http://informahealthcare.com/mor ISSN 1439-7595 (print), 1439-7609 (online) Mod Rheumatol, 2013; Early Online: 1–3 © 2013 Japan College of Rheumatology DOI: 10.3109/14397595.2013.844388
CASE REPORT
Successful treatment of Group A b-hemolytic Streptococcus infection-associated juvenile cutaneous polyarteritis nodosa with tonsillectomy
Mod Rheumatol Downloaded from informahealthcare.com by Nyu Medical Center on 05/31/15 For personal use only.
Takeshi Yamamoto1, Yuzaburo Inoue1, Minako Tomiita2, Makiko Oikawa3,4, Naotomo Kambe3, Takayasu Arima1, Naoki Shimojo1, and Yoichi Kohno1 1Department of Pediatrics, Graduate School of Medicine, Chiba University, Chuou-ku, Chiba City, Chiba, Japan, 2Department of Allergy and
Rheumatology, Chiba Children’s Hospital, Midori-ku, Chiba City, Chiba, Japan, 3Department of Dermatology, Chiba University Graduate School of Medicine, Chuou-ku, Chiba City, Chiba, Japan, and 4Department of Dermatology, Chiba Aoba Municipal Hospital, Chuo-ku, Chiba, Japan Abstract Cutaneous polyarteritis nodosa (cutaneous PAN) is a form of necrotizing vasculitis of small- and medium-sized arteries, primarily involving the skin. In juvenile cases, cutaneous PAN is known to be frequently associated with Group A β-hemolytic Streptococcus (GAS) infections. We herein describe the first reported juvenile case of GAS-associated recurrent cutaneous PAN successfully improved with tonsillectomy. To avoid the use of steroids and immunosuppressive drugs, especially in juvenile cases, tonsillectomy is a possible treatment for GAS-associated recurrent cutaneous PAN.
Introduction Cutaneous polyarteritis nodosa (cutaneous PAN) is a form of necrotizing vasculitis of small- and medium-sized arteries, primarily involving the skin [1]. The histological features of the skin lesions are similar to those of systemic polyarteritis nodosa (systemic PAN). However, cutaneous PAN is characterized by the absence of major organ involvement and is therefore recognized to be a separate entity from systemic PAN [2]. Compared to systemic PAN, cutaneous PAN is known to be more frequently associated with infections, especially in juvenile cases [3,4]. The most commonly identified pathogen in juvenile cutaneous PAN cases is Group A β-hemolytic Streptococcus (GAS) [5,6]. In fact, it has been reported that approximately 80% of juvenile patients develop or suffer from exacerbation of cutaneous PAN following GAS infections [7]. However, due to the limited efficacy of antibiotic prophylaxis for GAS, approximately 30% of patients with cutaneous PAN suffer from continuous or recurrent symptoms and require the use of steroids and/or immunosuppressive drugs [7], which should be avoided in children whenever possible. In this report, we describe the first reported juvenile case of GAS-associated recurrent cutaneous PAN successfully improved with tonsillectomy. The patient’s cutaneous PAN was not controlled with antibiotic prophylaxis and low-dose methotrexate (MTX) for 3 years. However, since the tonsillectomy, the cutaneous PAN has not relapsed for over 2 years; thus, we have not
Correspondence to: Yuzaburo Inoue, MD, PhD, Department of Pediatrics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba 260-8670, Japan. Tel: ⫹ 81-43-226-2144. Fax: ⫹ 81-43226-2145. E-mail: [email protected]
Keywords Cutaneous polyarteritis nodosa, Group A β-hemolytic Streptococcus, Tonsillectomy History Received 25 February 2013 Accepted 30 August 2013 Published online 18 October 2013
needed to add steroids or other immunosuppressive drugs to the patient’s therapy. We believe that tonsillectomy is a possible treatment for cutaneous PAN, especially in juvenile cases.
