Human parvovirus B19 infection: Immunohistochemical and electron microscopic studies of skin lesions

Erythema infectiosum is known to be caused by human parvovirus B19 and shows characteristic clinical skin manifestations in children, although adult cases of human parvovirus B19 infection do not always show such characteristic features. Recently, we experienced an epidemic adult cases of human parvovirus B19 infection and examined the erythematous skin lesion by immunohistochemistry and electron microscopy to clarify the pathogenesis of the skin manifestations. Light microscopic examination showed slightly irregular-shaped vessels in the dermis. By immunohistochemistry, using anti-human parvovirus B19 monoclonal antibody, positive reactions were found in endothelial cells. No immunoglobulins were found, but C3 deposits were present in the perivascular areas. By electron microscopy, virus particles were found in the cytoplasm of endothelial cells. An inflammatory reaction due to the direct human parvovirus B19 infection in dermal vessels seems to be an important factor in the pathogenesis of the skin manifestations.     

Acute generalized exanthematous pustulosis in hypercalcemia

BACKGROUND: We report a case of typical exanthematous pustulosis rash that was particularly severe both clinically and biologically. Laboratory tests led to the diagnosis of acute parvovirus B19 infection. CASE REPORT: A 23-year-old man with no past medical history developed fever with an erythematous pustulosis rash predominantly involving the folds. Blood cell count revealed hyperleukocytosis. There was no previous drug intake. This skin reaction was associated with severe systemic manifestations including hypovolemic shock, and hematologic and metabolic disturbances. Virology tests revealed acute parvovirus B19 infection. The hospital physician caring for this patient also presented evidence of acute parvovirus B19 infection. DISCUSSION: The clinical features and the course of this skin eruption were typical of generalized exanthematous pustulosis. We discuss the rare viral causes of acute generalized exanthematous pustulosis and compare our case with a previously reported case of acute generalized exanthematous pustulosis with mononucleosic syndrome in a patient with no prior drug intake. The clinical and biological manifestations of this case were similar to drug hypersensitivity syndrome.     

Gloves and socks syndrome associated with parvovirus B19 infection

The spectrum of disease caused by parvovirus B19 infection ranges from asymptomatic to a serious disease. Parvovirus B19 plays a role in the pathomechanism of gloves and socks syndrome, erythema infectiosum, acute polyarthralgia, aplastic crisis in persons with hemolytic anemia, and birth defects. Gloves and socks syndrome has an acute febrile course. Painful edema of hands and feet, and numerous small confluent petechiae in the same localization are the most characteristic signs. Blisters and erosions may occur in oral mucosa. General discomfort and arthralgia accompany skin lesions. The disease tends to be self-limiting. A typical case of gloves and socks syndrome in a 36-year-old woman is reported. Serological tests disclosed the parvovirus B19 infection, confirming the causal relationship between the syndrome and this infection.     

Parvovirus B19 infection presenting concurrently as papular–purpuric gloves‐and‐socks syndrome and bathing‐trunk eruption

Parvovirus B19 infection can cause a wide range of cutaneous manifestations, including papular–purpuric gloves‐and‐socks syndrome (PPGSS) and petechial bathing trunk eruption. We report a case of an immunocompetent woman with a primary parvovirus B19 infection presenting as concurrent PPGSS and petechial bathing trunk eruption. Parvovirus B19 seroconversion was confirmed several days after the onset of the clinical manifestations. The coexistence of these two cutaneous manifestations of primary parvovirus B19 infection has rarely been reported in the literature. It is important to recognize parvovirus B19 infection early, based on the cutaneous manifestations, to avoid potentially serious systemic complications in susceptible individuals.     

Sensitive and rapid diagnosis of human parvovirus B19 infection by loop-mediated isothermal amplification

BACKGROUND: Human parvovirus B19 (B19) infections exhibit various skin manifestations that are similar to and hence hard to distinguish from many other skin diseases. The virological diagnosis of B19 infection is usually based on time-consuming serological tests and polymerase chain reaction (PCR). OBJECTIVES: In this study, a DNA amplification method, loop-mediated isothermal amplification (LAMP), was used for the diagnosis of B19 infection and was compared with PCR. METHODS: Ten patients with acute B19 infection and 16 patients with other skin diseases were enrolled. Sera and pharyngeal swabs were used directly as the templates in LAMP. The LAMP reaction was carried out at 63 degrees C for 1 h in a heat block. The reaction products were judged visually, by adding SYBR Green I into the tubes, and by gel electrophoresis. RESULTS: B19 DNA was detected by LAMP in 10 sera and all of seven tested pharyngeal swabs of 10 patients with acute B19 infection but not in samples from 16 patients with other skin diseases. The results were in agreement with those obtained by PCR except for one case. The reason for the single discrepancy may be that the sensitivity of LAMP is 10(2) times higher than PCR. CONCLUSIONS: Detection of B19 DNA by LAMP in serum and especially in the pharynx is a rapid and convenient method for the diagnosis of acute B19 infection.     

