Clinical Brief

Correspondence and Reprint requests : Dr A.V. Lalitha,Department of Pediatrics, St John's Medical College Hospital,Bangalore-560034, Karnataka, India[Received August 7, 2006; Accepted July 8, 2008]

Purpura Fulminans (PF) is a catastrophic disease ofchildhood characterized by the sudden appearance ofsymmetrical, tender, ecchymotic skin lesions usuallyinvolving the lower extremities.1 This phenomenon hasalso been described as Purpura hemorrhagica, Purpuranecrotica, Purpura gangrenosa and post-infectiousintravascular thrombosis with gangrene. Many caseshave been reported in the pediatric literature, and about90 percent of them have been fatal.2 With advent of newtherapeutic approaches, the survival rate has increased,but because of the massive gangrene, many survivorsrequire amputation. This report of 5 cases of PF presentsthe clinical features, laboratory findings includingspectrum of manifestation.

CASE REPORT

An eighteen-month old previously healthy female childpresented with fever of 10 days duration, rash since 3rd

day of fever and generalized swelling for a day. Onphysical examination vitals were stable. Pallor andgeneralized edema was present. Dusky reticulate rashover trunk and upper limb, blackish stellate patch overlower limbs and discoloration of toes & fingers werepresent. Systemic examination was found to be normal.

Hemogram revealed anemia with neutrophilicleucocytosis (TC-17000/mm3,90% polymorphs) at

Spectrum of Purpura Fulminans

A.V. Lalitha, D. Aruna, Anand Prakash, H.M. Nanjunda Swamy and S.D. Subba Rao

Department of Pediatrics, St John's Medical College Hospital, Bangalore, Karnataka, India

ABSTRACT

Purpura Fulminans is a severe disorder of acute onset with high morbidity and mortality. It is characterized by DIC withthrombocytopenia, hyofibrinogenemia, hypothrombinemia and anemia. It most often occurs in young with sudden appearanceof symmetrical, tender, ecchymotic skin lesions usually involving the lower extremities. An infectious and noninfectious etiologyhas been proposed. Early recognition and early therapy with appropriate antibiotics and heparin is known to limit both morbidityand mortality. This article reports 5 cases of Purpura Fulminans treated at our centre with review of etiology, pathogenesis,clinical features and treatment. [Indian J Pediatr 2009; 76 (1) : 87-89] E-mail : drlalitha 04@yahoo.com

Key words : Purpura fulminans; Heparin; Protein C

admission. Repeat counts showed increased leucocytosiswith thrombocytopenia. Coagulation parameters werenormal. Blood and Wound culture sensitivity showedCoagulase negative staphylococci sensitive to cloxacillin.

Protein C and S activity was 58% of normal. Skin

Figs. 1, 2. Clinical photograph of a child with Purpura fulminans

Fig. 2

Fig. 1

Indian Journal of Pediatrics, Volume 76—January, 2009 87

A.V. Lalitha et al

88 Indian Journal of Pediatrics, Volume 76—January, 2009

Biopsy showed involvement of dermis with focalperivascular neutrophilic infiltrates. Blood vessels in thedeeper dermis showed fibrin thrombi consistent withPF.Baby were started on Ceftazidime, Amikacin andCloxacillin. In view of worsening of skin lesions, Heparinwas given for 1 week. Fifteen days later the discolorationof digits had demarcated with dry gangrene (Fig 1& 2).Four other children presented with similar skin lesions.

The clinical and laboratory features observed in allchildren are summarized in table 1 & 2. All childrenpresented with fever and maculopapular rash withgangrenous areas involving mainly the extremities. Twochildren had neurological manifestations in the form of

altered sensorium and seizures and three patients neededventilation. Anemia, leucocytosis and thrombocytopeniawere present in all cases. One of the patients hadneuroimaging that was found to be normal. Weil Felixreaction showed raising titers in two children.

DISCUSSION

PF is not a specific diagnosis, but a syndrome. Threedistinct categories can be identified: inherited or acquiredabnormalities of protein C or other coagulation systems,‘acute infectious’ PF and ‘idiopathic’. Inherited andacquired abnormalities of the protein C and Santicoagulant pathway are thought to be responsible for

TABLE 2. Laboratory Investigations

Hb(g/dl) TC (per mm3)/ Platelet PT(s)/INR Blood Others Skin BiopsyDC (per mm3) Culture Investigation

1 9.3 17000 N90 L9 5.1L/2L/ 11.4/0.9 Coagulase negative Wound Swab C/s - CONS S/O PF28700 N89 L10 staphylococcii

71000 (CONS) Protein C / Protein S (58.8%) 36900 N86 L11 Weil Felix -ve 2 8.1 25000 N37 L81 31000 14.9/1.2 No Growth Weil Felix 1 in 320 OX-K Not done 31000 N56 L14 3 8.9 28000 N77 L23 26000 19.6 /1.6 No Growth Weil Felix OX-2:1:160 Not done 26800 N74 L20 OX-19:1:160

OX-K:1:20 20300 N74 L20 4 7.9 18000 N79 L21 8000 13.9/1.1 No Growth Weil Felix -ve Not done 30000 Repeat titers after 2 weeks -ve 51000 CT Scan / MRI / EEG-normal 5 8.9 36000 N71 L36 94000 12.6/1 No Growth Weil felix -ve S/O PF

TABLE 1. Clinical Profile and Management of Patients with Purpura Fulminans

Patient Age Sex Presenting Features Complications Interventions OutcomeNo (Months)

