Investigation of purpuric rash

INVESTIGATIONS OF PURPURIC RASH

Presented by : Dr. Simrat Jit KaurModerator : Dr. Mohanvir Kaur GMC PATIALAINVESTIGATIONS OF PURPURIC RASH

Disorders of hemostasis of vessels and platelets are grouped as PURPURIC DISORDERS as cutaneous and mucosal bleedings are prominent.

OVERVIEW OF TOPICWhat is PURPURA?How we can investigate such cases?How we classify these ?Do we need the battery of tests?Whether detailed history carries importance?What protocol is followed?

DEFINITIONPurpura is the term used to describe the skin lesions that develop when red blood cells extravasate from capillaries. Purpura refers to either pinpoint lesions called petechiae or more widespread lesions known as ecchymoses. It can be differentiated from other erythematous lesions by the use of diascopy, which is the application of a glass slide to the border of the lesions. True purpura does not blanch with pressure.

WHERE IS THE CAUSE IN PURPURAS ????? ? VASCULAR INVOLVEMENT(Wrong with integrity of vessels)

? PLATELET INVOLVEMENT

IS IT QUANTITATIVE ?

IS IT QUALITATIVE?)

A.PURPURAS DUE TO VASCULAR CAUSE

ALLERGIC

HEREDITARY

ATROPHIC

MISCELLANEOUSB.PURPURAS DUE TO THROMBOCYTOPENIA

PLATELET PRODUCTION IS DECREASED

PLATELET DESTRUCTION IS INCREASED DUE TO IMMUNE OR NONIMMUNE CAUSE

ABNORMAL POOLING C.PURPURAS DUE TO QUALITATIVE DEFECTS IN PLATELETS1.Bernard-Soulier Syndrome

2.Glanzmann Thrombasthenia

3.Von Willebrands disease

1.Vascular purpuraALLERGIC

1.HENOCH-SCHONLEIN PURPURA (HSP)

2.LEUKOCYTOCLASTIC ANGITIS

HEREDITARY

1.H.H.T

2.EHLERS-DANLOS SYNDROME

3.MARFAN SYNDROME

4.PSEUDOXANTHOMA ELASTICUM

5.OSTEOGENESIS IMPERFECTA ATROPHIC

1.SENILE PURPURA

2.SCURVY MISC

1.AMYLOIDOSIS

2.SIMPLE EASY BRUISING

3.FAT EMBOLISM

4.PARAPROTEINEMIAS

2.Thrombocytopenic PurpurasA.DECREASED PLATELET PRODUCTION

1.HYPOPLASIA OF MEGKAKARYOCYTES

2.INEFFECTIVE MEGKARYOPOIESIS

3.HEREDITARY THROMBOCYTOPENIA

4.DISORDER OF THROMBOPOIETIC CONTROL

B. INCREASED PLATELET DESTRUCTION

1. IMMUNE DESTRUCTION (AUTOIMMUNE, ALLOIMMUNE)

2. NON-IMMUNE DESTRUCTIONC. ABNORMAL PLATELET DISTRIBUTION OR POOLING

1.DISORDERS OF SPLEEN LIKE INFECTIONS, CONGESTIVE, INFILTERATIVE

2.HYPOTHERMIA

3.DILUTION OF PLATELET WITH MASSIVE TRANSFUSIONS.

Immune thrombocytopenia( autoimmune)IDIOPATHIC-ACUTE AND CHRONIC ITP

ONLY LABELLED AFTER EXCLUDING ALL THE SECONDARY CAUSESSECONDARY CAUSES ARE THERE

DRUGS(LONG LIST)INFECTIONSCOLLAGEN VASCULAR DISORDERSPREGNANCYLPDS

Immune thrombocytopenia( alloimmune)NEONATAL THROMBOCYTOPENIA

2.POST TRANSFUSION PURPURAS

Non-immune thrombocytopeniaTHROMBOTIC MICROANGIOPATHIES

1.T.T.P

2.HUS

3.DICABNORMAL VASCULAR SURFACES CAUSINGPLATELETDAMAGE MASSIVE BLOODTRANSFUSIONSMANY INFECTIONS

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Clinical approach to the patient 1.Examination of rashAppearance of lesions (size, shape, color)Palpable or non palpable Location and pattern of involvement.Associated features ( fever, ulcer, scars).Look for lesions in mucous membranes.Presence of tenderness (suggest inflammatory process).