Increased prevalence of human parvovirus B19 DNA in systemic sclerosis skin

BACKGROUND: Human parvovirus B19 is a small, single-stranded DNA virus encoding two structural capsid proteins and a nonstructural protein. It is the aetiological agent of erythema infectiosum and transient aplastic crisis in patients with haemolytic anaemia, and has been associated with fetal death, arthritis and chronic anaemia. In recent years, the possible involvement of parvovirus B19 in systemic sclerosis (SSc) has been reported. OBJECTIVES: To determine whether human parvovirus B19 DNA can be detected in SSc skin tissue specimens. METHODS: Normal subjects (n = 97) and patients with SSc (n = 48), systemic lupus erythematosus (n = 16), dermatomyositis (n = 8), morphoea (n = 6) and graft-versus-host disease (n = 8) were studied. Crude DNA was extracted from skin tissue specimens. We attempted to determine whether human parvovirus B19 could be detected in the skin of SSc using nested polymerase chain reaction (PCR). PCR amplification was performed with specifically designed first and second primer pairs for parvovirus B19 DNA. RESULTS: After the first PCR, the occurrence rate of parvovirus B19 DNA in SSc skin tissues (36 of 48, 75%) was significantly elevated in comparison with that in normal controls (50 of 97, 52%) (P < 0.01). After the second PCR, the occurrence rate of parvovirus B19 DNA in SSc skin tissues (36 of 48, 75%) was significantly elevated compared with that in normal controls (53 of 97, 55%) (P < 0.02). The occurrence rates in the other diseases showed no significant difference from that in normal controls. CONCLUSIONS: The increased prevalence of human parvovirus B19 DNA in SSc skin showed the possibility that the virus may be involved in the formation of skin tissue abnormalities in the disease.     

Acute heart failure associated with human parvovirus B19 infection

We report a patient with acute heart failure due to human parvovirus B19 infection. The patient was a 36-year-old man with polyarthralgia, fatigue and swelling of his upper eyelids and all four limbs. These symptoms disappeared, but 5 days after the first consultation, the patient presented with severe exertional dyspnoea, chest pain and swelling of his whole body. Erythema was observed on the skin of hands, fingers and abdomen. Pleural and pericardial effusion, ascites and hepatosplenomegaly were detected. Laboratory examination showed positive results for anti-human parvovirus B19 IgM and B19 DNA in the serum. A diagnosis of acute heart failure by pericarditis caused by B19 was made. This case report suggests that B19 should be considered as a cause of acute heart failure through acute pericarditis.     

Secondary syphilis in persons infected with and not infected with HIV-1: a comparative immunohistologic study.

To better understand the cutaneous immune response to Treponema pallidum, we performed an immunohistologic study of skin biopsies from a total of 11 patients with secondary syphilis; biopsies from five persons infected with HIV-1 were included in the analysis to assess at the tissue level the impact of concomitant HIV-1 infection on disease expression. In all of the biopsies, staining for HLA-DR, a marker for cellular activation, was observed among infiltrating leukocytes, dermal vascular endothelial cells, and keratinocytes. Infiltrating mononuclear cells stained positively for CD4 or CD8, with CD4+ cells always being in the majority. Surprisingly, most of the CD4+ cells had histiocytic, rather than lymphocytic, morphologic characteristics. Immunostaining for CD14 confirmed that these cells were monocytic in origin, whereas immunostaining for CD3 revealed that the lymphocytes were predominantly CD8+ cytotoxic T cells. B cells were not detected despite the presence of variable numbers of plasma cells in all specimens. By immunofluorescence, all of the specimens demonstrated perivascular deposition of immunoglobulins, complement, or fibrinogen; linear staining at the dermal-epidermal junction also was observed in most of the specimens. No differences in immunocytochemical or immunofluorescence staining patterns were observed between the specimens from patients who were HIV positive and patients who were HIV negative. In addition to providing a more precise definition of the infiltrating cells in syphilitic lesions, our results, taken as a whole, indicate that cellular immune processes are largely responsible for the development of cutaneous manifestations during syphilitic infection and that coinfection with HIV-1 has little discernible effect on the cutaneous response to T. pallidum.     

