Vascular Diseases




(1)
Department of Dermatology, University of Pennsylvania, Penn Presbyterian Medical Center Medical Arts Building, Philadelphia, PA, USA

 



5.1 Toxic Erythema

5.1.1 Viral Exanthems (Children > > Adults)

5.1.2 Drug Eruptions (Adults > > Children)

5.1.3 Scarlatiniform Eruptions

5.1.4 Other Reactive Toxic Erythema

5.2 Figurate Erythemas (Annular or Gyrate Erythemas)

5.3 Urticaria

5.4 Erythema Multiforme (EM)

5.5 Purpura

5.5.1 Palpable Purpura/Vasculitis

5.5.2 Macular Purpura

5.5.3 Vasculopathy

5.6 Regional Erythema

5.7 Vascular Tumors

5.8 Other


Abstract

Vascular diseases are mostly dermal because the skin’s blood vessels are in the dermis. They are distinguished from other dermal diseases (other inflammatory, depositional, neoplastic), by their red and purple colors caused by vasodilatation, extravasated red blood cells, and vascular inflammation.


Keywords
Viral exanthemsDrug eruptionsErythema multiformeVasculitis



5.1 Toxic Erythema



5.1.1 Viral Exanthems (Children > > Adults)






  • Path = vasodilatation +/− sparse perivascular infiltrate (same as morbilliform drug eruption)

    (a)

    Classic childhood exanthems

    I.

    First Disease – rubeola/measles – paramyxovirus

     

    II.

    Second Disease – scarlet fever – Streptococcus pyogenes (not viral)

     

    III.

    Third Disease – rubella – togavirus

     

    IV.

    Fourth Disease – “Duke’s disease” – not specific

     

    V.

    Fifth Disease – erythema infectiosum – parvovirus B19

     

    VI.

    Sixth Disease – roseola/exanthem subitum – HHV-6/7

     

    VII.

    Others

    1.

    Gianotti-Crosti syndrome



    • Aka papular acrodermatitis of childhood


    • Typically symmetric papular eruption of extremities, face, and buttocks


    • Usually spares trunk (does not exclude)


    • Associated with EBV, HBV

     

    2.

    Unilateral laterothoracic exanthem



    • Ddx Gianotti-Crosti, often starts in axilla


    • Aka asymmetric periflexural exanthem of childhood (APEC)


    • Unclear etiology

     

    3.

    Varicella (chickenpox)



    • See also Infectious Diseases:Viral

     

     

     

    (b)

    Other viral exanthems



    • Classically associated with enteroviruses


    • Acute HIV seroconversion (classic morbilliform) (see also Infectious Diseases:Viral)


    • Pityriasis rosea thought perhaps to be a viral exanthem from HHV-6 or 7 (see also Papulosquamous: Pityriasiform)

     


5.1.2 Drug Eruptions (Adults > > Children)






  • Note: the typical toxic erythema eruption presents a ddx of viral exanthem vs. morbiliform drug eruption. Drug eruptions of any type, beyond that of simple morbilliform eruptions, are also listed here.


(a)

Morbilliform drug eruption



  • Aka exanthematous drug eruption, maculopapular eruption


  • Classically occurs 5–14 days after exposure; commonly from PCN/sulfa/anti-convulsant/allopurinol/cephalosporin


  • Occurs faster upon reexposure


  • Will occur when PCN given for mononucleosis (not an allergy)


  • Thought to be caused by a delayed type IV hypersensitivity reaction


  • Path = vasodilatation +/− sparse perivascular infiltrate (same as viral exanthem)

 

(b)

DRESS (Drug reaction with eosinophilia and systemic symptoms)



  • Aka drug hypersensitivity syndrome (originally called Dilantin hypersensitivity syndrome)


  • Eruption is typically morbilliform, but may have myriad presentations


  • Typically 15–40 days after exposure


  • Most commonly from aromatic antiepileptic agents (phenytoin, carbamazepine, and phenobarbital – these three cross-react), the sulfonamides, allopurinol (especially in setting of renal dysfunction, may be later – 7 weeks), dapsone (dapsone hypersensitivity syndrome), minocycline


  • Predisposed to by epoxide hydrolase deficiency (anti-epileptics), slow acetylators (sulfas), certain HLA types


  • Clinically, facial edema may be hallmark


  • Usually see elevation in transaminases (liver most commonly involved)


  • May see eosinophilia (despite name DRESS, only in ~60 %)


  • May also cause myocarditis, pericarditis, nephritis, pharyngitis


  • Possible role of HHV-6 and 7 has been proposed – some will check HHV-6 viral load when diagnosis in question