HESS CAPILLARY RESISTANCE TEST ( TORNIQUET TEST )Pressure in it between diastolic and systolic for 5 minutes.After deflation, the number of petechiae appearing in the next 5 minutes in 3 cm area over the cubital fossa are counted.Presence of more than 20 petechiae is considered a positive test.The test is positive in 1. Increased capillary fragility 2. Thrombocytopenia.

2. DETAILED HISTORY Age : HSP in children, Senile purpura in Elderly. Sex Duration of lesion : ?Acute ?chronic. Associated symptoms : like pain, arthralgia, features of collagen vascular disordersPast history of similar episodeH/o Drug(with list of drugs in your hand), chemotherapy, radiotherapy Family historyIs it a spontaneous bruise or after trivial trauma ? Excessive bleeding after trauma

Expensive and unnecessary additional laboratory studies can be avoided if importance is given to historyLike h/o Drugs taken provide a clue ?? Is it reducing PLT count ???Is it causing PLT function defect e.g. Simply aspirin ingestion

3.SYSTEMIC EXAMINATIONLOOK FOR PALLOR, ANY ORGANOMEGALY OR LYMPHADENOPATHY ?? LEUKAEMIAS OR ???LPDS

ANY SIGNS OF CONNECTIVE TISSUE DISORDERS

NEUROLOGICAL SIGNS(?TTP )SYSTEM RELATED FEATURES

LIST OF INVESTIGATIONS 1. Do we need to go for all the tests at first level??? 2. What is the protocol followed?

List of INVESTIGATIONS

CBC (??IS ANY ASSOCIATED HAEMATOLOGICAL MALIGNANCY)PLATELET COUNT, TO BE CONFIRMED BY PBF ALSOMEAN PLATELET VOLUME, PLATELET DISTRIBUTION WIDTHPBF(?ANY CLUE FOR UNDERLYING CAUSE ?LEUKAEMIAS?RED CELL FRAGMENTATION)HHH

4.INVESTIGATIONS cont.BONE MARROW STUDYIN SUSPECTED CASES OF DIC ALONG WITH PLATELET COUNT, OR WHEN ALONG WITH PURPURAS THERE IS H/O SPONTANEOUS BLEED (PT, APTT, TT)AUTOANTIBODIES SCREENPLATELET SURVIVAL STUDY, TPO LEVELSPLATELET FUNCTION TESTS

To start with we need Platelet countManualAnalyserConfirmation from PBFPC 50,000/cmm

Bleeding time ????Dukes method Ivys method Template method

SCREENING TESTS USUALLY SHOW NORMAL RESULTS IN PURPURAS RELATED TO VASCULAR ABNORMALITIES

Vascular purpuras.ALLERGIC

1.HENOCH-SCHONLEIN PURPURA (HSP)

2.LEUKOCYTOCLASTIC ANGITIS

HEREDITARY

1.H.H.T

2.EHLERS-DANLOS SYNDROME

3.MARFAN SYNDROME

4.PSEUDOXANTHOMA ELASTICUM

5.OSTEOGENESIS IMPERFECTA ATROPHIC

1.SENILE PURPURA

2.SCURVY MISC

1.AMYLOIDOSIS

2.SIMPLE EASY BRUISING

3.FAT EMBOLISM

4.PARAPROTEINEMIAS

HOW TO INVESTIGATE SUCH CASE WHERE VASCULAR CAUSE IS PRESUMED?

CASE NO. 1

CASE -16 yr old child presented with acute colicky abdominal pain, arthritis and lower extremity palpable purpura. There was h/o sore throat, 3 weeks before.Requisition for routine investigation was doneCBC- Leucocytosis with eosinophillia PC NormalUrine examination revealed mild proteinuria, RBCs and pus cells*.

