We report an unusual presentation of a 16 year old patient with parvovirus B19 infection. The girl was admitted to our hospital with a one week history of high fever and cervical lymphadenopathy. She complained of chronic fatigue over three months, and had been mostly bedridden, unable to visit school. On examination, a tender cervical lymph node with a diameter of 5 × 8 cm was palpable in the right cervical region. The left cervical side showed no enlargement. There was no axillary or inguinal lymphadenopathy. She had a rash on both cheeks, which anamnestically occurred intermittently before and after fever periods, so that it could not be clearly attributed to a primary infection.
Cervical ultrasound demonstrated multiple hypoechoic lymph nodes of up to 23 mm in size, with loss of normal internal structure along the jugular vein, reaching from the right jaw bone angle to the supraclavicular region (fig 1). Haematological studies revealed leucopenia (white blood cell count, 1.8 × 109/litre), thrombocytopenia (platelets, 127 × 109/litre), and a normal haemoglobin concentration (122 g/litre); in addition, erythropoesis was affected by a loss of reticulocytes. Serum analysis revealed a high lactate dehydrogenase value (778 U/litre), suggesting abnormal cell lysis. The erythrocyte sedimentation rate was raised, but C reactive protein was negative. The humoral immune response parameters were normal (IgG, 13650 mg/litre; IgA, 2940 mg/litre; and IgM, 1430 mg/litre), as were the surface antigen markers of mononuclear cells (CD3, CD4, CD8, CD4/CD8, CD2, CD16CD56+/CD3−, CD20, CD3/HLA-I, CD4/CD45RA, CD4/CD45RO, CD3/CD25, CD3/HLA-II, T cell receptor γ/δ, CD14/HLA-II).
Figure 1 Longitudinal cervical sonogram of the 16 year old girl with prolonged fatigue, demonstrating enlargement of multiple lymph nodes with diffusely reduced echogenicity and loss of typical hilar structures.
The clinical parameters were suspicious for a lymphoproliferative or haemopoetic disease. However, examination of a bone marrow aspirate showed a hypocellular bone marrow with megakaryocytopenia and reactive lymphocytes compatible with a virus infection. Similarly, the biopsy specimen of a cervical lymph node showed a nodular proliferation of sinus histiocytes with multiple apoptotic bodies without necrosis or infiltration by neutrophils (fig 2A–C).
Figure 2 Haematoxylin and eosin (H&E) and immunohistochemical staining of the lymph node specimen. (A, B) H&E staining revealed prominent nodules of histiocytes with clear cell cytoplasm and multiple apoptotic (more ...)
Although the clinical symptoms were compatible with a systemic ongoing infection, virological studies of the patient’s serum on admission for parvovirus B19 (PVB19) proteins revealed negative IgM reactivity against all investigated viral proteins NS1, VP-N, VP-C, VP-1S. NS1 is the non-structural protein 1 of PVB19. VP-N is the N-terminal half and VP-C the C-terminal half of the structural proteins VP1 and VP2, whereas VP1S is a VP1 specific segment that is distinct from VP2. In contrast, strong IgG reactivity was seen for VP-N and VP-C, whereas VP1S showed only a weak signal. Serum polymerase chain reaction (PCR) analysis for PVB19 (genotypes 1–3) was consistently negative. There was no serological evidence of Epstein-Barr virus infection.
PCR analysis of the lymph node showed a positive result for PVB19, whereas analysis for other pathogens (Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, human herpesvirus 8, Toxoplasma gondii
, Bartonella henselae
, and Mycobacterium tuberculosis
) was negative.1
PVB19 PCR was repeatedly performed by the institutes of pathology and virology of the Charité using different DNA extracts from the lymph node biopsies; the results were mostly positive and PVB19 genotype 1 was revealed.
Immunohistochemical staining for PVB19 structural proteins (VP1 and VP2) using the R92F6 antibody2
detected sporadic PVB19 reactive cells in the periphery of the histiocytic proliferations and in monocytes of the parasinal blood vessels (fig 2D).
The clinical follow up visit after two months indicated spontaneous remission of the disease.