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The Case ∣ An age-old enemy should not be forgotten
make your diagnosis
http://www.kidney-international.org & 2011 International Society of Nephrology
Kidney International (2011) 79, 924–925; doi:10.1038/ki.2011.12
The Case | An age-old enemy should not be forgotten John P. Havill1, Michael B. Kuperman2, Leandro L. Bernardo3 and Bernard G. Jaar1,3,4,5 1
Division of Nephrology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA; 2Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA; 3Department of Medicine, Good Samaritan Hospital, Baltimore, Maryland, USA; 4Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA and 5Nephrology Center of Maryland, Baltimore, Maryland, USA Correspondence: Bernard G. Jaar, Division of Nephrology, Department of Medicine, Johns Hopkins Medical Institutions, 2024 East Monument Street, Suite 2-500, Baltimore, Maryland 21205, USA. E-mail: [email protected]
Figure 1 | Diffuse, discrete, round macules measuring 5–10 mm in diameter and distributed on the trunk (a) and the palms of the hands (b).
A 20-year-old African-American male presented initially to an emergency department with pain of the right flank. He had no significant past medical history and was found to have a serum creatinine of 1 mg/dl. Physical examination was unremarkable, and workup included a negative computerized tomography of his abdomen with oral and intravenous contrast. The patient was discharged on famotidine. Owing to persistent symptoms, he presented to our emergency department 2 weeks later with a serum creatinine of 5.2 mg/dl. He denied sickle cell disease, nephrolithiasis, hematuria, recurrent urinary tract infection, and pyelonephritis. He denied use of non-steroidal anti-inflammatory drugs. On admission, physical examination was remarkable for a temperature of 37.5oC, blood pressure of 112/73 mm Hg, heart rate 87/min. Skin examination revealed a diffuse maculopapular
rash extending over the trunk and extremities and involving the palms and soles (Figure 1a and b). The remainder of the examination was significant for hepatosplenomegaly, confirmed on repeat computerized tomography scan of the abdomen without contrast. Pertinent admission laboratory data included hemoglobin 9.4 g/dl; platelets 140 000/mm3; white blood cell count 6000/mm3; blood urea nitrogen 32 mg/dl; creatinine 5.2 mg/dl; and serum albumin 2.2 g/dl, with normal liver function tests. Urinalysis had a specific gravity of 1.017; pH 6.5; white blood cell 15/hpf; red blood cell 6/hpf; and protein 4300 mg/dl; granular casts were present but no eosinophils. Urine culture was negative. Subsequent 24 h urine collection revealed 4.8 g of protein, and urine protein electrophoresis was consistent with mostly albuminuria.
What is the most likely diagnosis? SEE NEXT PAGE FOR ANSWERS 924
Kidney International (2011) 79, 924–925
make your diagnosis
JP Havill et al.: Syphilis and membranous glomerulonephritis
The Diagnosis | Membranous glomerulopathy
Figure 2 | Electron microscopy (x10 000) demonstrated diffuse small-size electron-dense deposits in the subepithelial aspect of the glomerular basement membrane, with overlying foot process effacement.
