Review: Pigmented purpura and cutaneous vascular occlusion syndromes *

Abstract

Purpura is defined as a visible hemorrhage in the skin or mucosa, which is not evanescent upon pressure. Proper classification allows a better patient approach due to its multiple diagnoses. Purpuras can be categorized by size, morphology, and other characteristics. The course varies according to the etiology, as do the diagnostic approach and treatment. This review discusses pigmented purpuras and some cutaneous vascular occlusion syndromes.

Full text

An Bras Dermatol. 2018;93(3):397-404.
397
review
Pigmented purpura and cutaneous vascular occlusion syndromes*
AnaCeciliaLamadrid-Zertuche1 VerónicaGarza-Rodríguez1
Jorge de Jesús Ocampo-Candiani1
s
Received04August2017.
Accepted03November2017.
* WorkconductedattheDermatologyDepartment,UniversityHospital“Dr.JoséEleuterioGonzález”,UniversidadAutónomadeNuevoLeón,NuevoLeón,
México.
Financial support: None.
 Conictofinterest:None.
1 DermatologyDepartment,UniversityHospital“Dr.JoséEleuterioGonzález”,UniversidadAutónomadeNuevoLeón,NuevoLeón,México.
Mailing address:
VerónicaGarza-Rodríguez
Email:verogarzardz@gmail.com
©2018byAnaisBrasileirosdeDermatologia
INTRODUCTION
Purpuraisdenedasavisiblehemorrhageintheskinor
mucosathatisnotevanescentuponpressure.Properclassication
provides a better patient approach due to the multiple diagnoses of
purpura.Purpurascanbeclassiedbysize,morphology,pathophy-
siology,andothercharacteristics(Table1).
Regardingmorphology,retiform purpura should be diffe-
rentiated from livedo reticularis and livedo racemosa. These conditions
have a similar morphological appearance, characterized as viola-
ceousmaculesinanet-like,arborized,orstarryformbuttheydiffer
inpathophysiology(Chart1).
The clinical course varies according to the etiology. Macular
purpura or non-palpable purpura heals faster and exhibits a col-
ortransitionfrom red-bluetoviolaceous,green,yellow,or brown
duetoextravasationoferythrocytesandfew inammatory cells.1
Palpablepurpuratakeslongertohealduetothepresenceofinam-
matory cells and immune complex deposits that lead to vascular
occlusion.1
Purpura has a long list of differential diagnoses, which
differ particularly in their pathophysiology. One way to approach
purpuraisbyansweringthe question, “Is the patient bleeding?”,
sincesomebleedingdisordersrequireurgenttreatment(Figure1).
The purpose of this review is to describe some of the differential
diagnoses and their physiopathogenic mechanisms to provide a bet-
DOI: http://dx.doi.org/10.1590/abd1806-4841.20187459
Abstract: Purpuraisdenedasavisiblehemorrhageintheskinormucosa,whichisnotevanescentuponpressure.Proper
classicationallowsabetterpatientapproachduetoitsmultiplediagnoses.Purpurascanbecategorizedbysize,morphology,
andothercharacteristics.Thecoursevariesaccordingtotheetiology,asdothediagnosticapproachandtreatment.Thisreview
discusses pigmented purpuras and some cutaneous vascular occlusion syndromes.
Keywords: Antiphospholipidsyndrome;Calciphylaxis;Myeloproliferativedisorders;Purpura;Purpurafulminans;Vascular
diseases
table 1: Purpura classication
Size Morphology Characteristics
≤4mm=petechiae Retiform Inammatory
5 to 9mm = macule Non-retiform Non-inammatory
≥1cm=ecchymosis Livedo reticularis
Livedo racemosa
Source:PietteWW,2012.1
Source:WysongA,et al, 2011.16
chart 1: Livedo reticularis, livedo racemosa, and retiform purpu-
ra characteristics
Pathophysiology Topography
Livedo reticularis Lowbloodowdue
to low output state.
Lower extremities
Livedo racemosa Irregularbloodow
due to mechanical
obstruction.
Trunkandlower
extremities
Retiform purpura Purpura and necro-
sis due to venous
occlusion.
