Derm E2: hypersensitivity/autoimmune/rheum etc

What is urticaria (hives)?

edema w/in cutaneous vascular plexus of papillary body

caused by: insect bites, stings, meds, foods, infx

what are clinical features of urticaria?

• transient pruritic edematous papules and plaques

• superficial and well defined

• can be assoc. w/ angioedema

• location: face, lips, trunk, extremities

• acute: < 6 wks, IgE dependent

• chronic: > 6 wks

What are risk factors for urticaria?

atopy

What is the pathophysiology of urticaria?

• mast cell degranulation → release immune mediators (histamine, prostaglandins, leukotrienes, cytokines, chemokines)

• induce vasodilation and inc permeability of vessels → dermal edema

what type of hypersensitivity is acute urticaria?

type 1; IgE mediated

what type of hypersensitivity is chronic urticaria?

type 2-4

what is dermographism / urticaria factitia?

linear urticarial lesions after stroking/scratching skin; < 30 min

what is cold urticaria?

lesions confined to sites exposed to cold; special test- ice cube test

what is solar urticaria?

post solar exposure

what is cholinergic urticaria?

exercise and sweating → small, papular, highly pruritic urticarial lesions; special test- treadmill test

what is contact urticaria?

contact with water → eruption similar to cholinergic urticaria

What are autoimmune dz that urticaria is assoc. w/?

SLE, sjogrens dz, thyroid disorders, RA, DMT1

lesions persist for 12-24 hrs

what is urticarial vasculitis?

2 elements: urticaria (> 24 hrs) and histopathology confirming leukocytoclastic vasculitis of small vessels

assoc. w/ hypocomplementemia

what is tx for urticaria?

• H1 receptors

  • 1st gen: hydroxyzine (atarax), diphenhydramine (Benadryl)

  • 2nd gen: loratadine (Claritin), cetirizine (zyrtec), fexofenadine (allegra) *less sedating

• oral glucocorticoids- i.e prednisone

what is angioedema?

acute, self limited, localized SC or submucosal swelling, which results from extravasation of fluid into interstitial tissues

location: face, lips, larynx, bowel, genitalia

what are clinical features of angioedema?

• large edematous area ± pruritus

• deep and ill defined areas

• occurs w/in hrs and resolves w/in 1-3 days

• pressure: delayed, painful, erythematous swelling induced by sustained pressure

• vibratory: caused by vibrating stimulus

what are classifications of angioedema?

histaminergic (allergic): assoc. w/ anaphylaxis

non-histaminergic: can present w/ urticaria

drug induced: ACE inhibitors

C1 inhibitor deficiency: autosomal dominant hereditary; affects face, extremities, laryngeal edema, angioedema of bowel

idiopathic

what is the pathophysiology of angioedema?

• mast cell mediated: release of mast cells derived mediators that inc vascular permeability

  • assoc. w/ pruritus and urticaria

  • begins w/in mins and resolves over 24-48 hrs

• bradykinin mediated: overproduction or inhibition of bradykinin degradation resulting in vascular permeability and vasodilation

  • pruritus and urticaria are absent

  • frequently involves GI muse → bowel wall edema

  • develops over 24-36 hrs and resolves over 2-4 days

what is tx of angioedema?

• evaluate in ER

• w/ airway involvement → protect airway

• w/ anaphylaxis → epi IM or IV, IVFs, oxygen

• allergic → antihistamines and glucocorticoids are mainstay, ex- methylprednisolone (solumedrol) 600-80mg IV bolus

What is behcet syndrome?

rare vasculitis characterized by recurrent aphthous ulcers of mouth, eyes, skin, GI dz, CNS involvement, and arthritis

exact cause unknown, linked to genetics and infectious exposure

what are clinical features of behcet syndrome?

• recurrent, mucocutaneous aphthous ulcers

• genital ulcers- found ons scrotum In men and vulva in women

• cutaneous lesions- acneiform, papulovesicular eruptions, nodules, thrombophlebitis, palpable purpura

• location: mouth, genital, ocular, GI, CNS, vascular, arthritis

what are risk factors for behcet syndrome?

