Advertisement

A Case Report of Nasal Endometriosis in a Patient Affected by Behcet’s Disease

      Abstract

      We present a case of nasal endometriosis, an uncommon extrapelvic implantation of endometriotic tissue. A woman with a history of pelvic endometriosis and Behcet's syndrome was diagnosed with nasal endometriosis after episodes of perimenstrual epistaxis and nasal pain. Despite being rare, the presence of catamenial symptoms and the possibility of performing endoscopic biopsy allowed us to make the diagnosis of nasal endometriosis. The simultaneous presence of Behcet’s syndrome focused our attention on the pathogenesis and the therapeutic management of endometriosis.

      Keywords

       Discuss

      You can discuss this article with its authors and with other AAGL members at http://www.AAGL.org/jmig-19-4-11-00582
      Endometriosis is a chronic gynecologic disease defined as the presence of functional endometrial glands and stroma outside the uterine cavity. Endometriosis can be divided into pelvic and extrapelvic. Extrapelvic endometriosis has been described in virtually every organ except the spleen, and it’s a very rare condition that is associated with a considerable delay in diagnosis and morbidity [
      • Veeraswamy A.
      • Lewis M.
      • Mann A.
      • Kotikela S.
      • Hajhosseini B.
      • Nezhat C.
      Extragenital endometriosis.
      ]. The gastrointestinal and urinary tract are the most common sites of extrapelvic endometriosis, whereas other sites such as the diaphragm, thorax, central nervous system, inguinal canal, umbilicus, and perineum are extremely rare. To the best of our knowledge, a case of nasal endometriosis reported by Laghzaoui and Laghzaoui [
      • Laghzaoui O.
      • Laghzaoui M.
      Nasal endometriosis: apropos of 1 case.
      ] in 2001 is unique in the literature.
      Behcet’s disease is a rare systemic vascular autoimmune disease of unknown cause and a prothrombotic state [
      • Leiba M.
      • Sidi Y.
      • Gur H.
      • Leiba A.
      • Ehrenfeld M.
      Behçet's disease and thrombophilia.
      ]. Because Behcet’s disease lacks pathognomonic symptoms and laboratory findings, the diagnosis relies on clinical criteria, which are recurrent oral and genital ulcers, eye and skin lesions, and pathologic test positivity [
      • Leiba M.
      • Sidi Y.
      • Gur H.
      • Leiba A.
      • Ehrenfeld M.
      Behçet's disease and thrombophilia.
      ]. We present an extremely rare case of nasal localization of endometriosis in a woman previously treated for pelvic endometriosis and affected concurrently by Behcet’s disease.

      Patients and Methods

      The patient, a nulliparous 35-year-old woman, first came to our endometriosis outpatient clinic in June 2010. She has no family history of endometriosis. The patient had been diagnosed with pelvic endometriosis in 1994 after undergoing laparoscopic bilateral ovarian cystectomy that was performed in another center. After surgery she started combined oral contraceptive (COC). Six months later, during the cyclic interruption of COC, the patient reported episodes of epistaxis and nasal pain. After 5 months, her general practitioner performed nasal endoscopy that showed multiple mucosal lesions, which were partially removed. Histologic study revealed multiple islets of stroma and glandular structures of endometrium. In the meantime, the patient showed ocular, intestinal, and cutaneous symptoms associated with Behcet’s syndrome. To obtain the remission of symptoms related to nasal endometriosis and to prevent potential thromboembolic events caused by Behcet’s disease, COC was discontinued, and progestins were administered. However, the patient did not tolerate progestin therapy because of incomplete control of symptoms. A gonadotropin-releasing hormone analog therefore was used for limited periods of 6 months. The patient underwent annual gynecologic examination, transvaginal ultrasonography, and otolaryngologic evaluation, which had negative results for relapse of nasal and pelvic endometriosis.
      At the time of clinical examination in our center, the patient was under treatment with infliximab for Behcet’s disease. The patient did not complain of nasal symptoms. Regarding pelvic pain symptoms, the patient reported only dyspareunia, assigning a score of 7/10 according to the numeric rating scale. Bimanual gynecologic examination and transvaginal ultrasonography showed no signs of pelvic endometriosis. Likewise, the results of serum CA 125 and nasal endoscopy were negative.