Case report A previously healthy 4-year-old girl was admitted to our hospital with a persistent fever after her sister suffered from GAS tonsillitis 2 weeks prior to the admission. The patient’s symptoms included a fever of over 38°C and multiple tender erythematous nodules ranging from 1 to 20 mm in diameter on the extremities (Figure 1a) without any major organ involvement, such as myalgia or muscle tenderness, hypertension, peripheral neuropathy or renal involvement. Blood examinations revealed the following findings: white blood cells: 36.7 ⫻ 103/μl; platelet count: 78.8 ⫻ 103/μl; erythrocyte sedimentation rate: 127 mm/h; and C-reactive protein (CRP): 12 mg/dl. The serum immunoglobulin levels were elevated: IgG: 3,238 mg/dl; IgA: 426 mg/dl; and IgM: 137 mg/dl. The levels of total hemolytic complement (CH50) and C3 were also high at 68.9 U/ml and 182 mg/dl, respectively. The levels of thrombin– antithrombin complex (32.2 ng/ml) and D-dimer (8.0 mg/dl) were elevated, while other test results of blood coagulation and fibrinolysis were normal. The level of lupus anticoagulant was not evaluated. The findings of blood chemistry, blood cultures, urine cultures, X-ray, electrocardiogram and echocardiogram were unremarkable. The results of laboratory tests for rheumatic diseases, including rheumatoid factor, antinuclear antibodies, antineutrophil cytoplasmic antibodies, anti-β2-glycoprotein I-dependent cardiolipin antibodies and anti-phosphatidylserine/prothrombin antibodies, were negative. Serology for hepatitis B and C, cytomegalovirus, Epstein– Barr virus, Bartonella henselae and Orientia tsutsugamushi was negative. A tuberculin test was negative and examinations of the patient’s bone marrow showed no abnormalities.
2
T. Yamamoto et al.
Mod Rheumatol, 2013; Early Online: 1–3
Mod Rheumatol Downloaded from informahealthcare.com by Nyu Medical Center on 05/31/15 For personal use only.
Figure 1. (a) Erythematous nodules on the dorsum of the hands measuring 10 mm or less. (b) Histopathological features of the skin biopsy. Necrotizing vasculitis with fibrinoid degeneration was observed in the underlying dermal medium-sized arteries (hematoxylin–eosin stain; original magnification ⫻10). (c) A magnified view of the arteritis showing degeneration of the arterial wall with deposition of fibrinoid material and mild perivascular inflammatory infiltrates (hematoxylin– eosin stain; original magnification ⫻400). (d) The clinical course of the patient. Elevation of the CRP level together with the clinical symptoms of cutaneous PAN (fever, multiple tender erythematous nodules, etc.) is marked with black arrows.
We performed a skin biopsy of the area of erythema of the right dorsalis pedis. Necrotizing vasculitis of the mediumsized arteries under the dermis with fibrinoid degeneration was observed (Figure 1b, c), which is a specific pathological finding of polyarteritis nodosa. As the patient’s sister had suffered from GAS tonsillitis just before the patient developed a fever, we conducted GAS infection-related tests. Although we did not find GAS in a throat culture, both the anti-streptolysin O antibody (ASO) titer (366 U/ml) and the anti-streptokinase antibody (ASK) titer (1:40,960) were extremely high, which suggested that the patient had a GAS infection. Although fever is an exclusion manifestation in the diagnostic criteria of cutaneous PAN defined in adult cases only [2], it has been reported that approximately 40% of juvenile patients with cutaneous PAN had a fever in a multicenter survey [3]. In addition, the current patient did not exhibit any major organ involvement suggestive of systemic PAN, such as hypertension or renal involvement. Therefore, we diagnosed the patient’s illness as cutaneous PAN associated with a GAS infection. We initially treated the patient with ibuprofen and dipyridamole due to concerns about side effects of steroids in children. Fortunately, her symptoms promptly disappeared, and she was discharged from the hospital 1 month later. After discharge, we continued to administer ibuprofen and dipyridamole and initiated treatment with penicillin prophylaxis to prevent relapse of cutaneous PAN triggered by the GAS infection in reference to the use of penicillin prophylaxis for rheumatic fever. However, in spite of not having any apparent GAS infections, the patient occasionally exhibited a fever and multiple tender erythematous nodules accompanied by elevation of the CRP level without any apparent infection (Figure 1d). Therefore, to control the patient’s disease condition, low-dose oral MTX therapy (4.5 mg/m2 (body surface area)/week) was initiated after the third relapse (Figure 1d). After initiating this therapy, the patient’s relapsing symptoms disappeared, although elevation of the CRP level (5–10 mg/dl) was observed approximately twice a year. At 7 years of age, the patient suffered from GAS tonsillitis under penicillin prophylaxis. Two weeks after the GAS infection, the cutaneous PAN relapsed, and the use of systemic steroids (prednisolone 2 mg/kg) was required. Although the patient did not exhibit apparent GAS tonsillitis with every relapse of cutaneous PAN, the last relapse of cutaneous PAN strongly indicated that GAS infection was a trigger of the cutaneous PAN. We thus
decided to perform tonsillectomy for the purpose of controlling the GAS-associated cutaneous PAN. Surprisingly, after the tonsillectomy, no symptoms of cutaneous PAN or episodes of elevation of the CRP level occurred for more than 2 years. In addition, the ASO titer, the ASK titer, the serum immunoglobulin levels and the complement titers gradually decreased to normal. Ibuprofen was tapered after the tonsillectomy and discontinued when the patient was 9 years of age. MTX was tapered gradually to two-thirds of the original dose at 10 years of age. We plan to complete the regimen of MTX.