Variable

Figure 1: Purpura: diagnostic algorithm
An Bras Dermatol. 2018;93(3):397-404.
ter patient approach and guide treatment. This article will discuss
pigmented purpuras and some cutaneous vascular occlusion syn-
dromes. Although vasculitis is part of the differential diagnoses, it
will not be discussed in this review.
Pigmented purpuras
Pigmented purpuras, also known as chronic pigmented
purpuric dermatosis, purpura simplex, and capillaritis, among oth-
ers, encompasses ve major clinical variants, including Schamberg’s
purpura, purpura annularis telangiectodes of Majocchi, pigment-
ed purpuric lichenoid dermatitis of Gougerot and Blum, eczema-
tid-like purpura of Doucas and Kapetanakis, and lichen aureus.1-4
Each condition is associated with different triggers, which are dif-
cult to establish in practice and do not appear to have therapeutic or
prognostic implications.3,4
Capillaritis is associated with many triggers, including ve-
nous hypertension, exercise, pregnancy, frail capillaries, drug tox-
icity from acetaminophen, aspirin, hydralazine, and thiamine, and
hyperactive substances such as textiles, colorants, and alcohol.2,3 Id-
iopathic capillaritis is the most common form, since most cases are
not associated with a specic trigger.4
Epidemiological data are lacking. However, a 5-fold in-
creased prevalence is noted in men compared to women. The con-
dition predominantly affects adults 40 to 60 years of age.2,5 Some
variants predominate in children and young adults.3-5
The physiopathogenesis is unknown, but the condition is
believed to be due to a cutaneous hypersensitivity reaction that
causes capillary fragility and permeability, leading to erythrocyte
extravasation and hemosiderin deposits noted on biopsy.1,2,6 The
following three main pathogenic theories have been described ac-
cording to histological data: vascular fragility, humoral immunity,
and cellular immunity.2,3
Pigmented purpuras present as petechiae or pigmented ma-
cules on distal lower extremities.1-4 These lesions can be generalized,
due to self-limiting viral infection, or localized. All variants have
specic distinguishing clinical characteristics (Chart 2).
398 Lamadrid-Zertuche AC, Garza-Rodríguez V, Ocampo-Candiani JJ
NPH: nocturnal paroxysmal hemoglobinuria; TTP: thrombotic thrombocytopenic purpura; APS: antiphospholipid syndrome; HIT: heparin-induced thrombocytopenia; ITP: ldiopathic
thrombocytopenic purpura; NSAID: non-steroidal anti-inammatory drugs; DIC: disseminated intravascular coagulation
Purpura
Is the patient
bleeding?
Yes
Thrombocytosis
Myeloproliferative
disorder
NPH
TTP (rare)
Dilution
Von willebrand`s
disease Infection Myeloproliferative
disorders
Ehrles-Danlos
Crioaglutination
Infective organisms
(immunosupressed
patients, pyoderma
gangrenosum,
Lucios, Leprosy,
etc.)
Connective tissue
disease (APS) Drugs
Gardner-Diamond
syndrome
(psychogenic)
Valsalva
maneuver
Purpura
fulminans (sepsis)
TTP
HIT
ITP
Abrinogenemia Renal failure
Vitamin K
deciency
DIC Marantic
endocarditis
Procoagulant
dilution Mondor disease
Drugs
Factor v and
protein C
deciency Hepatic failure
Drugs (aspirin,
clopidogrel, ab-
ciximab, NSAID,
antibiotics,
bronolitics, etc.
Calcyphylaxis Scurvy
Amyloidosis Trauma
Child abuse
APS
Catheter
Hemophilia A, B warfarin necrosis
Thrombocytopenia
Emergency Other Congenital Acquired Small, medium
and larg vessel Senile purpura
Increased
intravascular
pressure
Embolism
(cholesterol,
crystal, fat, infective,
myxoma)
Coagulation
disorder
Pigmented
purpura Vasculitis Vessel wall
support problem Asprted entities
No
Vascular occlusive
syndromes
Spider bite
(Loxoceles)

An Bras Dermatol. 2018;93(3):397-404.