M > F

what are complications of behcet syndrome?

• pulmonary artery aneurysms

• CNS dz

• vasculitis including all arteries and veins

• ocular dz → uveitis → blindness

How do you dx behcet syndrome?

clinical; recurrent oral aphthae atleast 3x in 1 yr) plus 2 of the following

• recurrent genital aphthae (aphthous ulceration or scarring)

• eye lesions (including anterior/posterior uveitis

• skin lesions

• positive pathergy test

what is tx for behcet syndrome?

aphthous and genital ulcers: 1st line→ TCS ± topical sucralfate

recurrent ulcers: colchicine 1-2mg/day divided BID

refractory lesions: prednisone or azathioprine

what is dermatomyositis?

idiopathic inflammatory myopathy that commonly presents w/ progressive, symmetric, proximal muscle weakness and a group of cutaneous findings

unknown cause

what are clinical features of dermatomyositis?

• progressive, symmetric proximal muscle weakness

• gottrons papules: pink violaceous papules overlying interphalangeal and metacarpophalangeal joints

• heliotrope eruption: pink violaceous erythema, ± edema, involving periorbital skin

• shawl sign: confluent, violaceous erythema on posterior neck, upper back, and shoulders

• rash is photosensitive

what is the pathophysiology of dermatomyositis?

thought to be result of humoral mediated attack against muscle capillaries and arteriole endothelium

hypoxic injury to muscle fibers ensues, leading to atrophy of muscle fibers

what are risk factors of dermatomyositis?

age < 55, genetics, viral exposure (coxsackie, parvovirus, HIV), meds

how do you dx dermatomyositis?

skin bx: vacuolar changes of basal layer, inc lymphocytic infiltrate, and inc mucin deposition in dermis

muscle bx: perivascular inflammatory infiltrate, atrophy of muscle fibers in perifascicular region, IG and complement deposits on intramuscular blood vessels

creatine kinase

aldolase levels

LDH

ANA, anti-mi-2, anti-jo antibodies

what is 1st line tx for dermatomyositis?

systemic glucocorticoids (ie prednisone) ± DMARD (ie MTX)

alt for skin dz: hydroxychloroquine plus MTX

what is 2nd line tx of dermatomyositis?

rituximab, mycophenolate, IVIG

what is patient education for dermatomyositis?

• educate on using SPF

• for pruritus→ antihistamines, TCS, or calcineurin inhibitors

• all pts should have screening CXR to eval for interstitial lung dz

• maintain high protein diet and physical exercise to inc muscle strength

what is cutaneous lupus erythematous?

chronic autoimmune dz that encompasses a wide range of dermatologic manifestations and may or may not be assoc. w/ systemic dz

what are the 3 subsets of cutaneous lupus erythematous?

acute (ACLE): transient erythematous patches

subacute (SCLE): small erythematous scaly papules

chronic (CCLE): subtypes discoid (DLE) and lupus panniculitis

what are vascular manifestations of CLE?

periungual erythema: dilated tortuous loops of caps and prominent sub cap venous plexus along base of nail

livedo reticularis: reddish-cyanotic, reticular pattern on skin- arms, legs, torso (exacerbated by cold temps)

Raynaud phenomenon: vasospastic process of fingers/toes → blanching

vasculitis: urticarial vasculitis → painful petechial or purpura that may heal w/ hyperpigmentation

what is acute cutaneous lupus erythematous (ACLE)?

• malar or butterfly rash: erythema along cheeks and bridge of nose; spares nasolabial folds; may last hrs-wks; exacerbated by sun exposure

• morbilliform rash: erythematous maculopapular eruption on sun exposed areas

• histology: apoptotic keratinocytes, vascuolization of basal cell layer; lymphohistiocytic infiltrate in superficial dermis and dermic mucin deposition

What is subacute cutaneous lupus erythematosis (SCLE)?

• small, erythematous, slightly scaly papules that evolve into either psoriasiform or annular plaques

• location: shoulders, forearms, neck, upper torso

• risk: sun exposure, drug induced (anticonvulsants, ACEI, BBs, immune modulators)

• histology: superficial perivascular and appendageal lymphocytic infiltration; vascuolization of basement membrane and mucin deposition in dermis

what is the MC type of CCLE?

discoid lupus

what is chronic cutaneous lupus erythematosus (CCLE?)