  • Monitor TFTs for 12 weeks; hypothyroidism possible


  • 10 % mortality, mostly from hepatic necrosis

 

(c)

Serum-sickness-like eruption



  • Fever, arthralgias, urticarial or morbilliform rash


  • Can occur 1–3 weeks after cefaclor most commonly

 

(d)

Drug-induced urticaria/angioedema



  • Most common cause of anaphylaxis: ASA


  • See also Vascular: Urticaria

 

(e)

Drug-induced vasculitis



  • See also Vascular: Purpura: Vasculitis


  • ANCA-associated vasculitis can be induced by PTU

    (propylthiouracil), methimazole, hydralazine, minocycline, levamisole

 

(f)

Erythroderma



  • See also Papulosquamous: Erythroderma/exfoliative dermatitis

 

(g)

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), rarely from erythema multiforme major



  • See also Vascular: Erythema Multiforme


  • 5–21 days after exposure

 

(h)

Fixed drug eruption



  • One or a few, round, sharply demarcated erythematous and edematous plaques sometimes with grey, dusky, violaceous hue, central blister


  • Common sites: mouth (lips and tongue), genitalia, face, and acral areas


  • Occurs <48 hours after exposure, but 1–2 weeks after first exposure


  • Can have non-pigmenting variant with pseudoephedrine


  • Can see disseminated fixed drug eruption that could resemble SJS


  • See also Lists: Other Lists: Drug Eruption Mnemonics

 

(i)

Acute generalized exanthematous pustulosis (AGEP)



  • A pustular drug eruption


  • Non-follicular, sterile pustules on erythematous background, may start on face/axilla/inguinal folds, then generalize; ddx pustular psoriasis, candidiasis


  • Often caused by beta-lactams, macrolides, terbinafine


  • <4 days after exposure, non-antibiotics have longer latency period


  • Can be associated with neutrophilia/elevated WBC (18–25), fever


  • Patch testing positive in 80 %


  • Can see upregulated IL-8 (neutrophil chemoattractant)

 

(j)

Linear IgA disease



  • Most commonly from vancomycin


  • See also Vesiculobullous: Subepidermal blisters, Lists: Other Lists: Drug Eruption Mnemonics

 

(k)

Drug-induced bullous pemphigoid



  • See also Vesiculobullous: Subepidermal blisters, Lists: Other Lists: Drug Eruption Mnemonics

 

(l)

Lichenoid drug eruption



  • Most commonly from beta-blockers, ACE-inhibitors, penicillamine, also TNF-α inhibitors


  • See also Papulosquamous: Lichenoid and Lists: Other Lists: Drug Eruption Mnemonics

 

(m)

Drug-induced interstitial granulomatous dermatitis



  • May be drug-induced, e.g. from ACE inhibitors, calcium channel blockers, other


  • Typically occurs after many years on a drug, and may take months-years after drug cessation before resolution (making establishment of a drug association often difficult)


  • See also Dermal: Granulomatous

 

(n)

Pemphigus-like drug eruption



  • Thiol groups in drugs (ACEIs, penicillamine) can mimic desmogleins


  • See also Vesiculobullous: Subepidermal blisters, Lists: Other Lists: Drug Eruption Mnemonics

 

(o)

Drug-induced lupus



  • See also Connective Tissue Diseases: Lupus, Lists: Other Lists: Drug Eruption Mnemonics

 

(p)

Drug-induced acne



  • See also Acneiform Diseases: Acne

 

(q)

Halogenoderma (includes iododerma)



  • From bromides, fluorides, iodides; acneiform or bullous eruption


  • Ddx folliculitis, dimorphic fungal infections, pyoderma gangrenosum, Sweet’s syndrome, pemphigus vegetans

 

(r)

Pseudolymphoma



  • See also Dermal: Lymphocytic and Neoplastic: Lymphomas


  • Reported from anticonvulsants, antipsychotics

 

(s)

Chemotherapy and radiation-induced drug reactions

I.

Acral erythema of chemotherapy



  • Lumped category of many different chemo reactions on hands and feet


  • Includes erythrodysesthesia


  • Aka hand-foot syndrome


  • Often from cytarabine, bleomycin

 

II.

Sweet’s syndrome (acute febrile neutrophilic dermatosis)



  • Can be caused all-trans-retinoic acid (ATRA), G-CSF, or GM-CSF, but drugs only represent <5 % of Sweet’s cases


  • See also Dermal: Inflammatory: Neutrophilic

 

III.

Neutrophilic eccrine hidradenitis



  • Necrosis of eccrine coils with neutrophilic infiltrate


  • Associated especially with cytarabine in AML

 

IV.