Source:DíazMolinaVLet al.,20092; Sardana K et al.,20043;AllevatoMA,20074;KaradagASet al.,20135,andHoeslyFJet al,,2009. 7
chart 2: Pigmented purpuras
Clinical appearance Topography Histology
Schamberg’sPurpura Purpuricmaculesforminglargeplaques
thatacquireabrownishcolordescribed
as“Cayennepeppergrains”
Lower limbs
(pretibial)
Perivascularlymphocyticinltrate,
with erythrocyte extravasation and
hemosiderin deposit
Eczematid-likepurpuraof
DoucasandKatepanakis
Eczematouschangeswithlichenication Lower limbs
Purpura annularis telangiec-
todesofMajocchi
Symmetricannularbrown-redmacules,
with a clear atrophic center
Lower limbs
GeugerotandBlum’sDisease licheniedorange-redorpurpuric
plaques
Legs,thighs,
trunk,andocca-
sionally arms
Lichen aureus Purpuric macules with orange or golden
lichenoid papules
Lower limbs Same characteristics as lichenoid
band-likedermallymphocyte
inltrate
Linear capillaritis Similar to lichen aureus with linear
pattern
Lower limbs Same as other pigmented purpuras
Schamberg’s purpura
Thisconditionisalsoknownasprogressiveorchronicpur-
puric dermatosis. Schamberg’s purpura predominates in men in
their 50s and is associated with viral infections. 2 The condition typ-
icallyinvolvesthepretibialregionandextendsproximally,sparing
the face, palmo-plantar regions. 3 Schamberg’s purpura typically
presentsaspurpuricmaculesforminglargeplaquesthat acquirea
brownishcolordescribedas“Cayennepeppergrains”.2,3 The lesions
tend to be asymptomatic but are sometimes mildly pruritic.3
Eczematid-like Purpura of Doucas and Katepanakis
Eczematid-likepurpura oritchingpurpura isdescribedas
avariantofSchamberg’spurpura3,5 that typically affects men.5 The
conditionischaracterizedbyeczematous alterations on the lower
extremitiesassociatedwithpruritusandsecondarylichenication
in patients who scratch the purpura.4,5 Similar to other types of cap-
illaritis,theconditionhasachroniccoursewithspontaneousremis-
sion.3,5 This purpura has been associated with an allergic reaction
to textiles.3,4
Purpura annularis telangiectodes of Majocchi
Thisconditionischaracterizedbysymmetriclesions,pre-
dominantly affecting the lower extremities with proximal extension
tothebuttocks.3 The lesions appear as brownish-red purpuric mac-
ules with an annular or arciform pattern2 and clear center3 that can
become atrophic.7Thelesionscanbeconfusedwithvasculitis,soit
isimportant to takethisintoaccount.4 Theetiology isunclear,but
theconditionisassociatedwithpregnancyandvenousinsufciency
that worsens with textile friction.2,4 It mainly affects adolescent girls
and young adult women.4,7 The lesions typically display a chronic
asymptomaticcourse,butcanbeassociatedwithpruritus.2,4
Gougerot and Blum’s disease
Lichenoid purpuric dermatosis or Gougerot and Blum’s
disease affects adults between 40 and 60 years of age.2 The condition
ischaracterizedbylicheniedplaqueswithanorangish-redorpur-
plish color on the anterior regions of lower extremities (lower legs
andthighs),trunk,andoccasionallyarms.2,4,8Whensingle,alesion
canmimicKaposi’ssarcoma.2,4 Some cases may be associated with
mycosis fungoides.2,4
Lichen aureus
Alsocalledpurpuric lichen, lichen aureusisnamedfor to
its golden color.3Affectingyoung adults between 20and30years
ofage,it is characterized by typically unilateralorangeorgolden
purpuric macules with lichenoid papules on the lower extremi-
ties.2-4Thelesionsareoftenchronic,lastingbetween3monthsand
20 years.4Theconditionmaybeassociatedwithdrugs,trauma, or
venous stasis.4Itshareshistologicalcharacteristics,suchaseryth-
rocyteextravasationandperivascularinltrate,withothertypesof
capillaritis but characteristically presents a band-like lymphocyte
inltratebelow aneGrenz zone4 that distinguishes it from other
types of capillaritis on histopathology.