Typical clinical history and investigations were suggestive of HENOCH-SCHONLEIN PURPURA

CONFIRMATION BYIMMUNOCOMPLEXES OF IgG AND IgA - MAY BE INCREASEDBIOPSY SHOWING GRANULOCYTES IN THE WALLS OF ARTERIOLES OR VENULES

What is HENOCH-SCHONLEIN PURPURA !Incidence : 20 per lakhAcute vasculitic syndromeChildren (4-11 yrs)Preceded by -hemolytic streptococcal sore throat, 1-3 weeks before Deposition of circulating immune complexes within the vessels.

CASE- 2A 22 year old male presented with complaint of epistaxis* . On examination telangiectasia on tongue and upper lip were appreciated.h/o similar complaints in elder brother*Investigations: CBC, PC : Normal

Typical clinical presentation and family history was suggestive of Hereditary Hemorrhagic Telangiectasia

CONFIRMATION BY BIOPSYFOLLOW THE CRITERIA FOR DIAGNOSISBiopsy : Post capillary venule dilatation, perivascular infiltrate Mutations in endoglin gene or in the activin receptorlike kinase gene (ALK1) which result in vascular malformations.

SENILE PURPURA FEATURESOld age??Thin skin, atrophy of collagen and loss of fat result in loss of support to small vessels.

INVESTIGATIONSCBC , PC , BT : Normal

SCURVY

INVESTIGATIONS : normalVitamin C promote peptidyl hydroxylation of procollagen. Deficiency causes weakened collagen strands predisposing to capillary fragility and delayed wound healing. History helps

PERIFOLLICULAR HEMORRHAGES IN SCURVY

CASE- 3A 58 yr old female presented with bilateral periorbital purpura. The lesions appeared spontaneously without any trauma. No h/o any drug intake. 3 yr earlier she was diagnosed with multiple myelomaThrombocytopenia

Clinical presentation and history was suggestive of AMYLOIDOSISIn this case biopsy was planned for demonstration of amyloidBiopsy showed amyloid deposits in the dermis and subcutaneous tissues, and scarce inflammatory cells.

light chain deposits in the cutaneous blood vessels. Fragile vessels resulting in purpura on minor trauma (pinch purpura)

Purpura Associated with Skin DiseasesPIGMENTED PURPURIC DERMATITIS

INVESTIGATIONBiopsy : mononuclear upper dermal infiltrate without evidence of leukocytoclasis, extravasated RBCs around capillaries & hemosiderin deposits are seen.

2.Thrombocytopenic PurpurasDECREASED PLATELET PRODUCTION

1.HYPOPLASIA OF MEGKAKARYOCYTES

2.INEFFECTIVE MEGKARYOPOIESIS

3.HEREDITARY THROMBOCYTOPENIA

4.DISORDER OF THROMBOPOIETIC CONTROL

B. INCREASED PLATELET DESTRUCTION

1.IMMUNE DESTRUCTION (AUTOIMMUNE, ALLOIMMUNE)

2. NONIMMUNE DESTRUCTIONC. ABNORMAL PLATELET DISTRIBUTION OR POOLING

1.DISORDERS OF SPLEEN LIKE INFECTIONS, CONGESTIVE, INFILTERATIVE

2.HYPOTHERMIA

3.DILUTION OF PLATELET WITH MASSIVE TRANSFUSIONS.

CASE STUDY WHEN PUPURAS ARE DUE TO INVOLVEMENT OF PLATELETS.

SCREENING TESTS WILL BE ABNORMAL IN QUANTITATIVE DEFECTS

CASE- 426 yr old female presented with repeated episodes of epistaxis, bleeding from gums, ecchymoses and petechiae around the ankles from last 6 months.On detailed history & examination there was no h/o drug intake, no similar family history, no collagen disorder, no organomegaly Investigations CBC : Hb decreased TLC , DLC : normalPC decreasedMPV highPlatelet distribution width increased Reticulocytosis PBFNormocytic normochromic anaemiaPlatelets were abnormally large and there was more variation in size and shape.

PBF Showing thrombocytopenia and large platelet

Bone marrow was planned for labeling whether it was amegakaryocytic thrombocytopenia or megakaryocytic thrombocytopenia and to study the morphology.

