International Journal of Rheumatic Diseases 2013; 16: 602–603
CORRESPONDENCE
A rare case of reactive arthritis associated with Enterobius vermicularis infection Dear Editor, Infection by different pathogens is associated with the possible onset of reactive arthritis. Pathogens most frequently involved include viruses and bacteria. However, parasites may be also be involved in post-infectious arthritis, although much more rarely than viruses or bacteria.1 We report here a case of a patient who presented with a clinical and laboratory picture of polyarthritis suggestive of rheumatoid arthritis which was subsequently found to be positive for Enterobius vermicularis infection and who recovered completely from polyarthritis after parasite eradication. A 48-year-old Italian woman with no history of arthritis, presented to our outpatient office at the Sapienza University of Rome with symmetrical polyarthritis involving wrists and proximal inter-phalangial joints of the hands. She also complained of the presence of lowgrade fever over the past 7–10 days. The affected joints were swollen, tender and warm. There was no history of a previous genital infection or diarrhea. An X-ray of her wrists and hands showed no evidence of joint space narrowing or bone erosions. Laboratory investigation showed a mild anemia (hemoglobin 10.5 mg/dL), slightly increased white blood cell count (9200/mm3) with significant eosinophilia (16%), increased erythrocyte sedimentation rate (48 mm/h), slightly increased C-reactive protein (CRP: 0.13 mg/L, normal value < 0.1 mg/L), the presence of rheumatoid factor (RF: 55 IU; normal value < 15 IU) and positive antinuclear antibodies (ANA) at high titer (1 : 1280) with a nuclear pattern. Anti-citrullinated protein antibody was also negative as well as extractable nuclear antigens (ENA) and double-stranded anti-DNA antibody. C3 and C4 complement fractions were also within the normal range. Both c- and p-antineutrophil cytoplasmic antibodies (ANCA) were absent. Liver enzymes and all the indices of renal function were within the normal range. Protein electrophoresis showed an increased polyclonal gamma-globulin fraction, with normal albumin. Accurate history-taking revealed the presence of perianal itching since about 6 months. A parasitological stool
test as well as a Scotch tape test were then ordered. Results revealed the presence of E. vermicularis ova identified by both characteristic size and shape on the stool surface and on the tape. Complete parasitological investigation revealed the absence of any other parasite infection. A search for family members with the infection was negative. After about a week from patient presentation, a diagnosis of atypical (RF+ and ANA+) reactive arthritis was then made. The patient was then started on praziquantel and coxib (etoricoxib 90 mg/day for 10 days). After 4 months follow-up, she was completely asymptomatic, without the onset of any new articular symptoms. Parasitic stool test was repeatedly negative for E. vermicularis ova. A control X-ray of her wrists and hands was normal, and laboratory results showed the absence of RF and the disappearance of ANA from serum. Erythrocyte sedimentation rate was also within the normal range and the normalization of eosinophil count was observed. E. vermicularis infection is usually asymptomatic. The most common symptom is pruritus in the perianal region, but infestation may also present with ileocolitis, urinary tract infection, salpingitis and appendicitis.2 The presence of E. vermicularis is also associated with chronic inflammatory intestinal infiltrates and eosinophilia.3 In the case reported here we found that chronic parasitic infection due to E. vermicularis induced a reversibile autoimmune response associated with symmetrical poliarthritis of the small joints of the hands. In a previous study a negative association between schistosome infection and ANA levels was found.4 Many other studies, on the contrary, have described a positive association between parasitic infection and autoimmunity. Lapa et al.5 reported the case of a patient who developed polyarthralgia during schistosoma mansoni infection, with subsequent regression of the disease after anti-parasitic therapy. The mechanisms by which parasites can cause immune damage to host cells may include antigenic mimicry between host and invader, with production of self-reactive pathogenic antibodies, abnormal activation of B-lymphocytes with polyclonal
