Case Presentation: 70-year-old female with ILD and bullous pemphigoid (BP) on mycophenolate mofetil and prednisone initially presented to emergency room for hematuria and chills, where she was found to have elevated creatinine of 1.25 mg/dL (baseline creatinine 0.4 mg/dL) and prescribed a course of ciprofloxacin for hemorrhagic cystitis. She was admitted three days later due to anuria and found to have worsening creatinine of 8.50 mg/dL. She denies history of renal disease or NSAID use. Given concerns for rapidly progressive renal failure, she was started on IV methylprednisolone 1 gm daily for three days followed by prednisone 60 mg daily. Dialysis was also initiated due to worsening uremic symptoms while undergoing workup. Laboratory results included negative anti-Smith antibodies, SSA and SSB antibodies, glomerular basement membrane antibodies, anti-dsDNA antibodies, anti-myeloperoxidase antibodies, anti-serine protease 3 antibodies, anti-phospholipase A2 receptor antibodies, cryoglobulin, hepatitis B and C, and HIV. Her ANA was positive at 1:160 with speckled pattern and c-ANCA positive at 1:320. She had serum kappa free light chains of 209.9 mg/L, serum lambda free light free light chains of 119.5, and kappa/lambda free light chain ratio of 1.76. She had normal serum C3 and C4 and unremarkable SPEP. Her CT abdomen and pelvis revealed only left renal nephrolithiasis without hydronephrosis. Her renal biopsy returned with diffuse necrotizing and crescentic glomerulonephritis (rapidly progressive glomerulonephritis [RPGN]) with predominantly C3 deposits suggesting a C3 glomerulonephropathy. For treatment of her biopsy proven C3 glomerulonephropathy, she continued on prednisone 60 mg daily, was started on cyclophosphamide 50 mg daily, and her mycophenolate mofetil dose was decreased from 500 BID to 250 mg BID. She was discharged with immunosuppression in hopes of improving her RPGN and ongoing hemodialysis.
Discussion: BP is an autoimmune and inflammatory disease with subepidermal blistering characterized by C3 and IgG deposition at the basement membrane of the epidermis [1]. C3 glomerulonephropathy can be characterized by C3 dominant deposits within renal glomeruli, likely due to defects in the alternative complement pathway such as stabilizing antibodies of C3 convertase and antibodies against factor H, which normally inhibit C3 convertase [2]. We present a unique case where a 70-year-old female with chronic BP developed RPGN secondary to C3 glomerulonephropathy while on chronic immunosuppressive therapy. To our knowledge, the coexistence of these conditions is seldom reported in literature despite similarities in pathogenesis. Most case reports that describe the coexistence of BP and glomerulopathies center around membranous glomerulopathies with the deposition of IgG or IgG and C3 [3-6]. These case reports theorize there could be cross reactivity of autoimmune mechanisms, such as antibodies, between the BP and membranous glomerulopathies. Our case is unique as it suggests C3 dominant deposition in the kidney could be related to C3 deposition in BP. Lastly, treatment of these coexistent conditions requires careful consideration of immunosuppressive therapy and dosing as seen in our case.
Conclusions: This is a rare case of the coexistence of BP and C3 glomerulonephropathy associated RPGN. Further investigation of whether these two conditions are directly related in pathogenesis and association is warranted.