      Discussion

      Endometriosis is a common gynecologic disease, with an estimated prevalence of 10% to 15% of women of reproductive age [
      • Signorile P.G.
      • Baldi A.
      Endometriosis: new concepts in the pathogenesis.
      ]. There are several theories that attempt to explain the pathogenesis, but none of these alone can explain all localizations of endometriosis [
      • Signorile P.G.
      • Baldi A.
      Endometriosis: new concepts in the pathogenesis.
      ,
      • Nisolle M.
      • Alvarez M.L.
      • Colombo M.
      • Foidart J.M.
      Pathogenesis of endometriosis.
      ]. The first theory, proposed by Sampson in 1927, was retrograde menstruation and cell transplantation. Endometrial cells and tissues deriving from retrograde menstruation implant into the peritoneal cavity, invade and induce a local inflammatory response, which is accompanied by angiogenesis, adhesions, fibrosis, scarring, neuronal infiltration, and anatomic distortion. Although most women have retrograde menstruation, not all of these have endometriosis; hence, it has been suggested that affected women may have an immune dysfunction that interferes with cleaning of the lesions. This theory can explain the pelvic localizations of endometriosis, but it does not explain the appearance of the disease in men, in girls before puberty, in women affected by Mayer-Rokitansky-Kuster-Hauser’s disease, or in extrapelvic sites. Furthermore, it has also been shown that endometriosis lacks characteristics of an autotransplant, because it is dissimilar to eutopic endometrium [
      • Nisolle M.
      • Alvarez M.L.
      • Colombo M.
      • Foidart J.M.
      Pathogenesis of endometriosis.
      ]. Another hypothesis is the lymphatic or hematogenous spread of endometrial cells. Following this theory, endometrium acts like neoplastic cells, invading blood and lymphatic vessels and spreading elsewhere. This theory is supported by the detection of endometrial cells in the lymph nodes and lymphovascular spaces, and it can explain the extrapelvic localizations [
      • Signorile P.G.
      • Baldi A.
      Endometriosis: new concepts in the pathogenesis.
      ]. The celomic metaplasia hypothesis, proposed by Meyer in 1919, states that the original celomic membrane undergoes metaplasia forming typical endometrial glands and stroma, perhaps under influence of environmental factors [
      • Nisolle M.
      • Alvarez M.L.
      • Colombo M.
      • Foidart J.M.
      Pathogenesis of endometriosis.
      ]. Some authors suggest the involvement of stem cells originating from bone marrow or the basal layer of the endometrium in the pathogenesis of endometriotic lesions. Indeed, it has been demonstrated that they could spread through vessels or fallopian tubes and differentiate into endometrial tissue at different anatomic sites, perhaps because of a failure of the immune system [
      • Figueira P.G.
      • Abrão M.S.
      • Krikun G.
      • Taylor H.S.
      Consider some of the publications of Hugh Taylor: stem cells in endometrium and their role in the pathogenesis of endometriosis.
      ,
      • Taylor H.S.
      • Osteen K.G.
      • Bruner-Tran K.L.
      • et al.
      Novel therapies targeting endometriosis.
      ]. Finally, a proposed cause of endometriosis is the dislocation of primitive endometrial tissue outside the uterine cavity during organogenesis, resulting from genetic and epigenetic alterations that lead to disruptions of well-balanced cellular equilibrium and interruption of some organizational events associated with the development of the neonatal uterine wall. This hypothesis is supported by the observation of ectopic endometrial tissue in early stages of embryonic development during autopsy of female fetuses. It is noteworthy that prevalence and localizations of these lesions were very similar to those of women with endometriosis [
      • Signorile P.G.
      • Baldi A.
      Endometriosis: new concepts in the pathogenesis.
      ].
      The suspicion of extrapelvic endometriosis is usually a critical step for the clinician, because of the rarity of the distant localizations [
      • Veeraswamy A.
      • Lewis M.
      • Mann A.
      • Kotikela S.
      • Hajhosseini B.
      • Nezhat C.
      Extragenital endometriosis.
      ]. However, the presence of perimenstrual pain and epistaxis in a woman of reproductive age should raise the suspicion of nasal endometriosis. In our case, as in the one described by Laghzaoui and Laghzaoui [
      • Laghzaoui O.
      • Laghzaoui M.
      Nasal endometriosis: apropos of 1 case.
      ], once the disease was suspected, outpatient endoscopic biopsy allowed us to obtain the histologic diagnosis.
      The treatment of patients with endometriosis can be medical, surgical or combined. The aim of medical therapy is to suppress the endocrine ovarian function and minimize inflammation, limiting growth and activities of ectopic estrogen-dependent endometrial cells [
      • Vercellini P.
      • Somigliana E.
      • Viganò P.
      • Abbiati A.
      • Barbara G.
      • Crosignani P.G.
      Endometriosis: current therapies and new pharmacological developments.
      ]. The surgical treatment, instead, aims to remove all visible endometriotic lesions [
      • Redwine D.B.
      • Wright J.T.
      Laparoscopic treatment of complete obliteration of the cul-de-sac associated with endometriosis: long-term follow-up of en bloc resection.
      ]. Our patient was treated with medical therapy because she had multiple nodules not completely removable by surgery. Moreover, this management is indicated to reduce the risk of pelvic endometriosis recurrence [
      • Seracchioli R.
      • Mabrouk M.
      • Manuzzi L.
      • et al.
      Post-operative use of oral contraceptive pills for prevention of anatomical relapse or symptom-recurrence after conservative surgery for endometriosis.
      ]. In our case, hormonal therapy achieved good symptoms control, although many of the distant lesions have a tendency to lose hormonal receptors and not respond to medical treatment [
      • Ueki M.
      Histologic study of endometriosis and examination of lymphatic drainage in and from the uterus.
      ]. Among the several medical options, estroprogestinic therapy is the most recommended for their safety, tolerability, and long-term efficacy. However, COC is contraindicated in women with prothrombotic conditions, as in our case. Gonadotropin-releasing hormone analog has the same efficacy of COC, but its administration must be temporary because of considerable side effects [
      • Vercellini P.
      • Somigliana E.
      • Viganò P.
      • Abbiati A.
      • Barbara G.
      • Crosignani P.G.
      Endometriosis: current therapies and new pharmacological developments.
      ]. Our patient was also taking infliximab to treat Behcet’s disease. Some evidence associates endometriosis with autoimmune diseases and suggests that immunomodulators, such as infliximab, may provide useful treatment effects for endometriosis [
      • Barrier B.F.
      Immunology of endometriosis.
      ]. On the other hand, endometriosis and autoimmune diseases are quite common chronic disorders in women, and their association may be causal. A randomized placebo-controlled trial evaluating the efficacy of infliximab in the treatment of pain associated with deep endometriosis didn’t show beneficial effects [
      • Koninckx P.R.
      • Craessaerts M.
      • Timmerman D.
      • Cornillie F.
      • Kennedy S.
      Anti-TNF-alpha treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial.
      ].
      In conclusion, distant endometriosis, including nasal endometriosis, may be explained with lymphatic or hematogenous spreading of endometrial tissue or stem cells, perhaps because of immune dysfunction. The presence of catamenial nasal pain and epistaxis in a woman of reproductive age should raise suspicion of this rare localization. New medical therapies on the basis of recent developments in the field of etiopathogenesis of endometriosis are advocated for women who can’t use estroprogestinic therapy.