Serpentine supravenous hyperpigmentation



  • Local reaction from IV 5-fluorouracil

 

V.

Radiation recall



  • An eruption in previously irradiated area that occurs with a new systemic medication (e.g. methotrexate)

 

VI.

Radiation enhancement



  • An eruption from a medication exacerbated synergistically with radiation

 

 


5.1.3 Scarlatiniform Eruptions




(a)

Scarlet fever



  • Caused by Group A Strep, erythrogenic toxins A, B and C


  • Clinically, see rough sandpaper erythema, strawberry tongue, Pastia’s lines in body folds, axilla, circumoral pallor


  • See also Infectious Diseases: Bacterial

 

(b)

Staphylcoccal Scalded Skin Syndrome (SSSS)



  • See primarily in children < 5


  • Dsg1 affected by Staph toxin (group 2 type 71)


  • Path: granular layer split (unlike apoptotic keratinocytes in TEN)


  • See also Vesiculobullous: Intraepidermal Blisters and Infectious Diseases: Bacterial

 

(c)

Toxic shock syndrome (Staph aureus or Strep pyogenes)

I.

Staph



  • From phage group 1, many types


  • TSST-1, was originally associated with superabsorbent tampons, now not usually

 

II.

Strep



  • From Group A Strep, pyogenic exotoxins 1 and 3


  • See also Infectious Diseases: Bacterial

 

 

(d)

Kawasaki disease (mucocutaneous lymph node syndrome)



  • Dx criteria = high fever (>102 °F) × 5 days plus 4/5 of:


1.

Conjunctivitis

 

2.

Lip/oral changes

 

3.

Hand/foot swelling/erythema

 

4.

Cervical LAD

 

5.

Polymorphous rash (scarlatiniform, urticarial, or EM-like)

 




  • Unknown etiology, likely infectious


  • Early finding: perineal eruption common with early desquamation two days later


  • Must check ECHO to r/o coronary aneurysm


  • May clinically mimic SJS in children


  • Tx = ASA and IVIg

 


5.1.4 Other Reactive Toxic Erythema




(a)

Graft vs. host disease (GVHD)



  • Acute = (<3 months) often like morbilliform drug eruption


  • Chronic = (>100 days) can have lesions resembling lichen planus, sclerotic lesions like lichen sclerosus, morphea, scleroderma, eosinophilic fasciitis, and poikilodermatous changesAcute GVHD typically begins on head/acral sites first




  • Chronic GVHD usually lichenoid (early), sclerodermoid (late)


  • Induced by donor immunocompetent T cells (predominantly CD8+) against host that cannot reject them


  • Affects primarily the liver (cholestatic hepatitis), GI tract (diarrhea), and skin


  • Most often from allogeneic stem cell or bone marrow transplant for leukemia/lymphoma


  • GVHD actually associated with clinical benefit despite morbidity (anti-tumor effects)


  • Severe form can resemble TEN with positive Nikolsky’s


  • Tx = systemic corticosteroids in addition to tacrolimus/cyclosporine/others; also extracorporeal photopheresis (ECP)


  • See also Papulosquamous: Lichenoid and Connective Tissue Diseases: Sclerotic Disease

 

(b)

Eruption of lymphocyte recovery



  • Transient, can have associated fever, but no GI/liver effects


  • Thought to be from the return of immunocompetent lymphocytes to circulation after chemotherapy-induced lymphopenia


  • May be misdiagnosed as acute GVHD

 


5.2 Figurate Erythemas (Annular or Gyrate Erythemas)


Note: Path usually cannot reliably differentiate the figurate erythemas; may see parakeratosis, spongiosis, “tight cuffing” of perivascular lymphs

1.

Erythema migrans (Lyme disease)



  • Ddx Southern tick-associated rash illness (STARI)


  • See also Infectious Diseases: Treponemes and Spirochetes

 

2.

Erythema annulare centrifugum



  • Superficial (trailing scale) and deep types (infiltrated edge)


  • A hypersensitivity reaction


  • May have many different associations, including blue cheese (from mold)


  • See also Papulosquamous: Other

 

3.

Erythema marginatum (rheumatic fever)



  • Rapidly expanding, evanescent rash, in <10 % of patients with rheumatic fever (reactive from Strep)


  • Path: may see interstitial and perivascular neutrophils (unlike other gyrate erythemas)


  • Reticulate erythema ddx: erythema marginatum, Still’s disease, erythema infectiosum (Parvovirus)


  • See also Infectious Diseases: Bacterial

 

4.