Detection of cytomegalovirus infection in a patient with febrile ulceronecrotic Mucha-Habermann''s disease

BACKGROUND: Febrile ulceronecrotic Mucha-Habermann's disease (FUMHD) is a severe and very rare variant of pityriasis lichenoides et varilioformis acuta, which is characterized by large coalescing, and ulceronecrotic maculopapules or plaques. Morphological changes of the skin accompanied by persistent high fever and several constitutional symptoms have suggested virus infection in patients with FUMHD. However, the available information of viral origin is limited. In this study we investigated the relationship of cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), type I human T-cell lymphotropic virus (HTLV-I), and parvovirus B19 (PVB19) with FUMHD in a Taiwanese patient. METHODS: The existence of CMV, EBV, HHV8, HTLV-I, and PVB19 was determined by polymerase chain reaction (PCR). The presence of CMV in the endothelial cells was characterized by in situ hybridization (ISH) and immunohistochemistry (IHC). RESULTS: Serologic immunoglobulin to CMV and IHC identification of CMV late gene in the biopsy specimen indicated that the patient was infected with CMV. Detection of CMV was confirmed by PCR and ISH. CONCLUSIONS: These results indicate that FUMHD is associated with dermal CMV manifestation. Nonetheless, the induction mechanism of FUMHD with CMV infection has yet to be determined.     

Parvovirus B19: a review

Infection with parvovirus B19 may result in a wide range of dermatologic manifestations. The specific skin findings include erythema infectiosum and papular purpuric "gloves-and-socks" syndrome. The nonspecific findings include reticular erythema, maculopapular eruptions, and petechiae and purpura, as well as other less frequently described findings. Associations with other dermatologic diseases, such as erythema multiforme and erythema nodosum, also have been described. A role in the pathogenesis of various collagen vascular disorders has been suggested and is under investigation. The diagnosis of infection rests on the typical clinical findings. Whenever parvovirus B19 infection is diagnosed, the physician must ensure that neither the patient nor his or her contacts is a member of certain vulnerable populations. In these populations, infection with parvovirus B19 may result in devastating complications. The vulnerable populations include those with hematologic disease, immunosuppressed patients, and pregnant women. Treatment of infection in the healthy immunocompetent individual is asymptomatic, and the acute infections typically resolve without complications.     

Detection of perforin and granzyme B mRNA expressing cells in lichen sclerosus

Granzyme B and perforin messenger RNA (mRNA) expression has been shown to be a specific in vivo activation marker for cytotoxic cells. The aim of this study was to assess the contribution of cell-mediated cytotoxicity in the pathogenesis of lichen sclerosus. In situ hybridization and immunohistochemistry were performed on serial tissue sections of lesional skin biopsies and normal skin as control. Immunohistochemical staining showed that the cellular infiltrate of diseased skin consisted predominantly of T cells (CD3+) and some B cells (CD20+). Among T cells CD4+ and CD8+ cells were found in about equal numbers. In normal skin samples perforin and granzyme B mRNA expressing cells were only rarely found. In contrast, in biopsies from diseased skin a high percentage of infiltrating cells expressed mRNA for perforin and granzyme B. The perforin and granzyme B expressing cells were found in the dermal infiltrate and intraepidermally in close proximity to keratinocytes suggesting in situ activation of these cells. These findings provide evidence that cell-mediated cytotoxicity plays a significant role in tissue destruction in lichen sclerosus.     

Prevalence and significance of human parvovirus variants in skin from primary cutaneous T cell lymphomas, inflammatory dermatoses and healthy subjects

Primary cutaneous T cell lymphomas (CTCL) represent a heterogeneous group of T lymphomas. Virus involvement in CTCL pathogenesis has been extensively investigated, but no data are available as to a causative role of parvovirus B19. The prevalence of parvovirus variants (B19, LaL1/K71, V9) was investigated by using two nested PCRs and a genotype-2 semiquantitative PCR (Q-PCR). Parvovirus DNA was detected in similar percentage in healthy skin controls (40%; n = 42), inflammatory dermatoses (ID) (41%; n = 80) and CTCL (34%; n = 76). Among variants, genotype-2 was more prevalent in ID (26%) and CTCL (22%) than in normal skin (14%; p < 0.05). genotype-3 was never found in normal skin and was rare in ID. The only four pathological skin samples with a quantifiable genome copies/μg DNA values in Q-PCR were ID. In conclusion, despite the skin represent a reservoir for genotype-1, parvovirus infection is not involved in the etiopathogenesis of CTCL.     