      References

        • Veeraswamy A.
        • Lewis M.
        • Mann A.
        • Kotikela S.
        • Hajhosseini B.
        • Nezhat C.
        Extragenital endometriosis.
        Clin Obstet Gynecol. 2010; 53: 449-466
        • Laghzaoui O.
        • Laghzaoui M.
        Nasal endometriosis: apropos of 1 case.
        J Gynecol Obstet Biol Reprod. 2001; 30: 786-788
        • Leiba M.
        • Sidi Y.
        • Gur H.
        • Leiba A.
        • Ehrenfeld M.
        Behçet's disease and thrombophilia.
        Ann Rheum Dis. 2001; 60 (Review): 1081-1085
        • Signorile P.G.
        • Baldi A.
        Endometriosis: new concepts in the pathogenesis.
        Int J Biochem Cell Biol. 2010; 42: 778-780
        • Nisolle M.
        • Alvarez M.L.
        • Colombo M.
        • Foidart J.M.
        Pathogenesis of endometriosis.
        Gynecol Obstet Fertil. 2007; 35: 898-903
        • Figueira P.G.
        • Abrão M.S.
        • Krikun G.
        • Taylor H.S.
        Consider some of the publications of Hugh Taylor: stem cells in endometrium and their role in the pathogenesis of endometriosis.
        Ann N Y Acad Sci. 2011; 1226: 52
        • Taylor H.S.
        • Osteen K.G.
        • Bruner-Tran K.L.
        • et al.
        Novel therapies targeting endometriosis.
        Reprod Sci. 2011; 18: 814-823
        • Vercellini P.
        • Somigliana E.
        • Viganò P.
        • Abbiati A.
        • Barbara G.
        • Crosignani P.G.
        Endometriosis: current therapies and new pharmacological developments.
        Drugs. 2009; 69: 649-675
        • Redwine D.B.
        • Wright J.T.
        Laparoscopic treatment of complete obliteration of the cul-de-sac associated with endometriosis: long-term follow-up of en bloc resection.
        Fertil Steril. 2001; 76: 358-365
        • Seracchioli R.
        • Mabrouk M.
        • Manuzzi L.
        • et al.
        Post-operative use of oral contraceptive pills for prevention of anatomical relapse or symptom-recurrence after conservative surgery for endometriosis.
        Hum Reprod. 2009; 24: 2729-2735
        • Ueki M.
        Histologic study of endometriosis and examination of lymphatic drainage in and from the uterus.
        Am J Obstet Gynecol. 1991; 165: 201-209
        • Barrier B.F.
        Immunology of endometriosis.
        Clin Obstet Gynecol. 2010; 53: 397-402
        • Koninckx P.R.
        • Craessaerts M.
        • Timmerman D.
        • Cornillie F.
        • Kennedy S.
        Anti-TNF-alpha treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial.
        Hum Reprod. 2008; 23: 2017-2023