Linear capillaritis
Linearcapillaritis,orpigmentedpurpuricdermatosis,looks
similartolichenaureuswithalineardistribution.However,histo-
logically, the condition does not present with lichenoid inltrate.2
Theconditionisvetimesmorecommoninmenthanwomenand
appears on the lower extremities.9
Diagnosis, treatment, and prognosis
Diagnosis is clinical. Pigmented purpuras typically exhib-
itanasymptomaticcoursewithminimalpruritus,occasionalpain,
and normal laboratory ndings.2 Some cases require a biopsy to
distinguishthemfromotherentities,suchasvasculitis.On histo-
pathology,pigmentedpurpurasexhibitaperivascularlymphocytic
inltrate,vasculardilationwitherythrocyteextravasation,andhe-
Pigmented purpura and cutaneous vascular occlusion syndromes 399

400 Lamadrid-Zertuche AC, Garza-Rodríguez V, Ocampo-Candiani JJ
specicity.13,17 Conrmation with anti-PF2/heparin antibodies by
enzymeimmunoassay(EIA)isalsorecommended.13
Treatment is based on discontinuing heparin and using an
alternative anticoagulant therapy such as a thrombin inhibitor fol-
lowedbyvitaminK,ifneeded.12,15,16Alternativeheparinisreserved
for cases not associated with HIT syndrome.12 Wound care, pain
management,and surgical debridement and skingraft should be
provided when needed.12,16
Thrombocytopenia secondary to myeloproliferative dis-
orders
Myeloproliferative disorders are characterized by abnor-
mal proliferation of one or more cell lines on peripheral blood tests.
Theconditiondiffersfromacuteleukemiaandmainlyaffectsyoung
women.11 Polycythemia vera and essential thrombocytopenia are the
mostcommonformsaffectingtheskin.11 These conditions can present
ascutaneous vascularocclusionsyndromesintheformofpurpura,
hematomas,erythromelalgia,livedo reticularis, Raynaud’s phenome-
non,legulcers,gangrene,andthrombophlebitis.11,18,19 The molecular
pathogenesisimplicatedinthesediseasesispoorlyknown, butmu-
tationsintheJAK-2proteinkinasegenehavebeendescribedin90to
95%ofpatientswithpolycythemiaveraandin50to70%ofpatients
with essential thrombocytopenia.11 Platelet thrombi can be found in
thedermalbloodvesselsofskinbiopsies.20 Patients with this sign ex-
hibit increased morbidity due to greater thrombotic or hemorrhagic
potentialor transformationtomyelobrosisorleukemia,compared
to the general population.21 Treatment is oriented by age and cardio-
vascularrisk.Anagrelide,low-doseaspirin,hydroxyurea,andphle-
botomy have been useful in cases of polycythemia vera.21
Purpura due to cryoagglutination or cryogelling disorders
Cryoagglutination disorders include cryoglobulinemias,
cryobrinogenemias,andcoldagglutinins.11 These syndromes are
uncommon but should be taken into account for the differential
diagnosis of vascular occlusion syndromes. Immunoglobulin pre-
cipitatesat temperatures below 4°Cand dissolves at 37°C, corre-
sponding to cryoglobulinemias.22,23Cryobrinogenemiasarecaused
byplasmabrinogensthatgelatlowtemperatures,andcoldagglu-
tinin antibodies promote erythrocyte agglutination at cold tempera-
tures,causingvascularocclusion.11
Cryoglobulinemiascan be categorized into 3 types accor-
dingto Brouet’s classication (Chart 3).22,23 Type 1 is vascular oc-
clusive,whereastypes2and3causesmallvesselvasculitisdueto
immunecomplexes.Theseconditionsaffectwomenmorefrequently
(ataratioof3:1),andtheleastcommoncryoglobulinemiaistype1.23
Theetiologyisbased onautoimmunediseasesin10to15% ofmi-
xedcryoglobulinemia,hematologicneoplasmsin10to15%oftype
1cryoglobulinemia,andidiopathicorinfectiousin25%ofcasesof
mixed cryoglobulinemia.22 The pathogenic mechanism is based on
monoclonal or polyclonal antibodies secondary to lymphoprolife-
rative or immune stimulation due to infectious or autoimmune di-
seases.23,24Thissectionfocusesontype1cryoglobulinemia,sincethe
other two types cause vasculitis due to immune complexes.
Type1cryoglobulinemiasaffectskinandothersystemsac-
cording to their pathophysiological mechanism of hyperviscosity
mosiderin deposits.