© 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd
Correspondence
antibodies and acute phase protein production.6 Eosinophils, along with lymphocytes, are the cell types which are prevalent at the site of inflammation to try to clear the parasites by the release of toxic granules and by direct cytotoxicity. There are four reported studies so-far on autoimmune responses to E. vermicularis. The first study examined chronic urticaria and its relationship to enterobiosis.7 In the second article, published in 2000, Drulovic et al.8 reported on a case of antiphospholipid syndrome causing transverse myelopathy with evidence that E. vermicularis infection was the trigger. In fact, cross-reactive antibodies against both nematode antigens and host myelin tissue were found. Further evidence was suggested by the so-called Jarisch– Herxheimer reaction, in which a marked worsening of the clinical state occurred when the enterobiosis was treated with mebendazole, resulting in a subsequent release of fresh parasitic antigen. The third study, reported in 2001, looked at the relationship between allergy and enterobiosis and demonstrated that in an allergic group of children enterobiosis was more prevalent than in a non-allergic group. This is in strict contrast with the hygiene hypothesis.9 The last study describes a case of intra-peritoneal E. vermicularis infection, in which autoimmune signs and symptoms recovered after parisitic eradication.10 In our patient we found that polyarthritis was related to an autoimmune activation as suggested by the appearance of ANA at an high titer and of RF in serum. After 4 months of parasitic elimination, the disappearance of both ANA and RF was associated with clinical recovery, indicating the complete reversibility of the self-reactive immune activation. Immunological investigation indicated that a systemic immune activation actually occurred in the form of an atypical reactive arthritis, and it can be assumed reasonably that this autoimmune response was triggered by E. vermicularis infection. Further study is needed to clarify the immunological mechanisms of possible transient immune reaction during E. vermicularis infection.
Daniele ACCAPEZZATO,1 Marino PAROLI2 and Vincenzo BARNABA1 1
Dipartimento di Medicina Interna e Specialita` Mediche, and 2Dipartimento di Scienze e Biotecnologie MedicoChirurgiche, Sapienza Universita` di Roma, Rome, Italy Correspondence: Dr Daniele Accapezzato, email: [email protected]
REFERENCES 1 Ross AGP, Bartley PB, Sleigh AC et al. (2002) Schistosomiasis. N Engl J Med 346, 1212–20. 2 Arca MJ, Gates RL, Groner JI, Hammond S, Caniano DA (2004) Clinical manifestations of appendicial pinworms in children: an institutional experience and a review of the literature. Pediatr Surg Int 20, 372–5. 3 Surmont I, Liu LX (1995) Enteritis, eosinophilia and enterovirus vermicularis. Lancet 346, 1167. 4 Mutapi F, Imai N, Naushc N et al. (2011) Schistosome infection intensity is inversely related to auto-reactive antibody levels. PLoS ONE 6, e19149. 5 Lapa AT, Appenzeller S, Bertolo MB (2013) Schistosoma mansoni infection: an immune complex disease presenting with polyarthritis. Rheumatol Int 33, 1341–3. 6 Abu-Shakra M, Buskila D, Shoenfeld Y (1999) Molecular mimicry between host and pathogen: examples from parasites and implication. Immunol Lett 67, 147–52. 7 Montag A, Ulrich R (1992) Chronic urticaria in Enterobiasis vermicularis (Oxyuriasis). Hautarzt 43, 652–3. 8 Drulovic J, Dujmovic I, Stojsavlevic N et al. (2000) Transverse myelopathy in the antiphospholipid antibody syndrome: pinworm infestation as a trigger? J Neurol Neurosurg Psychiatry 68, 249. 9 Herrstrom P, Henricson KA, Raberg A et al. (2001) Allergic disease and the infestation of Enterobius vermicularis in Swedish children 4–10 years of age. J Investig Allergol Clin Immunol 11, 157–60. 10 Thomson JC (2004) Pelvic pain caused by intraperitoneal Enterobius vermicularis (threadworm) ova with an associated systemic autoimmune reaction. J Obstet Gynaecol Res 30, 90–5.
CONFLICT OF INTEREST No conflict of interest was declared.
