Case for Diagnosis DOI: 10.1111/ddg.12384
Stenosing proctitis with subsequent colostomy placement
Peter Mayser1, Can Imirzalioglu2, Eberhard Straube3 (1) Department of Dermatology, Venereology, and Allergology – University Hospital Gießen and Marburg, Campus Gießen (2) Institute for Medical Microbiology – University Hospital Gießen and Marburg, Campus Gießen, Justus Liebig University Gießen and German Center for Infection Research (DZIF) Gießen-Marburg-Langen, Campus Gießen (3) Institute for Medical Microbiology, University Hospital Jena, Consulting Laboratory for Human Chlamydia Infections, Jena
History On his way back from a vacation in Dubai three and a half years ago, a 57-year-old man first experienced painful anal spasms accompanied by rectal hemorrhage. The only medical history was hypertension which was under control with
nebivolol. Proctoscopy revealed an ulcerating proctitis with rapidly progressive rectal stenosis, which necessitated placement of a double-barreled colostomy of the sigmoid colon two and half years later. Biopsies taken from the anorectal transitional zone at the time showed signs of a markedly florid, but in other areas also chronically granulating proctitis with mostly preserved cryptal architecture; there were no granulomas and no evidence for malignity.
Clinical Findings Proctoscopy revealed flat circular ulcers roughly 10 cm from the anus (Figure 1a). The perineal region displayed an ulceration, approximately 1 cm in diameter. The surrounding skin up to the scrotal root was erythematous and showed an infiltrated papillomatous texture (Figure 1b). Lymphadenopathy was not detectable. The patient complained about intense oozing and pruritus, especially at night. There was no weight loss or fever. He had been largely unsuccessfully treated with corticosteroid ointments and zinc paste as well as sitz baths containing tanning agents.
Figure 1 Ulcerating proctitis (a), perineal ulcer (b).
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© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1211
Case for Diagnosis Diagnosis: Lymphogranuloma venereum (LGV) proctitis
Discussion
Figure 2 Mixed inflammatory infiltrate rich in plasma cells as well as focal epithelioid granulomas (HE, x 4).
Histology A biopsy taken ventral to the ulceration showed parakeratosis, irregular acanthosis, exocytosis of neutrophils and lymphocytes, marked papillary dermal edema, dermal fibrosis, perivascularly accentuated lymphocyte and macrophage infiltration extraordinarily rich in plasma cells as well as focal epithelioid granulomas (Figure 2). PAS staining was negative.
Lab Results Further lab results: HIV and syphilis serology (TPHA; RPR): negative; HBs antigen, anti HCV: negative; cytomegalovirus IgG: positive (> 250 U/ml), IgM negative; Chlamydia trachomatis IgG antibody ELISA: 105 U/ml; Chlamydia pneumoniae IgG antibody ELISA: 189 U/ml, IgM and IgA both negative (positive > 50 U/ml); further lab results were within normal limits. A wound swab revealed massive amounts of Staphylococcus aureus.
Your diagnosis?
Positive Chlamydia trachomatis polymerase chain reaction (PCR) (hyplex ® STD Chlamydia, Amplex, Germany) in tissue samples as well as a wound swab [1–3] was instrumental in establishing the correct diagnosis. Subsequently, the genotype L2c was determined by means of major outer membrane protein (MOMP) gene based PCR. After amplification of the MOMP target (multiplex PCR kit, Qiagen, Germany), a sequencing reaction (ABI-PRISM® 3130, Applied Biosystems, USA) was performed followed by data base matching. Chlamydia trachomatis serotypes L1–L3 are the causative agents in LGV [3–6]. The current LGV epidemic among homosexual men (MSM; male sex with male) [3] in Europe and North America, primarily caused by genotype L2b [7], reveals the rectum as most frequent site of infection. The majority of these patients show an HIV coinfection or coinfections with other bacterial STI and/or hepatitis C virus. The genotype L2c identified in our patient was first detected in an MSM with severe hemorrhagic proctitis in 2011. It is a recombinant made up of an invasive L2 and a noninvasive urogenital D strain [8]. After an incubation period of 3–30 days, stage 1 LGV patients develop an ulcerating papule at the inoculation site, which goes unnoticed in 58 % of cases and spontaneously heals. In rectal involvement, such as the present case, patients may show severe anorectal pain accompanied by hemorrhage, tenesmus, and constipation, potentially imitating the clinical picture of chronic inflammatory bowel disease (especially Crohn disease and ulcerative colitis) [4, 