Nostandardtherapyisavailable,buttreatmentshouldfo-
cusonavoidingtriggers.Sometreatments,suchastopicalsteroids,
griseofulvin, pentoxifylline, vitamin C, and phototherapy have
reportedsuccess, with responsevaryingbetweenpatients.5,9,10 Ste-
roid-sparing drugs such as cyclosporine and other immunomodu-
lators such as methotrexate have been used with good results.7 Pa-
tientscanbemanagedconservativelywithcompressivestockings
and lower-extremity lifting to help venous stasis.2,7,9
Pigmentedpurpurashaveachronicbenigncourse.However,
some cases have been associated with T-cell lymphoma.2,3,4,7 These le-
sionsleaveapostinammatorymaculethatisdifculttotreat.2
Cutaneous manifestations of microvascular occlusion
syndromes
Cutaneous manifestations of microvascular occlusion syn-
dromesarecharacterizedbyretiformpurpura.Inammatory and
non-inammatoryretiform purpurashouldbedistinguished from
eachother,andpertinentbloodtestsshouldbe performedaccord-
inglytonarrowthe diagnosis and provideappropriatetreatment,
giventhenumerousdifferentialdiagnoses.In addition, treatment
varies according to the etiology. The condition is harmful if incor-
rectlytreatedasanocclusiveorinammatorysyndrome.11
The differential diagnoses are numerous. This section in-
cludessomeofthem,buttheclinicianshouldtakeallotheroptions
into account. Pathophysiology is a simple method for classifying the
conditions and orienting diagnosis.11
Disorders based on platelet aggregation
Heparin-induced necrosis
Heparin necrosis is a clinical and pathological entity that re-
quirespreviousheparinexposure.11-13 The patient presents retiform
non-inammatorynecrotizingpurpuratypicallyveto11daysafter
exposure,butimmediatelyif therehasbeenpreviousexposureora
late hypersensitive reaction months later.11,12 Lesions typically begin
aspainfulerythematousplaquesthatprogresstopurpurawithrapid
necrosis at the site or distal from heparin application with a predilec-
tionfortheabdomen, thighs,andlegs.11,12Aplateletplugwith peri-
vascularinammationcanbeobservedonhistopathology.14
The condition affects 1 to 5% of adults, especially mid-
dle-aged women with a 30% incidence and mortality.11,12,15 The
followingpathophysiological mechanisms havebeenproposed:1)
heparin-induced immunity in which IgG antibodies are directed
againstplateletfactor4andheparin,causingplateletpluggingand
consumption leading to microvascular occlusion;11-132)Arthus-type
IIIhypersensitivityreaction;and3)physicalandmechanicalfactors,
suchaspoorinjectiontechniqueorpooradiposetissuecirculation.12
It is mandatory to rule out heparin-induced thrombocyto-
penia or HIT syndrome to guide treatment.16 HIT characteristical-
lypresents with thrombocytopenia (30-50% ofbaseline value) af-
ter heparin exposure.13Ten to 20% of patients exhibit anelevated
INR value and hypobrinogenemia consistent with disseminated
intravascularcoagulation(DIC)andpositiveserologicaltests,such
asplatelet serotonin-releaseassay (SRA), which is considered the
“goldstandard” forHITdiagnosiswith88% sensitivity and100%
An Bras Dermatol. 2018;93(3):397-404.

Pigmented purpura and cutaneous vascular occlusion syndromes 401
An Bras Dermatol. 2018;93(3):397-404.
FIgure 2: Ecthyma gangrenosum-like due to aspergillosis in a 6-year-
old immunosuppressed patient
or vascular occlusion due to protein precipitation. These conditions
affectskinaspurpurainacralareasexposedtocoldtemperatures,
acrocyanosis,necrosis, cutaneous ulcers, Raynaud’s phenomenon,
and livedo reticularis.11,22,23Othersystemsareaffected,andsymptoms
includeheadache,confusion,blurredvision,epistaxis,andhearing
loss.22Skinulcersandnecrosisaremorecommonintype1cryoglob-
ulinemia than in types 2 or 3.25 Diagnosis is made by clinical suspi-
cion,presenceofserumcryoglobulins onimmunoelectrophoresis,
immunoxation,orimmunoblottingwith98,54and28%sensitivity
andspecicity,respectively,andskinbiopsyexhibitingnon-inam-
matory thrombosis.23,25
Prognosisispoor due to skin severityand the associated
hematological disorders.22 Reported survival rates vary from 87 to
94%.26 Treatment should be individualized for patients based on
their comorbidities, pathological mechanism, and disease severi-
ty.22,23 The most important measure is to avoid exposure to cold. Cor-
ticosteroids,cyclophosphamide,orbiologics,andplasmaexchange
forseverehyperviscositycanbeusedinindividualizedcases.22,23,24
Vascular occlusion due to microorganisms
These syndromes cause vascular occlusion due to microor-
ganisms and mainly affect immunosuppressed patients. The group
includesecthymagangrenosum,Lucio’sleprosy,opportunisticfun-
galinfections,andothers.