International Journal of Rheumatic Diseases 2013; 16: 602–603
603
CORRESPONDENCE
A rare case of reactive arthritis associated with Enterobius vermicularis infection Dear Editor, Infection by different pathogens is associated with the possible onset of reactive arthritis. Pathogens most frequently involved include viruses and bacteria. However, parasites may be also be involved in post-infectious arthritis, although much more rarely than viruses or bacteria.1 We report here a case of a patient who presented with a clinical and laboratory picture of polyarthritis suggestive of rheumatoid arthritis which was subsequently found to be positive for Enterobius vermicularis infection and who recovered completely from polyarthritis after parasite eradication. A 48-year-old Italian woman with no history of arthritis, presented to our outpatient office at the Sapienza University of Rome with symmetrical polyarthritis involving wrists and proximal inter-phalangial joints of the hands. She also complained of the presence of lowgrade fever over the past 7–10 days. The affected joints were swollen, tender and warm. There was no history of a previous genital infection or diarrhea. An X-ray of her wrists and hands showed no evidence of joint space narrowing or bone erosions. Laboratory investigation showed a mild anemia (hemoglobin 10.5 mg/dL), slightly increased white blood cell count (9200/mm3) with significant eosinophilia (16%), increased erythrocyte sedimentation rate (48 mm/h), slightly increased C-reactive protein (CRP: 0.13 mg/L, normal value < 0.1 mg/L), the presence of rheumatoid factor (RF: 55 IU; normal value < 15 IU) and positive antinuclear antibodies (ANA) at high titer (1 : 1280) with a nuclear pattern. Anti-citrullinated protein antibody was also negative as well as extractable nuclear antigens (ENA) and double-stranded anti-DNA antibody. C3 and C4 complement fractions were also within the normal range. Both c- and p-antineutrophil cytoplasmic antibodies (ANCA) were absent. Liver enzymes and all the indices of renal function were within the normal range. Protein electrophoresis showed an increased polyclonal gamma-globulin fraction, with normal albumin. Accurate history-taking revealed the presence of perianal itching since about 6 months. A parasitological stool
test as well as a Scotch tape test were then ordered. Results revealed the presence of E. vermicularis ova identified by both characteristic size and shape on the stool surface and on the tape. Complete parasitological investigation revealed the absence of any other parasite infection. A search for family members with the infection was negative. After about a week from patient presentation, a diagnosis of atypical (RF+ and ANA+) reactive arthritis was then made. The patient was then started on praziquantel and coxib (etoricoxib 90 mg/day for 10 days). After 4 months follow-up, she was completely asymptomatic, without the onset of any new articular symptoms. Parasitic stool test was repeatedly negative for E. vermicularis ova. A control X-ray of her wrists and hands was normal, and laboratory results showed the absence of RF and the disappearance of ANA from serum. Erythrocyte sedimentation rate was also within the normal range and the normalization of eosinophil count was observed. E. vermicularis infection is usually asymptomatic. The most common symptom is pruritus in the perianal region, but infestation may also present with ileocolitis, urinary tract infection, salpingitis and appendicitis.2 The presence of E. vermicularis is also associated with chronic inflammatory intestinal infiltrates and eosinophilia.3 In the case reported here we found that chronic parasitic infection due to E. vermicularis induced a reversibile autoimmune response associated with symmetrical poliarthritis of the small joints of the hands. In a previous study a negative association between schistosome infection and ANA levels was found.4 Many other studies, on the contrary, have described a positive association between parasitic infection and autoimmunity. Lapa et al.5 reported the case of a patient who developed polyarthralgia during schistosoma mansoni infection, with subsequent regression of the disease after anti-parasitic therapy. The mechanisms by which parasites can cause immune damage to host cells may include antigenic mimicry between host and invader, with production of self-reactive pathogenic antibodies, abnormal activation of B-lymphocytes with polyclonal