6]. Furthermore, extraintestinal manifestations such as reactive arthritis and hepatitis have also been described [9]. In case of primary rectal lesions, the second (bubonic) stage is characterized by involvement of perirectal and paraaortal lymph nodes (LN), which – unlike primary genital infections (regional LN, in contrast to syphilis, marked by inflammation, fluctuation and at times perforation) – is difficult to detect. The most severe complication in stage 3 LGV disease is involvement of the anorectum with rectal thickening, infiltration, and stenosis, which, in our patient, required colostomy placement. Late complications are fistulas and strictures. Establishment of the diagnosis is based on DNA amplification methods from tissue as well as swabs [1–3]. Serologically, a fourfold increase in Chlamydia trachomatis-specific IgA antibody titer levels or a titer >1 : 64 [2] may be diagnostic. Serologic cross reactivity within the Chlamydia genus
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1211
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Case for Diagnosis
frequently hampers identification of the exact species. Unlike microimmunofluorescence, ELISA systems are particularly susceptible to this error. Without any clinical correlation as in the present case, mere serologic results do not allow for differentiation between a monoinfection with C. trachomatis respectively C. pneumoniae or a dual infection. Histology is nonspecific [5]. Guideline-oriented therapy consists of doxycycline 100 mg BID for 21 days, during pregnancy erythromycin 500 mg QID for 21 days [2, http://www.iusti.org/regions/ Europe/euroguidelines.htm]. Doxycycline-resistent cases have been described [10]. Asymptomatic sex partners also should be treated with doxycycline 100 mg BID for seven days. Our patient showed marked improvement of inflammatory symptoms under doxycycline 100 mg BID for six weeks. Pruritus and oozing also stopped. Two months later, colostomy reversal was performed without any c omplications. As to differential diagnoses, the most frequent causes for infectious proctitis are gonorrhea (30 %), chlamydia (19 %) and HSV 2 infections (16 %) as well as syphilis (2 %). Coinfections are common. As in our patient, the diagnosis is frequently delayed, because chronic inflammatory bowel disease comes to the fore in the diagnostic consideration. Endoscopic and also histopathologic findings are often not diagnostic in infectious proctitis. Helpful clues may be the sexual history, recent travel activities as well as frequently severe perianal secretion. Perianal ulceration can be a cardinal sign [11] and PCR performed from wound swabs may contribute to swiftly making the correct diagnosis. Conflict of interest None. Correspondence to
References 1
Markowicz M, Grilnberger E, Huber F et al. Case report: l ymphogranuloma venereum proctitis-from rapid screening to molecular confirmation of a masked sexually transmitted disease. Diagn Microbiol Infect Dis 2013; 76(4): 516–7. 2 Vries HJ, Zingoni A, White JA, Ross JD, Kreuter A. 2013 European Guideline on the management of proctitis, proctocolitis and enteritis caused by sexually transmissible pathogens. Int J STD AIDS 2013; Dec 18. [Epub ahead of print]. 3 v Krosigk A, Meyer T, Jordan S et al. Dramatic increase in lymphogranuloma venereum among homosexual men in Hamburg. J Dtsch Dermatol Ges 2004; 2(8): 676–80. 4 Lamb CA, Lamb EI, Mansfield JC, Sankar KN. Sexually transmitted infections manifesting as proctitis. Frontline Gastroenterol 2013; 4(1): 32–40. 5 Voltaggio L, Montgomery EA, Ali MA et al. Sex, lies, and gastrointestinal tract biopsies: a review of selected sexually transmitted proctocolitides. Adv Anat Pathol 2014; 21(2): 83–93. 6 Hoentjen F, Rubin DT. Infectious proctitis: when to suspect it is not inflammatory bowel disease. Dig Dis Sci 2012; 57(2): 269–73. 7 Peuchant O, Baldit C, Le Roy C et al. First case of Chlamydia trachomatis L2b proctitis in a woman. Clin Microbiol Infect 2011; 17(12): E21–3. 8 Somboonna N, Wan R, Ojcius DM et al. Hypervirulent Chlamydia trachomatis clinical strain is a recombinant between lymphogranuloma venereum (L(2)) and D lineages. MBio 2011; 2(3): e00045–11. 9 Vall-Mayans M, Caballero E, Sanz B. The emergence of lymphogranuloma venereum in Europe. Lancet 2009; 374(9686): 356. 10 Méchaï F, deBarbeyrac B, Aoun O et al. Doxycycline failure in lymphogranuloma venereum. Sex Transm Infect 2010; 86(4): 278–9. 11 Singhrao T, Higham E, French P. Lymphogranuloma venereum presenting as perianal ulceration: an emerging clinical presentation? Sex Transm Infect 2011; 87(2): 123–4.
