Indian Journal of Pathology and Microbiology

CASE REPORT
Year
: 2016  |  Volume : 59  |  Issue : 1  |  Page : 110--112

Severe anemia due to parvovirus B19 in a silver haired boy


Nishant Verma1, Archana Kumar1, Rashmi Kushwaha2,  
1 Department of Pediatrics, King George's Medical University, Lucknow, Uttar Pradesh, India
2 Department of Pathology, King George's Medical University, Lucknow, Uttar Pradesh, India

Correspondence Address:
Nishant Verma
502/B, Halwasiya Lorepur Residency, New Hyderabad, Lucknow - 226 007, Uttar Pradesh
India

Abstract

Griscelli syndrome (GS) is a rare autosomal recessive immunodeficiency disorder in which the affected children present with characteristic silvery-white hairs. The hair microscopy of these children is characteristic and is helpful in differentiating GS from Chediak-Higashi syndrome which also presents with immunodeficiency and silver hairs. We report a 17-month-old boy with GS type 2 who presented with severe anemia. Bone marrow examination of the child suggested parvovirus B19 as the cause of severe anemia, which was later confirmed by DNA polymerase chain reaction.



How to cite this article:
Verma N, Kumar A, Kushwaha R. Severe anemia due to parvovirus B19 in a silver haired boy.Indian J Pathol Microbiol 2016;59:110-112


How to cite this URL:
Verma N, Kumar A, Kushwaha R. Severe anemia due to parvovirus B19 in a silver haired boy. Indian J Pathol Microbiol [serial online] 2016 [cited 2021 Oct 27 ];59:110-112
Available from: https://www.ijpmonline.org/text.asp?2016/59/1/110/178228


Full Text

 INTRODUCTION



Griscelli syndrome (GS), Chediak-Higashi syndrome (CHS), and Elejalde syndrome (ES) are the three most common genetic diseases which can present with silvery-white hairs in children. [1] Children with GS and CHS also suffer from immune dysfunction, predisposing them to recurrent infections, whereas children with ES have a normal immune function. [2] In this present report, we describe a child with GS type 2 who presented with severe anemia. Anemia in GS type 2 is most commonly due to hemophagocytosis during the accelerated phase of the disease. However, we found an unusual cause for severe anemia in our case after detailed pathological and microbiological investigations.

 CASE REPORT



A 17-month-old male child born of nonconsanguineous parentage was referred for evaluation of severe anemia. The child had a history of recurrent febrile episodes since 3 months of age, with two hospitalizations until now (one at 3 months age for pneumonia, and other at 16 months age for gastroenteritis). The antenatal and perinatal histories of the child were uneventful, and his development was also age appropriate. There was no history of transfusions received in the past.

On examination, the child had severe pallor and a characteristic appearance with silvery-white colored hairs, eyebrows, and eyelashes and light-colored skin [Figure 1]. On enquiring the mother, it was known that the light-colored hair and skin had been present since birth. He was neither underweight (weight for age between –1 and –2 standard deviation [SD] according to WHO) nor wasted (weight for height between 0 and +1 SD according to WHO); however, he had moderate stunting (height for age between –2 and –3 SD according to WHO) suggestive of chronic malnutrition. He also had mild hepatosplenomegaly (liver - 2 cm, spleen - 3 cm below costal margin). Neurologic, cardiovascular, and ophthalmologic examinations were normal.{Figure 1}

On reviewing the family history, it was found that the first issue of the parents was a stillborn male, who had silver colored hairs similar to the proband. The second issue was a normal female who is now 9 years old and healthy. The third issue was a male child, who also had silver colored hairs and frequent infections but could not be evaluated as he died at 9 months age.

Investigations of the proband have revealed severe anemia with hemoglobin 5.5 g/dl. The total leukocyte count (TLC) and platelet counts were normal (TLC 10,600/mm 3 ; absolute neutrophil count 1700/mm 3 ; platelet count 3.1 L/mm 3 ). Peripheral blood smear showed moderate anisopoikilocytosis and was notable for the absence of giant granules in the neutrophils. The corrected reticulocyte percentage was 1.8%. Liver and kidney function tests were normal. The levels of serum triglycerides, cholesterol, ferritin, and plasma fibrinogen were normal. A contrast-enhanced computed tomography scan of the head was done, which was unremarkable. Light microscopy of scalp hair showed patchy distribution of large aggregates of melanin pigment along the hair shaft [Figure 2].{Figure 2}

Based on the above clinical and laboratory workup, a diagnosis of GS type 2 was made. Genetic testing could not be done due to unavailability. It was thought that the severe anemia seen in the child was due to the accelerated phase of the disease. So, a bone marrow aspiration was done to look for hemophagocytosis. The bone marrow did not reveal hemophagocytosis and instead it showed an absolute reduction in the number of erythroid precursors with the presence of giant pronormoblasts with intranuclear inclusions suggestive of parvovirus B19 (B19V) infection [Figure 3]. The presence of B19V infection was then confirmed by positive anti-B19V IgM antibody and positive real-time polymerase chain reaction (PCR) for B19V DNA in peripheral blood. The child was transfused one unit of packed red blood cells after which his hemoglobin increased to 11 g/dl.{Figure 3}

Parents of the child were counseled about the nature of the disease, its prognosis, and the therapeutic options (bone marrow transplant), but because of financial constraints, only supportive treatment was given. The child continued to come for his regular follow-up visits for the next 7 months. During this period, he had one more episode of pneumonia and diarrhea requiring hospitalization. But, there was no recurrence of anemia and no further blood transfusions were required.