© 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd
Correspondence
antibodies and acute phase protein production.6 Eosinophils, along with lymphocytes, are the cell types which are prevalent at the site of inflammation to try to clear the parasites by the release of toxic granules and by direct cytotoxicity. There are four reported studies so-far on autoimmune responses to E. vermicularis. The first study examined chronic urticaria and its relationship to enterobiosis.7 In the second article, published in 2000, Drulovic et al.8 reported on a case of antiphospholipid syndrome causing transverse myelopathy with evidence that E. vermicularis infection was the trigger. In fact, cross-reactive antibodies against both nematode antigens and host myelin tissue were found. Further evidence was suggested by the so-called Jarisch– Herxheimer reaction, in which a marked worsening of the clinical state occurred when the enterobiosis was treated with mebendazole, resulting in a subsequent release of fresh parasitic antigen. The third study, reported in 2001, looked at the relationship between allergy and enterobiosis and demonstrated that in an allergic group of children enterobiosis was more prevalent than in a non-allergic group. This is in strict contrast with the hygiene hypothesis.9 The last study describes a case of intra-peritoneal E. vermicularis infection, in which autoimmune signs and symptoms recovered after parisitic eradication.10 In our patient we found that polyarthritis was related to an autoimmune activation as suggested by the appearance of ANA at an high titer and of RF in serum. After 4 months of parasitic elimination, the disappearance of both ANA and RF was associated with clinical recovery, indicating the complete reversibility of the self-reactive immune activation. Immunological investigation indicated that a systemic immune activation actually occurred in the form of an atypical reactive arthritis, and it can be assumed reasonably that this autoimmune response was triggered by E. vermicularis infection. Further study is needed to clarify the immunological mechanisms of possible transient immune reaction during E. vermicularis infection.
Daniele ACCAPEZZATO,1 Marino PAROLI2 and Vincenzo BARNABA1 1
Dipartimento di Medicina Interna e Specialita` Mediche, and 2Dipartimento di Scienze e Biotecnologie MedicoChirurgiche, Sapienza Universita` di Roma, Rome, Italy Correspondence: Dr Daniele Accapezzato, email: [email protected]
REFERENCES 1 Ross AGP, Bartley PB, Sleigh AC et al. (2002) Schistosomiasis. N Engl J Med 346, 1212–20. 2 Arca MJ, Gates RL, Groner JI, Hammond S, Caniano DA (2004) Clinical manifestations of appendicial pinworms in children: an institutional experience and a review of the literature. Pediatr Surg Int 20, 372–5. 3 Surmont I, Liu LX (1995) Enteritis, eosinophilia and enterovirus vermicularis. Lancet 346, 1167. 4 Mutapi F, Imai N, Naushc N et al. (2011) Schistosome infection intensity is inversely related to auto-reactive antibody levels. PLoS ONE 6, e19149. 5 Lapa AT, Appenzeller S, Bertolo MB (2013) Schistosoma mansoni infection: an immune complex disease presenting with polyarthritis. Rheumatol Int 33, 1341–3. 6 Abu-Shakra M, Buskila D, Shoenfeld Y (1999) Molecular mimicry between host and pathogen: examples from parasites and implication. Immunol Lett 67, 147–52. 7 Montag A, Ulrich R (1992) Chronic urticaria in Enterobiasis vermicularis (Oxyuriasis). Hautarzt 43, 652–3. 8 Drulovic J, Dujmovic I, Stojsavlevic N et al. (2000) Transverse myelopathy in the antiphospholipid antibody syndrome: pinworm infestation as a trigger? J Neurol Neurosurg Psychiatry 68, 249. 9 Herrstrom P, Henricson KA, Raberg A et al. (2001) Allergic disease and the infestation of Enterobius vermicularis in Swedish children 4–10 years of age. J Investig Allergol Clin Immunol 11, 157–60. 10 Thomson JC (2004) Pelvic pain caused by intraperitoneal Enterobius vermicularis (threadworm) ova with an associated systemic autoimmune reaction. J Obstet Gynaecol Res 30, 90–5.
CONFLICT OF INTEREST No conflict of interest was declared.
International Journal of Rheumatic Diseases 2013; 16: 602–603
603