Ecthyma gangrenosum is characterized by red to purple
macules that form pustules or hemorrhagic ampules that evolve
into necrotic ulcers within 12 to 24 hours (Figure 2).27,28Bacterial
proliferationonsubcutaneousvesseladventitiaformsathrombus,
causingvascularocclusionmainlyinthebuttocksandlowerextre-
mities.11,27,29Absenceofsuppurationdifferentiatesecthymagangre-
nosum from pyoderma gangrenosum.27Intotal, 73.65%ofcasesof
ecthyma gangrenosum are due to Pseudomonas aeruginosa,whereas
17.35%and9%aredue to other bacteria and opportunistic fungi,
respectively.Theformercasesshouldbereferredtoas“ecthyma gan-
grenosum-like”.29Acompromisedimmune system isnotanobliga-
toryfactor forthedisease buthasbeen reportedin59% ofcases.29
Diagnosisismadewithclinicalsuspicionandskincultures.Dermal
necrosis with neutrophil and lymphocyte inammatory inltrate
andvasculitiswithocclusivethrombihavebeendescribedonskin
biopsy.28 Gram-negative bacteria can be found on vascular adventi-
tia and perivascular areas. 11
Lucio’sleprosy,alsoreferredtoasnecrotizingerythemaof
Latapi,isatype 2 reaction that corresponds to a necrotizing vas-
culitis with thrombosis.30 The condition is found mainly in Mexico
andCentralAmerica,affectingpatientswithprimitivelepromatous
leprosy and non-nodular secondary diffuse types.30,31 It has a 5-day
course initiating on the lower extremities and progressing upward
until reaching the face.30,31 The lesions begin as purpuric macules
surrounded by erythema that progress to bullae that necrotize.31
Skinbiopsyndingsdependonthestageofevolutionatwhichthe
biopsyisobtained,butacid-fastbacilliwithFite-Faracoarealways
present.30
The treatment of vascular occlusion syndromes due to mi-
croorganisms aims to improve the patient’s immune status and
treat infection. In ecthyma gangrenosum, antibiotics should be
administered empirically with aggressive treatment against fungi
and bacteria generally with ceftazidime, ampicillin, amoxicillin/
clavulanic acid, or amphotericin B. In addition, surgical debride-
ment is performed when indicated.29 These patients have a poor
prognosiswhenassociatedwithbacteremia,resultingin20to50%
mortality.28 For Lucio’s leprosy, thalidomide (200 to 600mg/day)
should be administered until a response is observed.30Alternatively,
plasmapheresis is provided in non-responsive cases together with
multibacillarytreatmentandhigh-doseprednisone(1mg/kg)with
monthly tapering.31
Purpura due to embolization disorders
Cholesterol embolism
Thisconditioniscalled“bluetoesyndrome”.Thedisorder
affectsmen50 years or older, of whom 15 to20%have a history
ofatheroscleroticdisease,diabetesmellitus,hyperlipidemia,hyper-
*RF(rheumatoidfactor),HIV(humanimmunodeciencyvirus),SLE(systemiclupuserythematosus).Source:Perez-Alamino,Ret al, 201422andGhetieD,et al, 2015. 23
chart 3: Cryoglobulinemia: Classication and Characteristics
Cryoglobulinemias Type I Type II Type III
Antibodytype Monoclonal IgM or IgG Polyclonal IgG and monoclonal
IgM,positiveRF
PolyclonalIgGandIgM,RF
positive
Vascularocclusive
mechanism
Hyperviscosity Immune complex Immune complex
Comorbidities Hematological neoplasm (Type B lym-
phoproliferative disorders: Walden-
strom’smacroglobulinemia,multiple
myeloma,monoclonalgammopathy)
HepatitisCorB,HIV,autoim-
mune diseases
Autoimmunediseases(Sjogren
syndrome,SLE,rheumatoidar-
thritis),hepatitisC,idiopathic.