Discussion Our case is the first reported juvenile case of GAS-associated recurrent cutaneous PAN successfully improved with tonsillectomy. To our knowledge, there are only two reported cases of cutaneous PAN improved with tonsillectomy [8]. In addition, all of these cases involved adults, not children. The two adult patients with cutaneous PAN were able to tolerate withdraw of treatment with steroids without exacerbation of the disease, and both patients have been free from disease for 1 year and 8 months, suggesting that their cutaneous PAN was cured by tonsillectomy. As these two adult patients suffered from tonsillitis before developing cutaneous PAN, tonsillectomy may be a curative treatment for cutaneous PAN accompanied by tonsillitis. Because juvenile cutaneous PAN is known to be more frequently associated with infections, such as GAS, than adult cutaneous PAN, we believe that tonsillectomy should be considered a choice of treatment for GAS-associated recurrent cutaneous PAN to avoid the use of steroids and immunosuppressive drugs and aim to cure cutaneous PAN, especially in juvenile cases. In our case, tonsillectomy successfully improved not only the control of GAS-associated cutaneous PAN, but also the markers of sustained inflammation, such as high levels of complements and immunoglobulins. These observations suggest that the tonsils were the pathogenic organ for our patient’s cutaneous PAN in which immune responses to GAS occurred. Similarly, it has been shown that tonsillectomy can improve several immunological disorders, including IgA nephropathy [9], psoriasis [10] and Henoch–Schönlein purpura nephritis [11]. In patients with IgA nephropathy, tonsillectomy can eliminate IgA originating from the tonsils, which decreases the level of IgA immunocomplex in the circulation. In patients with psoriasis, tonsillectomy has been
DOI 10.3109/14397595.2013.844388
Tonsillectomy for juvenile cutaneous polyarteritis nodosa 3
reported to decrease the level of pathogenic skin-homing T-cells in the circulation. Therefore, immunoglobulins and T-cells originating from the tonsils could be pathogenic for cutaneous PAN in our case. Another possible immunological mechanism by which tonsillectomy improves cutaneous PAN is microthrombopathy due to GAS-induced antiphospholipid antibodies produced in the tonsils [12]. However, we have not detected any antiphospholipid antibodies in this case thus far. Further studies are needed to address this issue.
