A case of pathologically confirmed streptococcal infection-related IgA vasculitis with associated glomerulonephritis and leukocytoclastic cutaneous vasculitis

Abstract

We report the case of an 80 year-old woman who developed bilateral lower extremity purpura and renal impairment with proteinuria a few days after a transient fever (day 0). High levels of both anti-streptolysin-O antibody (ASO) and anti-streptokinase antibody (ASK), as well as low levels of coagulation factor XIII in serum were noted. Skin biopsy was performed and showed a leukocytoclastic vasculitis with deposition of IgA and C3 in the cutaneous small vessels, indicating IgA vasculitis in the skin. After initiation of oral prednisolone, the skin lesions showed significant improvement. However, renal function and proteinuria gradually worsened from day 12. Kidney biopsy was performed on day 29, which demonstrated a necrotizing and crescentic glomerulonephritis with mesangial deposition of IgA and C3. In addition, the deposition of galactose-deficient IgA1 (Gd-IgA1) was positive on glomeruli and cutaneous small vessels, indicating that the purpura and glomerulonephritis both shared the same Gd-IgA1-related pathogenesis. In addition, the association between the acute streptococcal infection and the IgA vasculitis was confirmed by the deposition of nephritis-associated plasmin receptor (NAPlr) in glomeruli. The patient was treated with steroid pulse and intravenous cyclophosphamide, in addition to the oral prednisolone treatment. Renal function and proteinuria gradually improved, but did not completely recover, as is typically seen with courses of IgA vasculitis in the elderly. In this case, the streptococcal infectionrelated IgA vasculitis was confirmed pathologically by the deposition of both NAPlr and Gd-IgA1 in glomeruli, as well as Gd-IgA1 in the cutaneous small vessels.

Keywords: Gd-IgA1; IgA vasculitis; NAPlr; Streptococcal infection.

Fig. 1

The clinical time course. The serum creatinine (sCr, mg/dl: blue line), the serum CRP (mg/dl: black line), and urinary protein (UP/Cre: orange line) were shown. PSL (prednisolone), MP (methyl prednisolone), IVCY (intravenous cyclophosphamide), and UP/Cre (urinary protein/creatinine, g/gCr)

Fig. 2

Leukocytoclastic vasculitis in the skin. Leucocytoclastic vasculitis was developed in small vessels in the upper dermis of the skin (a HE staining, × 200). (b) and (c) are serial sections with HE staining (b × 600) and EMG staining (c × 600) indicated by the arrow in (a), showing infiltration of neutrophils with fine nuclear dusts into the vessel wall and perivascular area and fibrin exudation and hemorrhage

Fig. 3

Immunofluorescence findings of the skin. Immunofluorescence for IgA, C3, and galactose-deficient IgA1 (Gd-IgA1) was performed using pronase-digested paraffin specimens. The deposition of IgA (a × 200) and C3 (b × 200) were detected on the small vessels (arrowheads) in the dermis. The Gd-IgA1 was immunostained by KM55 antibody (c × 200). (d) (× 600) and (e) (× 600) were the high magnification view of the dotted square in (c). The deposition of Gd-IgA1 was detected on small vessels in the upper dermis

Fig. 4

Necrotizing and crescentic glomerulonephritis in IgA vasculitis with nephritis. Necrotizing and crescentic lesions developed in glomeruli with fibrin deposition and cellular crescent formation (a Masson staining, × 200). Mesangial proliferation was developed (arrow in b PAM staining, × 600 and arrow in c PAS staining, × 600) with fibrin exudation. In necrotizing glomerular lesion, prominent infiltration of neutrophils (arrowhead in d HE staining, × 600) also developed

Fig. 5

Immunofluorescence findings of the kidney. Immunofluorescence findings in frozen specimens of the IgG (a × 400), IgA (b × 400), IgM (c × 400), C1q (d × 400), C3 (e × 400), and C4 (f × 400) showed segmental deposition of IgA and C3 in the mesangial area. The deposition of Gd-IgA1 in paraffin specimens (g × 400) was noted on the mesangial and the glomerular capillary walls. The deposition of NAPlr in glomeruli was detected in frozen specimens (h × 400) that might be positive on infiltrated neutrophils (arrowhead) and mesangial areas (arrow)