Erythema gyratum repens



  • Extremely rare, associated with malignancy


  • “Wood grain” appearance


  • Paraneoplastic most common with lung cancer


  • Rapid migration, up to 1 cm/day


  • See also Neoplasms: Paraneoplastic syndromes

 

5.

Eosinophilic annular erythema



  • A newly described entity, typically in children, may present as a figurate erythema


  • May be a form of Well’s syndrome, see also Dermal: Eosinophilic

 


5.3 Urticaria






  • Individual raised lesion caused by edema and vasodilatation, called “wheal”; may have pale center and surrounding erythema (“flare”); may appear target-like


  • Although of similar etiology, depth of swelling distinguishes urticaria (more superficial), angioedema (deeper in dermis/subq), and anaphylaxis


  • Acute urticaria commonly from drugs, infectious, foods


  • Type I hypersensitivity reaction


  • Path = vasodilatation and edema +/− sparse perivascular infiltrate


  • Acute urticaria defined as < 6 weeks, chronic urticaria ≥ 6 weeks


  • Often caused by: idiopathic, drug, food, infection (GAS, viral, parasites)


  • Primary effector cell = mast cell; Ag binds to IgE bound to mast cells leading to degranulation of mediators that cause inflammation


  • IgE bound to high affinity IgE receptors (Fcε receptor I)



    • →Pre-formed mediators = histamine, heparin, tryptase, chymase


    • →Newly formed mediators = prostaglandins, leukotrienes, PAF (platelet activating factor)


  • Stem cell factor, complement C5a anaphylaxatoxin, and substance P can cause degranulation by binding to receptors independent of FcεRI


1.

Physical Urticaria

(a)

Dermatographism

 

(b)

Pressure urticaria

 

(c)

Cold urticaria

 

(d)

Cholinergic urticaria



  • Caused by sweat-inducing stimuli (including heat)

 

(e)

Solar urticaria



  • Acute (lasts only hours) compared to PMLE (lasts for days), exact photoallergen not identified

 

(f)

Contact urticaria



  • Most common plant cause = stinging nettles (Urtica family), contain histamine/serotonin/acetylcholine within sharp hairs


  • Includes aquagenic urticaria (from water contact), not histamine mediated


  • Allergic contact urticaria can be caused by celery, latex


  • See also Eczematous: Contact Dermatitis

 

 

2.

Angioedema



  • Look for stridor, GI/respiratory symptoms


  • Notably can be caused by ACE inhibitors


(a)

C1 esterase inhibitor deficiency (inherited)



  • Never causes urticaria


  • Screen for with C4 level (will be low; in absence of inhibitor of esterase, cannot prevent C4 from being degraded)


  • Treat with danazol

 

(b)

Acquired angioedema (acquired C1EI deficiency)



  • Acquired from association with lymphoproliferative disorders (lymphomas, monoclonal gammopathy) (type I), or from antibodies against C1EI or immune complex consumption (type II)


  • See decreased C4 and C1q (from antibodies or immune complex-medicated consumption)

 

 

3.

Anaphylaxis

 

4.

Non-immunologic urticaria (anaphylactoid drug reaction)



  • Caused by direct mast cell granulation


  • Mnemonic PROMS = polymyxin B, radiocontrast, opioids, muscle relaxants, salicylates/NSAIDS


  • See also Lists: Other Lists: Drug Eruption Mnemonics

 

5.

Urticarial vasculitis



  • Clinically indistinguishable from urticaria, but lasts >24 h


  • Consider vasculitis work-up as well as CH50, C3, C4, C1q, antibodies to C1q


  • See also Vascular: Purpura: Palpable Purpura/Vasculitis


(a)

Hypocomplementemic urticarial vasculitis syndrome



  • Defined by low serum complement levels plus presence of anti-C1q precipitin (in 100 %), decrease in C1 activity

 

(b)

Schnitzler’s syndrome



  • See also Vascular: Urticaria: Urticarial syndromes

 

 

6.

Urticaria multiforme (acute annular urticaria)



  • A new term some are using to describe presentation of urticaria with eccymotic centers often confused for EM


  • Most commonly seen in infants, associated with viruses, immunizations, antibiotics

 

7.

Urticarial syndromes

(a)

Schnitzler’s syndrome



  • Chronic non-pruritic urticaria, FUO, disabling bone pain, hyperostosis, monoclonal IgM gammopathy (most commonly = IgM-κ), which can progress to neoplasm (Waldenström’s)


  • Can cause urticarial vasculitis

 

(b)

Muckle-Wells syndrome

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Oct 6, 2016 | Posted by in Dermatology | Comments Off on Vascular Diseases

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