Prof. Dr. med. Peter Andreas Mayser Universitätsklinikum Gießen und Marburg Klinik für Dermatologie, Venerologie und Allergologie – Standort Gießen Gaffkystraße 14 35385 Gießen Germany E-mail: [email protected]
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© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1211
Stenosing proctitis with subsequent colostomy placement
Peter Mayser1, Can Imirzalioglu2, Eberhard Straube3 (1) Department of Dermatology, Venereology, and Allergology – University Hospital Gießen and Marburg, Campus Gießen (2) Institute for Medical Microbiology – University Hospital Gießen and Marburg, Campus Gießen, Justus Liebig University Gießen and German Center for Infection Research (DZIF) Gießen-Marburg-Langen, Campus Gießen (3) Institute for Medical Microbiology, University Hospital Jena, Consulting Laboratory for Human Chlamydia Infections, Jena
History On his way back from a vacation in Dubai three and a half years ago, a 57-year-old man first experienced painful anal spasms accompanied by rectal hemorrhage. The only medical history was hypertension which was under control with
nebivolol. Proctoscopy revealed an ulcerating proctitis with rapidly progressive rectal stenosis, which necessitated placement of a double-barreled colostomy of the sigmoid colon two and half years later. Biopsies taken from the anorectal transitional zone at the time showed signs of a markedly florid, but in other areas also chronically granulating proctitis with mostly preserved cryptal architecture; there were no granulomas and no evidence for malignity.
Clinical Findings Proctoscopy revealed flat circular ulcers roughly 10 cm from the anus (Figure 1a). The perineal region displayed an ulceration, approximately 1 cm in diameter. The surrounding skin up to the scrotal root was erythematous and showed an infiltrated papillomatous texture (Figure 1b). Lymphadenopathy was not detectable. The patient complained about intense oozing and pruritus, especially at night. There was no weight loss or fever. He had been largely unsuccessfully treated with corticosteroid ointments and zinc paste as well as sitz baths containing tanning agents.
Figure 1 Ulcerating proctitis (a), perineal ulcer (b).
1054
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1211
Case for Diagnosis Diagnosis: Lymphogranuloma venereum (LGV) proctitis
Discussion
Figure 2 Mixed inflammatory infiltrate rich in plasma cells as well as focal epithelioid granulomas (HE, x 4).
Histology A biopsy taken ventral to the ulceration showed parakeratosis, irregular acanthosis, exocytosis of neutrophils and lymphocytes, marked papillary dermal edema, dermal fibrosis, perivascularly accentuated lymphocyte and macrophage infiltration extraordinarily rich in plasma cells as well as focal epithelioid granulomas (Figure 2). PAS staining was negative.
Lab Results Further lab results: HIV and syphilis serology (TPHA; RPR): negative; HBs antigen, anti HCV: negative; cytomegalovirus IgG: positive (> 250 U/ml), IgM negative; Chlamydia trachomatis IgG antibody ELISA: 105 U/ml; Chlamydia pneumoniae IgG antibody ELISA: 189 U/ml, IgM and IgA both negative (positive > 50 U/ml); further lab results were within normal limits. A wound swab revealed massive amounts of Staphylococcus aureus.
Your diagnosis?
Positive Chlamydia trachomatis polymerase chain reaction (PCR) (hyplex ® STD Chlamydia, Amplex, Germany) in tissue samples as well as a wound swab [1–3] was instrumental in establishing the correct diagnosis. Subsequently, the genotype L2c was determined by means of major outer membrane protein (MOMP) gene based PCR. After amplification of the MOMP target (multiplex PCR kit, Qiagen, Germany), a sequencing reaction (ABI-PRISM® 3130, Applied Biosystems, USA) was performed followed by data base matching. Chlamydia trachomatis serotypes L1–L3 are the causative agents in LGV [3–6]. The current LGV epidemic among homosexual men (MSM; male sex with male) [3] in Europe and North America, primarily caused by genotype L2b [7], reveals the rectum as most frequent site of infection. The majority of these patients show an HIV coinfection or coinfections with other bacterial STI and/or hepatitis C virus. The genotype L2c identified in our patient was first detected in an MSM with severe hemorrhagic proctitis in 2011. It is a recombinant made up of an invasive L2 and a noninvasive urogenital D strain [8]. After an incubation period of 3–30 days, stage 1 LGV patients develop an ulcerating papule at the inoculation site, which goes unnoticed in 58 % of cases and spontaneously heals. In rectal involvement, such as the present case, patients may show severe anorectal pain accompanied by hemorrhage, tenesmus, and constipation, potentially imitating the clinical picture of chronic inflammatory bowel disease (especially Crohn disease and ulcerative colitis) [4, 6]. Furthermore, extraintestinal