its definition and diagnostic criteria. Arch Dermatol Res. 2009; 301(1):117–21. Ozen S, Anton J, Arisoy N, Bakkaloglu A, Besbas N, Brogan P, et al. Juvenile polyarteritis: results of a multicenter survey of 110 children. J Pediatr. 2004;145(4):517–22. Fathalla BM, Miller L, Brady S, Schaller JG. Cutaneous polyarteritis nodosa in children. J Am Acad Dermatol. 2005;53(4):724–8. Albornoz MA, Benedetto AV, Korman M, McFall S, Tourtellotte CD, Myers AR. Relapsing cutaneous polyarteritis nodosa associated with streptococcal infections. Int J Dermatol. 1998;37(9):664–6. David J, Ansell BM, Woo P. Polyarteritis nodosa associated with streptococcus. Arch Dis Child. 1993;69(6):685–8. Bansal NK, Houghton KM. Cutaneous polyarteritis nodosa in childhood: a case report and review of the literature. Arthritis. 2010;2010:687547. Misago N, Mochizuki Y, Sekiyama-Kodera H, Shirotani M, Suzuki K, Inokuchi A, Narisawa Y. Cutaneous polyarteritis nodosa: therapy and clinical course in four cases. J Dermatol. 2001;28(12):719–27. Komatsu H, Fujimoto S. Tonsillectomy combined with steroid pulse therapy induces clinical remission of IgA nephropathy. Adv Otorhinolaryngol 2011;72:57–9. Thorleifsdottir RH, Sigurdardottir SL, Sigurgeirsson B, Olafsson JH, Sigurdsson MI, Petersen H, et al. Improvement of psoriasis after tonsillectomy is associated with a decrease in the frequency of circulating T cells that recognize streptococcal determinants and homologous skin determinants. J Immunol 2012;188(10):5160–5. Iwazu Y, Akimoto T, Muto S, Kusano E. Clinical remission of Henoch-Schonlein purpura nephritis after a monotherapeutic tonsillectomy. Clin Exp Nephrol 2011;15(1):132–5. Kawakami T, Yamazaki M, Mizoguchi M, Soma Y. High titer of anti-phosphatidylserine-prothrombin complex antibodies in patients with cutaneous polyarteritis nodosa. Arthritis Rheum. 2007; 57(8):1507–13.
Mod Rheumatol Downloaded from informahealthcare.com by Nyu Medical Center on 05/31/15 For personal use only.
Acknowledgements We are grateful to Dr. Tetsuya Horita and Dr. Tatsuya Atsumi, Department of Medicine Π, Hokkaido University Graduate School of Medicine, for measuring anti-phosphatidylserine/ prothrombin antibodies; to Dr. Daiju Sakurai and other members of Otolaryngology, Graduate School of Medicine, Chiba University, for performing a tonsillectomy; to Dr. Brian Quinn for reviewing the manuscript.
3. 4. 5. 6. 7. 8. 9. 10.
Conflict of interest None. 11.
References 1. Morgan AJ, Schwartz RA. Cutaneous polyarteritis nodosa: a comprehensive review. Int J Dermatol. 2010;49(7):750–6. 2. Nakamura T, Kanazawa N, Ikeda T, Yamamoto Y, Nakabayashi K, Ozaki S, Furukawa F. Cutaneous polyarteritis nodosa: revisiting
12.
CASE REPORT
Successful treatment of Group A b-hemolytic Streptococcus infection-associated juvenile cutaneous polyarteritis nodosa with tonsillectomy
Mod Rheumatol Downloaded from informahealthcare.com by Nyu Medical Center on 05/31/15 For personal use only.
Takeshi Yamamoto1, Yuzaburo Inoue1, Minako Tomiita2, Makiko Oikawa3,4, Naotomo Kambe3, Takayasu Arima1, Naoki Shimojo1, and Yoichi Kohno1 1Department of Pediatrics, Graduate School of Medicine, Chiba University, Chuou-ku, Chiba City, Chiba, Japan, 2Department of Allergy and
Rheumatology, Chiba Children’s Hospital, Midori-ku, Chiba City, Chiba, Japan, 3Department of Dermatology, Chiba University Graduate School of Medicine, Chuou-ku, Chiba City, Chiba, Japan, and 4Department of Dermatology, Chiba Aoba Municipal Hospital, Chuo-ku, Chiba, Japan Abstract Cutaneous polyarteritis nodosa (cutaneous PAN) is a form of necrotizing vasculitis of small- and medium-sized arteries, primarily involving the skin. In juvenile cases, cutaneous PAN is known to be frequently associated with Group A β-hemolytic Streptococcus (GAS) infections. We herein describe the first reported juvenile case of GAS-associated recurrent cutaneous PAN successfully improved with tonsillectomy. To avoid the use of steroids and immunosuppressive drugs, especially in juvenile cases, tonsillectomy is a possible treatment for GAS-associated recurrent cutaneous PAN.
