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CORRESPONDENCE
Year : 2021  |  Volume : 66  |  Issue : 2  |  Page : 201-203
An unusual occurrence of protein C deficiency and cytomegalovirus infection in a case of purpura fulminans


1 Department of Pediatrics, Lok Nayak Hospital and Maulana Azad Medical College, New Delhi, India
2 Division of Genetics and Metabolism, Department of Pediatrics, Lok Nayak Hospital and Maulana Azad Medical College, New Delhi, India

Date of Web Publication16-Apr-2021

Correspondence Address:
Seema Kapoor
Division of Genetics and Metabolism, Department of Pediatrics, Lok Nayak Hospital and Maulana Azad Medical College, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.IJD_463_19

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How to cite this article:
Sait H, Singh R, Kapoor S. An unusual occurrence of protein C deficiency and cytomegalovirus infection in a case of purpura fulminans. Indian J Dermatol 2021;66:201-3

How to cite this URL:
Sait H, Singh R, Kapoor S. An unusual occurrence of protein C deficiency and cytomegalovirus infection in a case of purpura fulminans. Indian J Dermatol [serial online] 2021 [cited 2021 Oct 21];66:201-3. Available from: https://www.e-ijd.org/text.asp?2021/66/2/201/313759




Sir,

Purpura fulminans (PF) is a rapidly progressive thrombotic disorder causing hemorrhagic skin infarction and disseminated intravascular coagulation (DIC). Congenital causes include defects in protein C and protein S deficiency. It is usually severe in nature and manifests in the neonatal period. We report an infant who presented with PF in the post neonatal period due to homozygous PROC gene mutation and active cytomegalovirus infection (CMV).

A 4-month-old male infant, 4th born of nonconsanguineous marriage was brought by parents with complaints of bluish black skin lesions. The lesion was first noticed by parents at the age of 2 months. The lesion gradually increased in size with central area of blueblack necrosis and eventually involved the entire abdomen, lower limb, scalp, and cannula sites [Figure 1],[Figure 2],[Figure 3]. Antenatal, perinatal period was uneventful and the family history was not significant. His anthropometric record was normal.
Figure 1: Purpura fulminans over the scalp

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Figure 2: Purpura Fulminans over abdomen

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Figure 3: Healed purpura fulminans

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Sepsis work up was negative. Initial hemoglobin recorded 7.7 g/dL, total leukocyte count 13200/mm3 and platelet of 1.64 L. Coagulation profile revealed prolonged prothrombin and activated partial thromboplastin time (>2 and 4 min), raised D-dimer (1104 ng/mL), raised lactate dehydrogenase (1395 U/L) and low fibrinogen (103 mg/dL) consistent with DIC. Autoimmune profile (complete antinuclear antibody profile, p and c antineutrophil cytoplasmic antibodies) was negative. Immunodeficiency work up revealed normal immunoglobulin profile and borderline reduced CD19+ cells (4.25%, normal range 11-45%) suggestive of B cell deficiency. serological work demonstrated IgM positivity for CMV infection. Urine polymerase chain reaction (PCR) for CMV showed the presence of 7.37 × 104 copies/mL. Thrombophilia screening was performed using AGENA Mass ARRAY platform which demonstrated high risk alleles in plasminogen activator inhibitor-1 (PAI-1) serpine (-675 5G/4G) and 5-methyltetrahydrofolate-homocysteine s-methyltransferase (MTR) (A2756G) gene. Clinical exome sequencing showed a homozygous missense variation (c.935C>T) in exon 9 of the PROC gene that resulted in the substitution of amino acid leucine for serine at codon 312. This variant is already reported to be pathogenic in literature. After stabilisation, the infant was started on valgancy clovir and also on enoxaparin that was later shifted to warfarin.

Inherited protein C deficiency (PCD) is a rare disorder that predisposes patients to thrombophilia. The disorder has variable penetrance and phenotypic expression. Purpura fulminans is one of the manifestations of PCD which presents within few days after birth. The gene responsible for PCD is PROC gene that is located on chromosome 2q13-14 and consists of 9 exons.[1] A homozygous missense variation (c.935C>T) of the PROC gene in our infant was located in exon 9, a site that is particularly significant for protein C function as it encodes the catalytic and binding site for factor Va. The infant has also shown the presence of high risk allelles of PAI-1 serpine (-675 5G/4G) and MTR (A2756G) gene which further aggravated the prothrombotic state.

In addition, CMV viral protein enhances vascular smooth muscle cell proliferation resulting in perivascular inflammation and thrombosis.[2] Along with T cell immunity, humoral immunity has an additive role of controlling viral load and limiting the severity of the disease.[3] Hence, the borderline B cell deficiency could have triggered the endothelial cell damaging effect of CMV infection and played a synergistic role in PF. Fonkoua et al.[4] reported a patient having PF due to protein S deficiency post cytomegalovirus and varicella infection. Boger[5] reported portal vein thrombosis in a 4-month-old girl due to the presence of CMV infection and inherited protein c and s deficiency.

We report a rather delayed presentation of a homozygous protein C deficiency with high risk alleles in both PAI-1 serpine and MTR gene. Recognition of CMV infection and concomitant deficiency of protein C have been sparingly reported with a pure cutaneous phenotype.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgements

We thank the parents for their support.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Baothman AA, AlSobhi E, Khayat HA, Alsulami RE, Alkahtani AS, Al-Thobyani AA, et al. A delayed presentation of homozygous protein C deficiency in a series of children: A report on two molecular defects. Clin Case Rep 2017;5:315-20.  Back to cited text no. 1
    
2.
Speir E, Modali R, Huang ES, Leon MB, Shawl F, Finkel T, et al. Potentialrole of human cytomegalovirus and p53 interaction in coronary restenosis. Science 1994;265:391-4.  Back to cited text no. 2
    
3.
Hanley PJ, Bollard CM. Controllingcytomegalovirus: Helpingthe immunesystemtake the lead. Viruses 2014;6:2242-58.  Back to cited text no. 3
    
4.
Fonkoua LK, Zhang S, Canty E, Fairfull A, Benich S, Knab A, et al. Purpura fulminans from reduced protein S following cytomegalovirus and varicella infection. Am J Hematol 2019;94:491-5.  Back to cited text no. 4
    
5.
Arav-Boger R, Reif S, Bujanover Y. Portal veinthrombos is caused byprotein C and protein Sdeficiency associated with cytomegalovirus infection. J Pediatr 1995;126:586-8.  Back to cited text no. 5
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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