• discrete, erythematous, indurated plaques covered by well-formed adherent scale that extends into dilated hair follicles

• plaques heal leaving depressed central scars, atrophy, telangiectasis, and hyper or hypopigmentation

• location: face, neck, scalp, ears, upper torso

• histology: hyperkeratosis, follicular plugging, basal layer vacuole changes and mononuclear cell infiltrate at DEJ

what is lupus panniculitis / lupus profundus?

• presents as painful indurates plaques or firm SC nodules

• upon resolution → SC atrophy and scarring

• location: scalp, face, upper arms, chest, breasts, lower back, flank, upper thighs, or buttocks

what are risk factors for CLE?

African American; F > M

how do you dx CLE?

biopsy, labs, ANA postive (>95%)

what is 1st line tx for CLE?

photoprotection: broad spectrum sunscreen

topical vs intralesional vs oral corticosteroids

refractory: oral antimalarials (hydroxycloroquine or chloroquine)

what is 2nd line tx for CLE?

glucocorticoid-sparing DMARDs→ MTX

what is scleroderma?

hallmark feature of systemic sclerosis; widespread vascular dysfunction and progressive fibrosis of skin and internal organs

what are clinical features of scleroderma?

• pruritus and edema in early stages

• skin hyperpigmentation or depigmentation

• dry skin, skin thickening/hardening

• Raynaud phenomenon

• painful ulcerations at DIP/PIP ; “rat bite necrosis”

• sclerodactyly w/ tapering of fingers→ loss of distal phalanges

• loss of sweat glands, anhidrosis

• calcinosis cutis

• early face changes→ periorbital edema

• late face changes → edema and fibrosis result in loss of normal facial line, mask like thinning of lips, beak like sharp nose

how do you dx scleroderma?

• ANA- pos

• anticentromere abs (ACA)

• anti-Scl-70 abs

  • extremity plain films- may demonstrate calcinosis

what is tx for scleroderma?

1st line: MTX

refractory: IVIG or Rituximab (Rituxan)

what is the mnemonic for scleroderma associated syndrome?

CREST syndrome

Calcinosis cutis- fingertips, elbows, trochanteric regins

Raynaud phenomenon

Esophageal dysfunction- dysphagia, diminished peristalsis, reflux esophagitis

Sclerodactyly

Telangiectasia- face, upper trunk, handsw

what is Raynaud phenomenon?

exaggerated vascular response to cold temps or emotional stress

what are the subtypes of Raynaud phenomenon?

primary RP: exaggeration of vasoconstriction to cold temp w/o underlying dz; 15-30 y/o and MC in females

secondary RP: vasoconstriction occurs due to underlying dz

what are clinical features of Raynaud phenomenon?

• digital color changes

  • white pallor- vasoconstriction

  • blue- tissue hypoxia

  • red- reperfusion after rewarming

• numbness/pain

• cold induced skin color changes

what are risk factors for RP?

F > M, cold temp, stress, smoking, underlying dz

what is nonpharmacologic management of RP?

smoking cessation, avoid cold exposure, hand warmers, avoid vasoconstrictive meds (pseudoephedrine, amphetamines, sumatriptan)

what is pharmacologic management for RP?

1st line: Ca channel blockers; Amlodipine, Nifedipine

2nd line: PDE5I or topical nitrate; sildenafil PO or nitroglycerin 2% cream

what is IGA vasculitis / henoch schoenlein purpura?

acute IgA mediated vasculitis involving small vessels of skin, GI tract, kidneys, joints, and rarely lungs and CNS

what are clinical features of IgA vasculitis / HSP?