Introduction Cutaneous polyarteritis nodosa (cutaneous PAN) is a form of necrotizing vasculitis of small- and medium-sized arteries, primarily involving the skin [1]. The histological features of the skin lesions are similar to those of systemic polyarteritis nodosa (systemic PAN). However, cutaneous PAN is characterized by the absence of major organ involvement and is therefore recognized to be a separate entity from systemic PAN [2]. Compared to systemic PAN, cutaneous PAN is known to be more frequently associated with infections, especially in juvenile cases [3,4]. The most commonly identified pathogen in juvenile cutaneous PAN cases is Group A β-hemolytic Streptococcus (GAS) [5,6]. In fact, it has been reported that approximately 80% of juvenile patients develop or suffer from exacerbation of cutaneous PAN following GAS infections [7]. However, due to the limited efficacy of antibiotic prophylaxis for GAS, approximately 30% of patients with cutaneous PAN suffer from continuous or recurrent symptoms and require the use of steroids and/or immunosuppressive drugs [7], which should be avoided in children whenever possible. In this report, we describe the first reported juvenile case of GAS-associated recurrent cutaneous PAN successfully improved with tonsillectomy. The patient’s cutaneous PAN was not controlled with antibiotic prophylaxis and low-dose methotrexate (MTX) for 3 years. However, since the tonsillectomy, the cutaneous PAN has not relapsed for over 2 years; thus, we have not
Correspondence to: Yuzaburo Inoue, MD, PhD, Department of Pediatrics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba 260-8670, Japan. Tel: ⫹ 81-43-226-2144. Fax: ⫹ 81-43226-2145. E-mail: [email protected]
Keywords Cutaneous polyarteritis nodosa, Group A β-hemolytic Streptococcus, Tonsillectomy History Received 25 February 2013 Accepted 30 August 2013 Published online 18 October 2013
needed to add steroids or other immunosuppressive drugs to the patient’s therapy. We believe that tonsillectomy is a possible treatment for cutaneous PAN, especially in juvenile cases.
Case report A previously healthy 4-year-old girl was admitted to our hospital with a persistent fever after her sister suffered from GAS tonsillitis 2 weeks prior to the admission. The patient’s symptoms included a fever of over 38°C and multiple tender erythematous nodules ranging from 1 to 20 mm in diameter on the extremities (Figure 1a) without any major organ involvement, such as myalgia or muscle tenderness, hypertension, peripheral neuropathy or renal involvement. Blood examinations revealed the following findings: white blood cells: 36.7 ⫻ 103/μl; platelet count: 78.8 ⫻ 103/μl; erythrocyte sedimentation rate: 127 mm/h; and C-reactive protein (CRP): 12 mg/dl. The serum immunoglobulin levels were elevated: IgG: 3,238 mg/dl; IgA: 426 mg/dl; and IgM: 137 mg/dl. The levels of total hemolytic complement (CH50) and C3 were also high at 68.9 U/ml and 182 mg/dl, respectively. The levels of thrombin– antithrombin complex (32.2 ng/ml) and D-dimer (8.0 mg/dl) were elevated, while other test results of blood coagulation and fibrinolysis were normal. The level of lupus anticoagulant was not evaluated. The findings of blood chemistry, blood cultures, urine cultures, X-ray, electrocardiogram and echocardiogram were unremarkable. The results of laboratory tests for rheumatic diseases, including rheumatoid factor, antinuclear antibodies, antineutrophil cytoplasmic antibodies, anti-β2-glycoprotein I-dependent cardiolipin antibodies and anti-phosphatidylserine/prothrombin antibodies, were negative. Serology for hepatitis B and C, cytomegalovirus, Epstein– Barr virus, Bartonella henselae and Orientia tsutsugamushi was negative. A tuberculin test was negative and examinations of the patient’s bone marrow showed no abnormalities.
2
T. Yamamoto et al.
Mod Rheumatol, 2013; Early Online: 1–3
Mod Rheumatol Downloaded from informahealthcare.com by Nyu Medical Center on 05/31/15 For personal use only.
Figure 1. (a) Erythematous nodules on the dorsum of the hands measuring 10 mm or less. (b) Histopathological features of the skin biopsy. Necrotizing vasculitis with fibrinoid degeneration was observed in the underlying dermal medium-sized arteries (hematoxylin–eosin stain; original magnification ⫻10). (c) A magnified view of the arteritis showing degeneration of the arterial wall with deposition of fibrinoid material and mild perivascular inflammatory infiltrates (hematoxylin– eosin stain; original magnification ⫻400). (d) The clinical course of the patient. Elevation of the CRP level together with the clinical symptoms of cutaneous PAN (fever, multiple tender erythematous nodules, etc.) is marked with black arrows.