Diagnosis of ITP was made after excluding all other causes of thrombocytopenia Demonstration of antiplatelet antibodies (specificity - 78 to 93% , sensitivity 49 to 66%)

What is ITP? Incidence 1.6/10,000 ACUTE ITP Thrombocytopenia occurring for 6 months Require therapy to improve the thrombocytopenia.Adults. F:M=2 to 3:1

PATHOPHYSIOLOGY

THROMBOCYTOPENIC PURPURA SECONDARY TO DRUGS

NOTING ON DRUG INTAKE WILL HELP

Drug induced purpuras

Rifampicin(6 per 100 cases), Quinidine, quinine, Heparin (3 per 100), acetaminophen, trimethoprim-sulfamethoxazole, danazol, methyldopa, digoxin, gold(1 per 100), procainamide, carbamazepine, hydrochlorothiazide, ranitidine, chlorpropamide etc

SLE FEATURESSpecific platelet autoantibodies or immune complexes get deposited on platelets.Malar rash INVESTIGATIONCBC: anaemia, lymphopenia, leukopeniaPC : decreasedBT : prolongedPositive antinuclear antibodyPlatelet autoantibodies

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Cutaneous Leukocytoclastic Vasculitis

SKIN LESIONS HHH Confirmation by Skin biopsy: Fibrinoid necrosis, leukocytoclasis, inflammatory infiltrate ANTIBODIES

CASE- 5A 35 yr old male presented with fever, headache, joint pains, and rash over back in the month of Oct-Nov for 1 week.Investigations :-positive tourniquet test, decreased platelet count, leukopenia, lymphocytosis??? Could be viral etiologyNS1 Ag & Dengue serology was planned which came out to be positive

Suggestive historyThrombocytopenia, LeucopeniaNS1 Ag/Ig MNo other tests needed

Diagnosis of DENGUE HEMORRHAGIC FEVER was made.

PURPURA IN INFECTIONS FEATURESBACTERIAL AND VIRAL CAUSEMECHANISM : DIC, vasculitis, septic emboli, vascular toxins (??direct vascular or endothelial invasion).

INVESTIGATIONSCBC : TLC- increasedPC : Normal or decreasedBT : prolongedSEROLOGIC STUDIES : RISE IN ANTIBODY TITERS Biopsy of the skin lesions with immunofluorescent identification of the organisms.

NEONATAL THROMBOCYTOPENIA FEATURESIncidence : 1 in 1000Result from the placental transfer of platelet antibodies formed as the result of active immunization of the mother by fetal platelet antigens. INVESTIGATIONPC : decreased????? Platelet antigen incompatibility between the parentsPresence of maternal antipaternal platelet antibodies

Non-immune thrombocytopeniaTHROMBOTIC MICROANGIOPATHIES

1.T.T.P

2.HUS

3.DICABNORMAL VASCULAR SURFACES CAUSINGPLATELETDAMAGE MASSIVE BLOODTRANSFUSIONSMANY INFECTIONS

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CASE- 6A 38 yr old female presented with purpuras, fever and seizuresInvestigations -CBC : anaemia, neutrophillia, thrombocytopenia, increased reticulocyte countPBF : polychromasia, nucleated red cells, schistocytes .

RFT Blood urea and serum creatinine were elevatedLDH, unconjugated bilirubin were increasedHaptoglobin levels were reducedHemoglobinuria and Hemosiderinuria was present.

D/DTHROMBOTIC THROMBOCYTOPENIC PURPURAHAEMOLYTIC UREMIC SYNDROME

Age group of the patient and no h/o haemorrhagic diarrhea ruled out the possibility of Haemolytic uraemic syndrome

THROMBOTIC THROMOCYTOPENIC PURPURAIncidence : 2 to 7 per millionHereditary : Mutations of ADAMTS13 gene Acquired : abnormal inhibitors

TTP.BONE MARROW : infrequently performed, but may reveal erythroid hyperplasia, increased numbers of megakaryocytes, and occasionally microvascular hyaline thrombi.ADAMTS13 activity levels are