• palpable purpura in pts w/ neither thrombocytopenia nor coagulopathy

  • can be pruritic, rarely painful

  • rash begins as erythematous macular or urticarial wheals and progresses to petechia and palpable purpura

• arthritis/arthralgia

• abd pain- can be assoc. w/ GI bleeding

• renal dz

• location- lower extrem, lesions appear symmetrical in crops

what are risk factors for HSP?

age bt 4-7; infx- s. pyogenes

how do you dx HSP?

labs: CBC, CMP, PT/INR, PTT

skin bx: pathognomic finding- leukocytoclastic vasculitis in post capillary venues w/ IgA deposition

What is tx for HSP?

majority recover spontaneously

supportive- pain control (acetaminophen and NSAIDs)

hospitalization if severe dehydration, GI bleeding, mental status change, elevated BUN/cr

what is polyarteritis nodosa?

systemic necrotizing vasculitis that typically affects medium sized muscular arteries, w/ additional involvement of small arteries

cause- idiopathic

what are clinical features of polyarteritis nodosa?

• assoc. w/ constitutional sx- fever, fatigue, malaise, arthralgias, loss of appetite

• skin lesions- purpura, livedo reticularis, painful nodules, ulcers follow ischemia of nodules

• location: lower legs, thighs, arms, trunk, head, neck, buttocks

• risk: male and age

how do you dx polyarteritis nodosa?

ANCA, ANA, complement proteins, skin bx

what is tx for polyarteritis nodosa?

mild: prednisone

moderate-severe: combo therapy- azathioprine or MTX

what is Kawasaki dz?

self limiting vasculitis of childhood

what are clinical features of Kawasaki dz?

• fever

• cutaneous/mucosal erythema and edema w/ subsequent desquamation

• bilateral non exudative conjunctivitis

• polymorphous exanthem

• cervical LAD

• cracked, cherry red lips and oropharyngeal erythema

• erythema of palms/soles

what are risk factors for Kawasaki dz?

age- 2.5 y/o***; winter/spring seasons

what are complications of Kawasaki dz?

coronary abnormalities → coronary artery aneurysm, myocarditis, arthritis, urethritis, aseptic meningitis

how do you dx Kawasaki dz?

presence of fever lasting atleast 5 days w/o explanation PLUS 4 out of the 5 following:

• bilateral bulbar conjunctival injection

• oral mucous membrane changes, including injected or fissured lips, injected pharynx, or strawberry tongue

• peripheral extremity changes including erythema of palms/soles, edema of hands/feet (acute phase), and periungual desquamation (convalescent phase)

• polymorphous rash

• cervical LAD

what is the dx workup for Kawasaki dz?

LFTs- elevated

CBC- leukocytosis, thrombocytosis, anemia

ESR- elevated or normal

U/A- pyuria

echo- eval for coronary aneurysm

what is tx for Kawasaki dz?

IVIG 2g/kg infused over 8-12 hrs

ASA 30-50 mg/kg/daily divided every 6 hrs

what is sarcoidosis?

systemic granulomatous dz of unknown cause

what are clinical features of subtypes of sarcoidosis?

papular: papules, translucent yellow-red w/ apple jelly appearance on diascopy

nodular: erythema nodosum

lupus pernio: diffuse, violaceous, soft doughy infiltrations on nose, cheeks, or earlobes

plaque: brown or purple infiltrated plaques- mainly on extremities, buttocks, and trunk

maculopapular: scattered maculopapular lesions yellow/brow/purple one ace and extremities

subcutaneous: erythematous, flesh colored, violaceous, or hyperpigmented nodules

what are risk factors for sarcoidosis?

African American

how do you dx sarcoidosis?

diascopy: apply jelly semi translucent yellowish brown color

skin or LN bx: noncaseating granuloma

what is tx for sarcoidosis?

localized: intralesional or topical steroids (class I-II)

systemic: oral glucocorticoids

refractory: MTX, hydroxycholorquine

what is another name for granulomatosis w/ polyangiitis (GPA)?

wegener granulomatosis

what is GPA?

rare autoimmune necrotizing vasculitis affecting small sized arteries

unknown cause

what are clinical features of GPA?

• purpura w/ focal necrosis

• oral/nasal ulcerations

• skin ulcers

• papules, vesicles, palpable purpura

• triad:

  • necrotizing granuloma in upper resp. tract and lungs

  • vasculitis involving both arteries and veins

  • glomerulitis

• location: lower limbs, face, trunk, upper extremities

what are complications of GPA?

renal failure, interstitial lung dz

How do you dx GPA?