FIgure 3: a and b- Disseminated ecchymotic purpura in a male
patient with meningoccocemia
An Bras Dermatol. 2018;93(3):397-404.
tension,and/orsmoking.11,32 Cholesterol embolisms are caused by
atheromatousplaquefragmentationsecondarytoaforcethatcauses
plaqueinstability, such as cardiac catheterization, prolongedanti-
coagulation,antithrombotictherapy,hemorrhage,inammation,or
infection.Thelesionspresentinhours,days,ormonths.11,33 In to-
tal,20%ofcasesarespontaneous.32 Manifestations are noted on the
skinin35-88%ofcasesaswellasinthekidneysanddigestivetract,
withavarietyofcutaneouslesions,suchaslivedo reticularisin40%,
peripheral gangrene in 35%, cyanosis in 28%, ulceration in 17%,
nodulesin 10%,andpurpurain9%,alongwith malaise.11,32,34Skin
manifestations are bilateral and limited to the lower extremities,
with normal peripheral pulses.33Skinbiopsiesrevealintravascular
cleftsthatarediagnosticin92%ofcasesandcorrespondtocholes-
terolcrystalsthatdissolvewhilexingthetissue.11,32 The condition
carriesapoorprognosiswithahighmortalityrate(81%),secondary
to cardiac and renal complications.34 Treatment is supportive with
aspirin,statins,prostacyclinanalogs,discontinuationofanticoagu-
lation,and bypassorendarterectomyinspecialcases.11 The use of
systemic steroids is controversial.32,33
Systemic coagulopathies
Warfarin-induced necrosis
This condition is due to abnormal γ-carboxylation of vita-
minK-dependent factors,includingproteinsCand S,leadingto a
hypercoagulable state in 24 to 48 hours.11,35,36 The condition mostly
occursinwomen(4:1ratio)from60to70yearsofage,especiallyin
patientswithcongenitalproteinCdeciency.11,36Ithasa<0.1%inci-
denceintreatedpatients,presentingin90%ofcasesapproximately
2 to 5 days after initiating treatment.35 Manifestations are apparent
inareasofsubcutaneousfat,suchasthechest,abdomen,buttocks,
andthighs,andarecharacterizedbywell-denedpainfulerythema
that turns purplish and necrotic.11 Diagnosis is made by clinical sus-
picionandisdifferentiatedfromhematoma,disseminatedintravas-
cularcoagulation,purpura fulminans,cellulitis,andcalciphylaxis.37
Histopathologyoftheskinshowsnon-inammatorythrombosisof
dermal blood vessels.11 Treatment consists of the discontinuation of
warfarin and administration of vitamin K. Heparin is administered
incaseswhenanticoagulationisneeded,andproteinCconcentrates
are also provided.35-37
Purpura fulminans
Purpura fulminans is a term used to describe any clinical
presentationof disseminated purpura (ecchymosis, palpable, and
retiform)insepticpatients.Neonatal,acute,andidiopathicpresen-
tations have been described.38Clinical lesions reectdisseminated
intravascularcoagulopathyduetodeciencyordysfunctionofcoa-
gulationfactors suchasproteinC,S,orantithrombinIII,manifes-
tingasdistalsymmetricgangrene(Figure3).1135,39 The lesions begin
asnon-blanchable,painful,distalpurpuriclesionswithanindura-
ted halo evolving into bullae that turn hemorrhagic and necrotic.39
This purpura is mainly due to meningococcal infection but can be
secondary to other bacterial or viral infections.11 Blood tests are con-
sistent with disseminated intravascular coagulation.11,38Skinbiopsy
revealsbrinclotsindermalvesselswithsomeinammatoryinl-
trate.35Thecase-fatalityrateishighat50%,andrequiresmultidisci-
plinarytreatmentwithbloodandcoagulationfactortransfusions,
plasmaexchangewithprednisone,andheparinanticoagulation.11,38
Antiphospholipid antibody syndrome
Antiphospholipidantibodysyndrome(APS)causescutane-
ous or systemic vessel occlusion due to anticardiolipin antibodies