 DISCUSSION



In the present case report, we have described a child with GS type 2 with severe anemia due to parvovirus B19 infection. This association has not been described earlier in the literature. GS is a rare autosomal recessive, multisystem disorder, which was first described in 1978. [3] GS is classified into three subtypes based on the genetic loci and the clinical features. While hypopigmented hairs and skin are common to all subtypes, GS1 (caused by a mutation in the MYOSIN5A gene located on chromosome 15q21) presents primarily with neurologic impairment, GS2 (caused by mutation in the RAB27A gene located on chromosome 15q21) presents with immunological dysfunction and multisystem involvement, and GS3 (caused by mutation in the gene encoding MLPH) is the mildest variety which has only hypomelanosis. [4],[5] Of all the subtypes, GS2 is the most common while GS3 is the least common. There are 12 case reports of GS2 and none of GS1 or 3 from India. [5],[6]

The original description of GS2, given by Griscelli et al. in 1978, was that of a "syndrome associating partial albinism and immunodeficiency." [3] GS2 is caused by mutation in RAB27A gene located on chromosome 15q21. RAB27A is a member of the Rab family of small GTPase proteins and plays a crucial role in pigment transport as well as granule exocytosis in cytotoxic T-lymphocytes. [7] Therefore, mutation in RAB27A gene leads to pigmentary abnormalities as well as variable degree of immunodeficiency. Children with GS2 present with silvery scalp hair and eyelashes, hypopigmented areas in the fundus, and light-colored skin since birth and are prone to frequent pyogenic infections of the skin and internal organs. CHS is a close differential diagnosis of GS2, because it also presents with albinism and immunodeficiency, but the characteristic findings on hair microscopy (patchy distribution of large aggregates of melanin pigment along the hair shaft in GS versus evenly distributed melanin granules of regular diameter in CHS) and absence of giant granules in the neutrophils ruled out CHS in the index case.

Another important feature of GS2 is the accelerated phase of the disease which has its onset between 4 months and 4 years of age. [8] It is caused by uncontrolled T-lymphocyte and macrophage hyperactivation, resulting in hemophagocytic lymphohistiocytosis (HLH). This phase is clinically characterized by anemia, lymphadenopathy, hepatosplenomegaly, and laboratory evidence of histiocytic infiltration such as pancytopenia, elevated triglycerides, and marrow showing hemophagocytosis. Once the disease enters the accelerated phase, it is rapidly fatal within 1-4 years. Allogeneic bone marrow transplantation offers the only curative treatment in this disease. [9] In the present report, the child with GS2 presented with severe anemia and hepatosplenomegaly at 17 months of age. The reason for these findings was initially thought to be HLH, but the bone marrow revealed red cell aplasia secondary to B19V infection. Moreover, there was no other laboratory evidence of HLH in this child (normal serum ferritin, triglyceride, plasma fibrinogen, and normal platelet and WBC counts).

B19V is a single-stranded DNA virus having a unique tropism for human erythroid progenitor cells. [9] Although decrease in hemoglobin of greater than 1 g/dl is rare in healthy children infected with parvovirus B19, children who are immunocompromised (like the index case) are at risk of chronic B19V infection leading to persistent severe anemia. [10] The diagnosis of severe anemia due to B19V is suspected if the bone marrow aspirate demonstrates pure red cell aplasia with the presence of giant pronormoblasts and intranuclear inclusions. Confirmation of the diagnosis can be done by demonstrating B19V DNA using PCR. [9] Commercially available intravenous immunoglobulin (IVIG) preparations are a good source of antibodies against B19V, and their use may be considered in immunodeficient patients with severe anemia due to chronic B19V infection. [10] IVIG was not used in the index case because there was no recurrence of anemia in follow-up.

 CONCLUSION



GS2 is a rare primary immunodeficiency disorder which is underreported from developing countries because of lack of clinical suspicion and inadequate diagnostic facilities. It should be suspected in any child who presents with the characteristic silver hair and history of recurrent infections suggestive of immunodeficiency. The present report also highlights the fact that any immunodeficient child who presents with severe anemia should be investigated for B19V infection. If found infected, IVIG may be beneficial in this setting by neutralizing the virus.

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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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