1 18 F Fever, Rash Gangrene of digits, IV antibiotics, Plastic surgicalSkin Leisions Anticoagulants – intervention for

Warfarin gangreneAspirin

2 15 M Fever, Rash, Gangrene of Ventilation Plastic surgicalSeizures digits Extensive IV Antibiotics intervention for

skin leisions with Anticoagulants - Gangreneeschar formation low molecular

weight heparin,Warfarin

3 12 F Fever, Rash, Gangrene of digits Ventilation GoodAltered Sensorium IV Antibioticswith seizures Anticoagulants -

low molecularweight heparin,Warfarin

4 18 M Fever, Rash, Gangrene of digits Ventilation GoodAltered Sensorium Involuntary movements IV Antibioticswith seizures Extra pyramidal Anticoagulants -

symptoms low molecularweight heparin,Warfarin

5 15 M Fever, Rash, Gangrene of digits IV Antibiotics GoodAltered Sensorium Anticoagulationwith seizures with low molecular

weight heparin

Spectrum of Purpura Fulminans

Indian Journal of Pediatrics, Volume 76—January, 2009 89

the majority of the cases of PF, while gram negativeorganisms are the commonest cause of the acuteinfectious variety.

In children, this rapidly progressive illness is usuallyassociated with severe bacterial or viral infections.4 Theimmaturity of Protein C system and factor v G1691Amutation in children who are <4 years of age maycontribute to the rapid and more development frequentpathogenesis of PF.4, 5 In our case series the children withPF were younger than 2 years. The onset has beendescribed following such diseases as meningococcemia,varicella, scarlet fever, streptococcal pharyngitis,pneumococcal, vibrio bacteremia rubella and otherexanthemata.1, 2 Staphylococcal sepsis and rickettsiosishave been reported as rare causes of PF.6, 7

The pathogenesis of PF is not been clearly established.PF is often described as Schwartzman like reaction. Thedisease begins suddenly with development ofprogressively enlarging, well-demarcated purplish blackareas of hemorrhagic cutaneous necrosis as seen in mostof our children.9 Chills, fever, lethargy, shock and comamay accompany the massive hemorrhage and gangrene.Affected areas are painful and indurated. Althoughinitially sterile, secondary infection of the gangrenoustissue may occur. Death may occur within 8-72 hrs.

Laboratory abnormalities that should be performedinclude a full blood count, PT, PTT, fibrinogen and fibrindegradation products. Anemia, leucocytosis andthrombocytopenia were present in all cases. Anemia is afeature of the disease and results from a combination oftissue extrvasation, external loss and microangiopathichemolysis. Leucocytosis with shift to left is common andprobably related to tissue necrosis.1, 2 In our case seriestwo children had raising Weil Felix titers.

Early recognition of PF and immediate initiation ofrational therapy can reduce the fatality rate and possiblyprevent the necessity of surgical amputation.Administration of Heparin together with large volumes ofFFP is partially effective in halting the progression of thedisease.9 Heparin therapy may limit digit necrosis whenused early and in therapeutic doses.3, 10 Low molecularweight Heparin has been found to be effective.4 Heparinshould be continued for at least 8 days. However, sincerelapse is low, there is probably no indication of long-term prophylactic therapy.3

Empirical antimicrobial therapy should necessarily bebroad to cover the wide range of bacteria that areassociated with this complication, in absence of a definitemicrobial etiology. The antibiotic should be administeredearly in the disease.2 All our children were treated withantistaphyloccocal antibiotics and inj chloramphenicolwas started in view of raised titers in Weil Felix test.

Adjunct therapies evaluated in infectious PF include

Protein C, Activated Protein C, antithrombinIII, Freshfrozen plasma, plasma exchange, tissue plasminogenactivator, heparin, dextran, topical nitroglycerin,prostacyclin, hirudin and hyperbaric oxygen.11, 12

Fasciotomies during the initial management may reducethe depth of soft tissue involvement and extent ofamputation. Auto amputation of involved extremities isrecommended to preserve some digital length andfunction.13

CONCLUSION

PF is potentially disabling and life-threatening disordercharacterized by acute onset of progressive cutaneoushemorrhage and necrosis, and disseminated intravascularnecrosis. The condition is often fatal, and survivors mayhave considerable morbidity related to loss of digits,limbs, or areas of skin. Recogition of pathophysiologicmechanism may provide a rational basis for treatment.Immediate heparinization, infusion of FFP, and early useof appropriate antibiotics may limit mortality as well asmorbidity.

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9. Michael levin, S. brain, Jaeques louis et al. Post infectiousPurpura Fulminans caused by an autoantibody directedagainst protein S. J Pediatr 1995; 127 : 355-363.

10. Kuppermann N, Inkalis SH, Salndio R. The role of Heparin inthe prevention of extremity and digit necrosis inmeningococcal Purpura fulminans. Peditr Infect Dis J 1995; 14:552-553.

11. Rentala E, Kauppila M, Seppala op et al. Protein C substitutionin sepsis associated purpura fulminans. Crit Care Med 2000; 23:2373-2378.

12. Smith OP, White B, Vaughan D. Use of Protein C concentrate,Heparin and Hemodiafiltration in Meningococcus inducedPurpura fulminans. Lancet 1997; 350 : 1590-1593.

13. Cannale ST, Ikard ST. The orthopaedic complications ofpurpura fulminans. J Bone Joint Surg 1984; 66-A: 764-769.