On further testing, serology for hepatitis B and C was negative; complement profile was normal. Human immunodeficiency virus serology was positive and confirmed; rapid plasma reagin was positive with titer 1:128. A diagnosis of syphilis was confirmed with a positive assay for Treponema pallidum immunoglobulins G and M antibodies. A syphilitic or human immunodeficiency virus-associated glomerulonephritis was suspected. The situation was further discussed with the patient who admitted to unprotected intercourse with male partners. A kidney biopsy showed focal acute tubular injury and diffuse interstitial inflammation containing up to 20 eosinophils per hpf. Immunofluorescence showed fine granular staining in capillary loops and mesangial space for immunoglobulin G (3 þ ), immunoglobulin M (2 þ ), C3 (2 þ ), and C1Q (1 þ ). Electron microscopy (Figure 2) demonstrated small-size electron-dense deposits in the subepithelial aspect of the glomerular basement membrane, with overlying foot process effacement. Rare subendothelial and mesangial electron dense deposits were also identified. Findings were consistent with secondary membranous glomerulopathy. The patient was treated with a single dose of intramuscular benzathine penicillin G, 2.4 million units, and supportive therapy. During hospitalization, the patient’s creatinine improved. His acute kidney injury was believed to be multifactorial because of non-oliguric acute tubular necrosis following contrast exposure and acute interstitial nephritis possibly because of famotidine.1 At follow-up, a month later, patient’s serum creatinine was 1.1 mg/dl and microalbumin-to-creatinine ratio was 172 mg/g. Skin lesions of secondary syphilis were completely resolved. The patient Kidney International (2011) 79, 924–925
was referred to an infectious disease consultant for further management of his newly diagnosed human immunodeficiency virus status. The renal lesions of syphilis were first described in the early twentieth century by Osler2 and Thompson.3 Our case demonstrates a classical glomerulopathy seen with secondary syphilis, although a variety of other lesions have been reported including mesangial proliferative glomerulonephritis, rapidly progressive crescentic glomerulonephritis, and minimal change disease.4 The Center for Disease Control reports a significant increase (2.2 to 3.8/100 000 population) in the incidence of both primary and latent syphilis from 2000 to 2007, 63% occurring in males who have had intercourse with another male, and the largest increase in the 15- to 24-year-old age group.5 The prognosis is favorable with treatment of the infection alone. Our patient had risk factors for this disease and classical skin lesions that increased our suspicion and prompted our workup. Despite its rare occurrence, syphilis associated renal diseases should still be considered in the differential diagnosis, especially in high-risk patient groups. DISCLOSURE
All the authors declared no competing interests. REFERENCES 1. 2. 3. 4. 5.
Hirayama K, Hanatsuka K, Ikeuchi T et al. Famotidine-induced acute interstitial nephritis. Nephrol Dial Transplant 1998; 13: 2636–2638. Osler W, McCrae T (eds). The Principles and Practice of Medicine. D Appleton and Company, New York and London, 1918, p. 276. Thompson L. Syphilis of the kidney. JAMA 1920; 75: 17–20. Hunte W, Ghraoui F, Cohen RJ. Secondary syphilis and nephritic syndrome. J Am Soc Nephrol 1993; 3: 1351–1355. http://www.cdc.gov/std/syphilis2008/default.htm (extracted 11 November 2010).
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http://www.kidney-international.org & 2011 International Society of Nephrology
Kidney International (2011) 79, 924–925; doi:10.1038/ki.2011.12
The Case | An age-old enemy should not be forgotten John P. Havill1, Michael B. Kuperman2, Leandro L. Bernardo3 and Bernard G. Jaar1,3,4,5 1
Division of Nephrology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA; 2Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA; 3Department of Medicine, Good Samaritan Hospital, Baltimore, Maryland, USA; 4Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA and 5Nephrology Center of Maryland, Baltimore, Maryland, USA Correspondence: Bernard G. Jaar, Division of Nephrology, Department of Medicine, Johns Hopkins Medical Institutions, 2024 East Monument Street, Suite 2-500, Baltimore, Maryland 21205, USA. E-mail: [email protected]
Figure 1 | Diffuse, discrete, round macules measuring 5–10 mm in diameter and distributed on the trunk (a) and the palms of the hands (b).
A 20-year-old African-American male presented initially to an emergency department with pain of the right flank. He had no significant past medical history and was found to have a serum creatinine of 1 mg/dl. Physical examination was unremarkable, and workup included a negative computerized tomography of his abdomen with oral and intravenous contrast. The patient was discharged on famotidine. Owing to persistent symptoms, he presented to our emergency department 2 weeks later with a serum creatinine of 5.2 mg/dl. He denied sickle cell disease, nephrolithiasis, hematuria, recurrent urinary tract infection, and pyelonephritis. He denied use of non-steroidal anti-inflammatory drugs. On admission, physical examination was remarkable for a temperature of 37.5oC, blood pressure of 112/73 mm Hg, heart rate 87/min. Skin examination revealed a diffuse maculopapular
rash extending over the trunk and extremities and involving the palms and soles (Figure 1a and b). The remainder of the examination was significant for hepatosplenomegaly, confirmed on repeat computerized tomography scan of the abdomen without contrast. Pertinent admission laboratory data included hemoglobin 9.4 g/dl; platelets 140 000/mm3; white blood cell count 6000/mm3; blood urea nitrogen 32 mg/dl; creatinine 5.2 mg/dl; and serum albumin 2.2 g/dl, with normal liver function tests. Urinalysis had a specific gravity of 1.017; pH 6.5; white blood cell 15/hpf; red blood cell 6/hpf; and protein 4300 mg/dl; granular casts were present but no eosinophils. Urine culture was negative. Subsequent 24 h urine collection revealed 4.8 g of protein, and urine protein electrophoresis was consistent with mostly albuminuria.
