

anti-histone antibody

Question 27

What drugs are used in the treatment of SLE? Give the mechanism of action of the antimalarial that’s used.

Answer 27

1. Systemic steroids (i.e. prednisone)
2. Immunosuppressants (i.e. MTX)
3. Hydroxychloroquine (reduces chemotaxis, phagocytosis, and superoxide production in PMNs by disrupting lysosomes)

Question 28

What is the clinical distribution of the rash in subacute cutaneous lupus erythematosus (SCLE)?

Answer 28

Sun exposed skin of upper back, chest, shoulders, and proximal extremities. Rash is very RARE below the waist. Malar rash is also rarely present.

Question 29

What does the rash of subacute cutaneous lupus erythematosus look like and what is on the differential?

Answer 29

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

Question 30

What labs are typically elevated in SCLE and what is the most common cause?

Answer 30

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

Question 31

Why are pregnant mothers at risk if they have SCLE?

Answer 31

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

Question 32

What is the most common form of cutaneous lupus? Does is it accompanied by systemic disease?

Answer 32

Discoid Lupus Erythematosus (DLE)

Only progresses to systemic disease in about 5% of cases

Question 33

What do DLE lesions look like and where do they appear? What can they lead to (this is unique)?

Answer 33

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

Question 34

How is DLE told apart from psoriasis? What lesion is pathognomonic of DLE?

Answer 34

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)

Question 35

What is another name for small vessel vasculitis in clinical practice?

Answer 35

Cutaneous leukocytoclastic vasculitis (LCV) - damage is due to invasion of neutrophils in and around vessels

Question 36

Where do the cutaneous manifestations of small vessel vasculitis typically appear and what do the lesions look like?

Answer 36

Classical on lower extremities and buttocks

• > purpuric macules, papules, and vesicles, sometimes with areas of central necrosis
• > purpuric papules are called ‘palpable purpura’

Question 37

Where does IgA tend to deposit in the blood vessels and kidneys in Henoch-Schonlein Purpura?

Answer 37

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)

Question 38

How does the internal involvement of HSP present?

Answer 38

GI involvement - abdominal pain, bleeding (guaiac stool test should be done), bowel perforation

Renal involvement - microscopic or gross hematuria (nephritic syndrome)

Joints - painful arthritis