We performed a skin biopsy of the area of erythema of the right dorsalis pedis. Necrotizing vasculitis of the mediumsized arteries under the dermis with fibrinoid degeneration was observed (Figure 1b, c), which is a specific pathological finding of polyarteritis nodosa. As the patient’s sister had suffered from GAS tonsillitis just before the patient developed a fever, we conducted GAS infection-related tests. Although we did not find GAS in a throat culture, both the anti-streptolysin O antibody (ASO) titer (366 U/ml) and the anti-streptokinase antibody (ASK) titer (1:40,960) were extremely high, which suggested that the patient had a GAS infection. Although fever is an exclusion manifestation in the diagnostic criteria of cutaneous PAN defined in adult cases only [2], it has been reported that approximately 40% of juvenile patients with cutaneous PAN had a fever in a multicenter survey [3]. In addition, the current patient did not exhibit any major organ involvement suggestive of systemic PAN, such as hypertension or renal involvement. Therefore, we diagnosed the patient’s illness as cutaneous PAN associated with a GAS infection. We initially treated the patient with ibuprofen and dipyridamole due to concerns about side effects of steroids in children. Fortunately, her symptoms promptly disappeared, and she was discharged from the hospital 1 month later. After discharge, we continued to administer ibuprofen and dipyridamole and initiated treatment with penicillin prophylaxis to prevent relapse of cutaneous PAN triggered by the GAS infection in reference to the use of penicillin prophylaxis for rheumatic fever. However, in spite of not having any apparent GAS infections, the patient occasionally exhibited a fever and multiple tender erythematous nodules accompanied by elevation of the CRP level without any apparent infection (Figure 1d). Therefore, to control the patient’s disease condition, low-dose oral MTX therapy (4.5 mg/m2 (body surface area)/week) was initiated after the third relapse (Figure 1d). After initiating this therapy, the patient’s relapsing symptoms disappeared, although elevation of the CRP level (5–10 mg/dl) was observed approximately twice a year. At 7 years of age, the patient suffered from GAS tonsillitis under penicillin prophylaxis. Two weeks after the GAS infection, the cutaneous PAN relapsed, and the use of systemic steroids (prednisolone 2 mg/kg) was required. Although the patient did not exhibit apparent GAS tonsillitis with every relapse of cutaneous PAN, the last relapse of cutaneous PAN strongly indicated that GAS infection was a trigger of the cutaneous PAN. We thus
decided to perform tonsillectomy for the purpose of controlling the GAS-associated cutaneous PAN. Surprisingly, after the tonsillectomy, no symptoms of cutaneous PAN or episodes of elevation of the CRP level occurred for more than 2 years. In addition, the ASO titer, the ASK titer, the serum immunoglobulin levels and the complement titers gradually decreased to normal. Ibuprofen was tapered after the tonsillectomy and discontinued when the patient was 9 years of age. MTX was tapered gradually to two-thirds of the original dose at 10 years of age. We plan to complete the regimen of MTX.
Discussion Our case is the first reported juvenile case of GAS-associated recurrent cutaneous PAN successfully improved with tonsillectomy. To our knowledge, there are only two reported cases of cutaneous PAN improved with tonsillectomy [8]. In addition, all of these cases involved adults, not children. The two adult patients with cutaneous PAN were able to tolerate withdraw of treatment with steroids without exacerbation of the disease, and both patients have been free from disease for 1 year and 8 months, suggesting that their cutaneous PAN was cured by tonsillectomy. As these two adult patients suffered from tonsillitis before developing cutaneous PAN, tonsillectomy may be a curative treatment for cutaneous PAN accompanied by tonsillitis. Because juvenile cutaneous PAN is known to be more frequently associated with infections, such as GAS, than adult cutaneous PAN, we believe that tonsillectomy should be considered a choice of treatment for GAS-associated recurrent cutaneous PAN to avoid the use of steroids and immunosuppressive drugs and aim to cure cutaneous PAN, especially in juvenile cases. In our case, tonsillectomy successfully improved not only the control of GAS-associated cutaneous PAN, but also the markers of sustained inflammation, such as high levels of complements and immunoglobulins. These observations suggest that the tonsils were the pathogenic organ for our patient’s cutaneous PAN in which immune responses to GAS occurred. Similarly, it has been shown that tonsillectomy can improve several immunological disorders, including IgA nephropathy [9], psoriasis [10] and Henoch–Schönlein purpura nephritis [11]. In patients with IgA nephropathy, tonsillectomy can eliminate IgA originating from the tonsils, which decreases the level of IgA immunocomplex in the circulation. In patients with psoriasis, tonsillectomy has been
DOI 10.3109/14397595.2013.844388
Tonsillectomy for juvenile cutaneous polyarteritis nodosa 3
reported to decrease the level of pathogenic skin-homing T-cells in the circulation. Therefore, immunoglobulins and T-cells originating from the tonsils could be pathogenic for cutaneous PAN in our case. Another possible immunological mechanism by which tonsillectomy improves cutaneous PAN is microthrombopathy due to GAS-induced antiphospholipid antibodies produced in the tonsils [12]. However, we have not detected any antiphospholipid antibodies in this case thus far. Further studies are needed to address this issue.