What is the most likely diagnosis? SEE NEXT PAGE FOR ANSWERS 924
Kidney International (2011) 79, 924–925
make your diagnosis
JP Havill et al.: Syphilis and membranous glomerulonephritis
The Diagnosis | Membranous glomerulopathy
Figure 2 | Electron microscopy (x10 000) demonstrated diffuse small-size electron-dense deposits in the subepithelial aspect of the glomerular basement membrane, with overlying foot process effacement.
On further testing, serology for hepatitis B and C was negative; complement profile was normal. Human immunodeficiency virus serology was positive and confirmed; rapid plasma reagin was positive with titer 1:128. A diagnosis of syphilis was confirmed with a positive assay for Treponema pallidum immunoglobulins G and M antibodies. A syphilitic or human immunodeficiency virus-associated glomerulonephritis was suspected. The situation was further discussed with the patient who admitted to unprotected intercourse with male partners. A kidney biopsy showed focal acute tubular injury and diffuse interstitial inflammation containing up to 20 eosinophils per hpf. Immunofluorescence showed fine granular staining in capillary loops and mesangial space for immunoglobulin G (3 þ ), immunoglobulin M (2 þ ), C3 (2 þ ), and C1Q (1 þ ). Electron microscopy (Figure 2) demonstrated small-size electron-dense deposits in the subepithelial aspect of the glomerular basement membrane, with overlying foot process effacement. Rare subendothelial and mesangial electron dense deposits were also identified. Findings were consistent with secondary membranous glomerulopathy. The patient was treated with a single dose of intramuscular benzathine penicillin G, 2.4 million units, and supportive therapy. During hospitalization, the patient’s creatinine improved. His acute kidney injury was believed to be multifactorial because of non-oliguric acute tubular necrosis following contrast exposure and acute interstitial nephritis possibly because of famotidine.1 At follow-up, a month later, patient’s serum creatinine was 1.1 mg/dl and microalbumin-to-creatinine ratio was 172 mg/g. Skin lesions of secondary syphilis were completely resolved. The patient Kidney International (2011) 79, 924–925
was referred to an infectious disease consultant for further management of his newly diagnosed human immunodeficiency virus status. The renal lesions of syphilis were first described in the early twentieth century by Osler2 and Thompson.3 Our case demonstrates a classical glomerulopathy seen with secondary syphilis, although a variety of other lesions have been reported including mesangial proliferative glomerulonephritis, rapidly progressive crescentic glomerulonephritis, and minimal change disease.4 The Center for Disease Control reports a significant increase (2.2 to 3.8/100 000 population) in the incidence of both primary and latent syphilis from 2000 to 2007, 63% occurring in males who have had intercourse with another male, and the largest increase in the 15- to 24-year-old age group.5 The prognosis is favorable with treatment of the infection alone. Our patient had risk factors for this disease and classical skin lesions that increased our suspicion and prompted our workup. Despite its rare occurrence, syphilis associated renal diseases should still be considered in the differential diagnosis, especially in high-risk patient groups. DISCLOSURE
All the authors declared no competing interests. REFERENCES 1. 2. 3. 4. 5.
Hirayama K, Hanatsuka K, Ikeuchi T et al. Famotidine-induced acute interstitial nephritis. Nephrol Dial Transplant 1998; 13: 2636–2638. Osler W, McCrae T (eds). The Principles and Practice of Medicine. D Appleton and Company, New York and London, 1918, p. 276. Thompson L. Syphilis of the kidney. JAMA 1920; 75: 17–20. Hunte W, Ghraoui F, Cohen RJ. Secondary syphilis and nephritic syndrome. J Am Soc Nephrol 1993; 3: 1351–1355. http://www.cdc.gov/std/syphilis2008/default.htm (extracted 11 November 2010).
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