and circulating antiphospholipids that damage endothelial cells
upon binding to exposed phospholipids and interfering with nor-
malprocoagulantprotection,leadingtothrombosis.11 The condition
affectsthe skin in70%ofcases,presenting as avarietyofskinle-
sions,including livedo reticularisandgangrene.Ararecatastrophic
variantis noted in 1% of caseswitha 50% mortality rate.11,40 The
condition mainly affects women between 15 and 50 years of age.11
Testing for anticardiolipin antibodies can be ordered upon suspi-
cion,andanti-ß2glycoproteinsaremorespecic.Inaddition,the
lupusanticoagulantandVenerealDiseaseResearchLaboratorytests
(VDRL)showpositiveresults.11,40Histopathologyofskinlesionsre-
vealsnon-inammatory thrombosisofdermal vessels.41 Treatment
isbased on clinical history and patient risk.Anticoagulationand
antiplateletdrugsareadministered inlow-riskpatients, andhigh-
dose systemic steroids with anticoagulation, intravenous gamma
globulin,andplasmaareadministeredinhigh-riskpatients.40,42
Others: Calciphylaxis
Calciphylaxis,alsoknownascalcifyingpanniculitisorcalci-
curemicarteriolopathy,isalethaldiseasethataffectschronicrenal
patientsonhemodialysisandhyperparathyroidismpatients,with
80%case-fatality rate.11, 43-45 Manifestations include calcicationof
thearterialmidlayerandsubintimalbrosisfollowedbythrombotic
occlusion.43Theconditionaffectsareassuchasabdomen,buttocks,
andthighs,withvariedclinicalmanifestationsincludinglivedo reti-
cularis,plaques,orpainfulviolaceoussubcutaneousnoduleswith
necrotic ulcers and eschar with superinfection in some cases (Figure
4).44SkinbiopsyrevealsVonKossa-positivecalciumdepositsinthe
arterialmidlayer,intimalbrosis,andintraluminalthrombusalong
with erythrocyte extravasation.45,46 Treatment should be aggressive
AB
402 Lamadrid-Zertuche AC, Garza-Rodríguez V, Ocampo-Candiani JJ

An Bras Dermatol. 2018;93(3):397-404.
Pigmented purpura and cutaneous vascular occlusion syndromes 403
diumthiosulfate as acalciumbinder,bisphosphonates,cinacalcet,
low-calcium dialysis,hyperbaricoxygen therapy,andparathyroi-
dectomy.11,43,44Steroidsaresparedduetosuperinfectionriskbutcan
be used in early-stage cases without necrosis.43,44 The diagnosis car-
ries a poor prognosis.
CONCLUSION
Purpura is one of the most frequent conditions seen in
dermatology practice and covers a wide range of differential diag-
noses. It is important to consider all differential diagnoses and to
knowtheirbasicpathophysiologybecausetreatmentvariesgreatly
accordingtoetiology,despite the fact that the biopsy and clinical
manifestationsmayseemverysimilar.Vasculitisisalsowithinthe
spectrumofdifferentials.However,thisveryimportantandexten-
sivetopicisnotincludedinthisreview,butweshouldnotforgetto
takethiscondition into accountwhenapproachinga patientwith
purpura. q
FIgure 4: Purpuricplaqueswithnecrosisinpatientwithcalciphy-
laxis
andincludemetabolicmonitoringofcalcium,phosphate,andpara-
thyroidhormonelevels.Treatmentisbasedonphosphatebinders,a
phosphorus-freediet,discontinuationofvitaminD,andantibiotics
in case of superinfection.43 Other treatments include intravenous so-
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An Bras Dermatol. 2018;93(3):397-404.
How to cite this article: Lamadrid-ZertucheAC, Garza-RodríguezV, Ocampo-Candiani JJ.  Pigmentedpurpuraandcutaneous vascular
occlusionsyndromes.AnBrasDermatol.2018;93(3):397-404.
AnaCeciliaLamadrid-Zertuche 0000-0002-4766-8740
VerónicaGarza-Rodríguez 0000-0002-5496-3262
Jorge de Jesús Ocampo-Candiani 0000-0002-0213-0031