its definition and diagnostic criteria. Arch Dermatol Res. 2009; 301(1):117–21. Ozen S, Anton J, Arisoy N, Bakkaloglu A, Besbas N, Brogan P, et al. Juvenile polyarteritis: results of a multicenter survey of 110 children. J Pediatr. 2004;145(4):517–22. Fathalla BM, Miller L, Brady S, Schaller JG. Cutaneous polyarteritis nodosa in children. J Am Acad Dermatol. 2005;53(4):724–8. Albornoz MA, Benedetto AV, Korman M, McFall S, Tourtellotte CD, Myers AR. Relapsing cutaneous polyarteritis nodosa associated with streptococcal infections. Int J Dermatol. 1998;37(9):664–6. David J, Ansell BM, Woo P. Polyarteritis nodosa associated with streptococcus. Arch Dis Child. 1993;69(6):685–8. Bansal NK, Houghton KM. Cutaneous polyarteritis nodosa in childhood: a case report and review of the literature. Arthritis. 2010;2010:687547. Misago N, Mochizuki Y, Sekiyama-Kodera H, Shirotani M, Suzuki K, Inokuchi A, Narisawa Y. Cutaneous polyarteritis nodosa: therapy and clinical course in four cases. J Dermatol. 2001;28(12):719–27. Komatsu H, Fujimoto S. Tonsillectomy combined with steroid pulse therapy induces clinical remission of IgA nephropathy. Adv Otorhinolaryngol 2011;72:57–9. Thorleifsdottir RH, Sigurdardottir SL, Sigurgeirsson B, Olafsson JH, Sigurdsson MI, Petersen H, et al. Improvement of psoriasis after tonsillectomy is associated with a decrease in the frequency of circulating T cells that recognize streptococcal determinants and homologous skin determinants. J Immunol 2012;188(10):5160–5. Iwazu Y, Akimoto T, Muto S, Kusano E. Clinical remission of Henoch-Schonlein purpura nephritis after a monotherapeutic tonsillectomy. Clin Exp Nephrol 2011;15(1):132–5. Kawakami T, Yamazaki M, Mizoguchi M, Soma Y. High titer of anti-phosphatidylserine-prothrombin complex antibodies in patients with cutaneous polyarteritis nodosa. Arthritis Rheum. 2007; 57(8):1507–13.
Mod Rheumatol Downloaded from informahealthcare.com by Nyu Medical Center on 05/31/15 For personal use only.
Acknowledgements We are grateful to Dr. Tetsuya Horita and Dr. Tatsuya Atsumi, Department of Medicine Π, Hokkaido University Graduate School of Medicine, for measuring anti-phosphatidylserine/ prothrombin antibodies; to Dr. Daiju Sakurai and other members of Otolaryngology, Graduate School of Medicine, Chiba University, for performing a tonsillectomy; to Dr. Brian Quinn for reviewing the manuscript.
3. 4. 5. 6. 7. 8. 9. 10.
Conflict of interest None. 11.
References 1. Morgan AJ, Schwartz RA. Cutaneous polyarteritis nodosa: a comprehensive review. Int J Dermatol. 2010;49(7):750–6. 2. Nakamura T, Kanazawa N, Ikeda T, Yamamoto Y, Nakabayashi K, Ozaki S, Furukawa F. Cutaneous polyarteritis nodosa: revisiting
12.