Langerhans cells in various benign and malignant pigment-cell lesions of the skin

Summary We used immunohistochemistry to study Langerhans cells (LCs) and the composition of the dermal inflammatory infiltrate both in normal skin and in biopsies from various benign and malignant pigment-cell lesions. In normal skin and most benign pigment-cell lesions, epidermal LCs are regularly distributed. OKT₆-Positive cells outnumber the OKIa-positive cells. The inconspicuous dermal infiltrate studied in these biopsies was composed of helper and suppressor/cytotoxic T cells and some dermal LCs. More epidermal LCs with an abnormal cytologic presentation were found in a halo naevus and in the radial growth part of primary malignant melanomas. This finding was associated with a dermal infiltrate composed of suppressor/cytotoxic T cells, suggesting a defense mechanism of the host towards abnormal melanocytes. Epidermal LCs were rare in the central part of the biopsies which showed a primary malignant melanoma in its vertical growth. A dermal inflammatory infiltrate was absent in that area. These findings are interpreted as the morphologic expression of a damaged immune system.F. Facchetti is on leave from Istituto di Anatomia Patologica, Spedali Civili di Brescia, Brescia, Italy     

A distinctive cutaneous reaction pattern indicative of infection by reactive arthropathy-associated microbial pathogens: the superantigen ID reaction

The two major cutaneous expressions of infective states are infections of the skin by viable organisms and immunological responses to nonviable microbial antigens or, in the case of molecular mimickry, their human analogues. These immunological responses are designated as cutaneous id reactions, and manifest a histomorphology similar to that seen at the primary infective site. This study presents the clinical and histological findings in 16 patients who developed skin eruptions associated with extracutaneous or systemic infections. There was a striking female predominance; patients ranged in age from 10 to 78 years. The majority of cases manifested skin lesions which clinically resembled Sweet's syndrome, erythema multiforme and/or erythema nodosum. Fever, arthralgia, oligoarthritis, mucosal ulcers of the mouth and/or genital tract and uveitis were additional features in some cases. Isolated clinical presentations included a petechial rash in a stocking and glove distribution, papular dermatitis, a morbilliform eruption and annular erythema. Among the medical and family histories were atopy and stigmata associated with connective tissue disease (CTD). Two patients were ingesting drugs with known immune dysregulating properties. Skin biopsies showed focal lymphocytic interface dermatitis, a diffuse interstitial histiocytic infiltrate, and a mononuclear cell predominant vascular reaction which in some cases represented vasculitis by virtue of manifesting concomitant luminal or mural fibrin deposition. Eosinophils, eczematous alterations, and papillary dermal edema were identified in a minority of cases. All patients had evidence of a prior or concurrent infection, based on either positive IgM serology for specific microbes or cultures. Among the implicated pathogens were cytomegalovirus, parvovirus B19, streptococcus, mycoplasma, klebsiella, and Borrelia burgdorferi. All of these organisms are among those associated with reactive arthritis, a phenomenon that was seen in some cases. The histology suggested florid cell mediated immunity (CMI), which the authors attributed to the superantigen properties held by the aforesaid pathogens. Skin lesions and constitutional symptoms resolved quickly with antimicrobial therapy in 7 of 9 cases causally linked to bacteria. Spontaneous resolution occurred in 5 of 6 virally mediated eruptions. The other 4 patients were given topical steroids or prednisone; these included 1 patient with Borrelia burgdorferi infection and 1 patient with radiographic evidence of pneumonia who was never cultured, 1 patient with parvovirus B19 infection, and 1 patient with pneumococcal pneumonia and concomitant sarcoidosis. It is the authors' belief that the eruptions seen in these patients may in part reflect a genetic or iatrogenic predis-position to respond excessively to certain infectious triggers.     

Distribution of interleukin-2 receptor bearing lymphocytes in the skin. A comparative study of allergic and irritant contact dermatitis, tuberculin reaction and cutaneous T cell lymphoma

The tissue distribution of T cells and interleukin-2 receptor bearing (Tac+) lymphocytes was studied immunohistochemically in frozen sections of biopsies from inflamed skin. In skin lesions caused by irritant or immunologic stimuli, relatively few (less than 5%) of the total dermal infiltrating T cells were Tac+, but in both types of conditions the Tac+ cells showed a predeliction for the epidermis. In skin lesions from patients with cutaneous T cell lymphoma a relatively high proportion of dermal T lymphocytes were Tac+. Tac+ as well as Tac- T lymphocytes may thus migrate to a tissue secondary to several different stimuli. The demonstration of a non-random distribution of Tac+ lymphocytes in the non-malignant inflammatory conditions in the present study indicate that the epidermis may have a special role in the activation of T lymphocytes.     

Parvovirus B19–Associated Microvesicular Eruption

We report on a 3‐year‐old girl with a microvesicular generalized rash in whom primary infection by parvovirus B19 was demonstrated by seroconversion. To our knowledge, this is the first instance of an eruption arising from parvovirus B19 with this peculiar clinical pattern.