manifestations such as reactive arthritis and hepatitis have also been described [9]. In case of primary rectal lesions, the second (bubonic) stage is characterized by involvement of perirectal and paraaortal lymph nodes (LN), which – unlike primary genital infections (regional LN, in contrast to syphilis, marked by inflammation, fluctuation and at times perforation) – is difficult to detect. The most severe complication in stage 3 LGV disease is involvement of the anorectum with rectal thickening, infiltration, and stenosis, which, in our patient, required colostomy placement. Late complications are fistulas and strictures. Establishment of the diagnosis is based on DNA amplification methods from tissue as well as swabs [1–3]. Serologically, a fourfold increase in Chlamydia trachomatis-specific IgA antibody titer levels or a titer >1 : 64 [2] may be diagnostic. Serologic cross reactivity within the Chlamydia genus
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1211
1055
Case for Diagnosis
frequently hampers identification of the exact species. Unlike microimmunofluorescence, ELISA systems are particularly susceptible to this error. Without any clinical correlation as in the present case, mere serologic results do not allow for differentiation between a monoinfection with C. trachomatis respectively C. pneumoniae or a dual infection. Histology is nonspecific [5]. Guideline-oriented therapy consists of doxycycline 100 mg BID for 21 days, during pregnancy erythromycin 500 mg QID for 21 days [2, http://www.iusti.org/regions/ Europe/euroguidelines.htm]. Doxycycline-resistent cases have been described [10]. Asymptomatic sex partners also should be treated with doxycycline 100 mg BID for seven days. Our patient showed marked improvement of inflammatory symptoms under doxycycline 100 mg BID for six weeks. Pruritus and oozing also stopped. Two months later, colostomy reversal was performed without any c omplications. As to differential diagnoses, the most frequent causes for infectious proctitis are gonorrhea (30 %), chlamydia (19 %) and HSV 2 infections (16 %) as well as syphilis (2 %). Coinfections are common. As in our patient, the diagnosis is frequently delayed, because chronic inflammatory bowel disease comes to the fore in the diagnostic consideration. Endoscopic and also histopathologic findings are often not diagnostic in infectious proctitis. Helpful clues may be the sexual history, recent travel activities as well as frequently severe perianal secretion. Perianal ulceration can be a cardinal sign [11] and PCR performed from wound swabs may contribute to swiftly making the correct diagnosis. Conflict of interest None. Correspondence to
References 1
Markowicz M, Grilnberger E, Huber F et al. Case report: l ymphogranuloma venereum proctitis-from rapid screening to molecular confirmation of a masked sexually transmitted disease. Diagn Microbiol Infect Dis 2013; 76(4): 516–7. 2 Vries HJ, Zingoni A, White JA, Ross JD, Kreuter A. 2013 European Guideline on the management of proctitis, proctocolitis and enteritis caused by sexually transmissible pathogens. Int J STD AIDS 2013; Dec 18. [Epub ahead of print]. 3 v Krosigk A, Meyer T, Jordan S et al. Dramatic increase in lymphogranuloma venereum among homosexual men in Hamburg. J Dtsch Dermatol Ges 2004; 2(8): 676–80. 4 Lamb CA, Lamb EI, Mansfield JC, Sankar KN. Sexually transmitted infections manifesting as proctitis. Frontline Gastroenterol 2013; 4(1): 32–40. 5 Voltaggio L, Montgomery EA, Ali MA et al. Sex, lies, and gastrointestinal tract biopsies: a review of selected sexually transmitted proctocolitides. Adv Anat Pathol 2014; 21(2): 83–93. 6 Hoentjen F, Rubin DT. Infectious proctitis: when to suspect it is not inflammatory bowel disease. Dig Dis Sci 2012; 57(2): 269–73. 7 Peuchant O, Baldit C, Le Roy C et al. First case of Chlamydia trachomatis L2b proctitis in a woman. Clin Microbiol Infect 2011; 17(12): E21–3. 8 Somboonna N, Wan R, Ojcius DM et al. Hypervirulent Chlamydia trachomatis clinical strain is a recombinant between lymphogranuloma venereum (L(2)) and D lineages. MBio 2011; 2(3): e00045–11. 9 Vall-Mayans M, Caballero E, Sanz B. The emergence of lymphogranuloma venereum in Europe. Lancet 2009; 374(9686): 356. 10 Méchaï F, deBarbeyrac B, Aoun O et al. Doxycycline failure in lymphogranuloma venereum. Sex Transm Infect 2010; 86(4): 278–9. 11 Singhrao T, Higham E, French P. Lymphogranuloma venereum presenting as perianal ulceration: an emerging clinical presentation? Sex Transm Infect 2011; 87(2): 123–4.
Prof. Dr. med. Peter Andreas Mayser Universitätsklinikum Gießen und Marburg Klinik für Dermatologie, Venerologie und Allergologie – Standort Gießen Gaffkystraße 14 35385 Gießen Germany E-mail: [email protected]
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© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1211