CBC: anemia, leukocytosis, ± thrombocytosis

ESR elevated

impaired renal function

urine: RBC casts

antineutrophil cytoplasmic autoabs (ANCA), C3, C4, ANA

skin bx: necrotizing vasculitis of small arteries/vein w/ intra or extravascular granuloma formation

what is tx for GPA?

induction: cyclophosphamide or rituximab PLUS prednisone

maintenance: MTX or rituximab or azathioprine

prevention of opportunistic infx: trimethoprim (Bactrim) 160-800 mg 3x/weekly

what is bullous pemphigoid?

autoimmune chronic inflammatory sub epidermal blistering dz

cause: hypothesized destruction and inflammation caused by IG binding in epithelial basement membrane zone

what are clinical features of bullous pemphigoid?

• prodromal: wks/mos of pruritic eczematous papular or urticaria like skin lesions

• 1-3 cm bulla on erythematous, urticarial, noninflammatory base; blisters may be numerous and widespread

• pruritus

  • location: trunk, extremity flexures, axillary/inguinal folds, oral mucosa, larynx, genital and anus

what are risk factors for bullous pemphigoid?

age > 60

how do you dx bullous pemphigoid?

• clinical- should be suspected in pts > 60 w/ features of

  • blistering skind z

  • desquamative gingivitis or mucositis

  • unexplained pruritic urticarial plaques

• skin bx- definitive

what is tx for bullous pemphigoid?

• initial tx: one of the following

  • high potency TCS- clobetasol

  • oral glucocorticoids

  • doxycycline

• refractory: biologics- ritximab (rituxan)

what is pemphigus vulgaris?

rare autoimmune dz characterized by painful blisters and erosions on skin and mucous membranes; MC bt ages 40-60

what are clinical features of pemphigus vulgaris?

• intraoral blisters and erosions

• cutaneous lesions- vesicles, erosions, bullae

• pos nikolsky sign

• heals w/o scarring

• location: mouth (MC), genitalia, face, scalp, trunk, groin, axilla

what is pathophysiology of pemphigus vulgaris?

autoantibodies against desmoglzins → disrupts keratinocyte adhesion causing separation → acantholysis

(desmogleins are glycoproteins that are required for cell-cell adhesion)

how do you dx pemphigus vulgaris?

skin bx- acantholytic cells above basal layer of epidermis

ELISA test- look for anti-desmoglein abs

what is tx for pemphigus vulgaris?

1st: systemic corticosteroids (prednisone); add rituximab in mod-severe cases

2nd: immunosuppressive drugs (azathioprine, MMF)

what is erythema nodosum?

delayed type hypersensitivity rxn that most often presents as erythematous, tender nodules on shins

what are clinical features of erythema nodosum?

• prodrome: fever, fatigue, malaise, arthralgias may precede nodules 1-3 wks

• erythematous, tender, non ulcerated nodules 2-5 cm

• location: shins, ankles, thighs, arms, buttocks, calves, face

what are risk factors for erythema nodosum?

drugs, pregnancy malignancy, strep infx, inflammatory conditions (sarcoidosis, GI dz, IBD)

how do you dx erythema nodosum?

clinical; assess for underlying cause- CBC, ESR, ASO titer, CXR

what is tx for erythema nodosum?

mild: elevate legs, rest, compression

moderate: NSAID- ibuprofen, naproxen

severe: oral glucocorticoid- prednisone, intralesional steroid injection

what is neurofibromatosis?

multi system genetic disorder most notably characterized by cafe au lait spots and neurofibromas

autosomal dominant inheritance

what are clinical features of neurofibromatosis?

• multiple cafe au lait spots

• soft, fleshy, sessile, pedunculated tumors

• freckling- axillary/inguinal regions

• Lisch nodules: raised tan colored hamartomas of iris

• location: trunk

• subtypes

  • NF1- von recklinghausen

  • NF2- schwannomatosis