- Email: [email protected]
The comparison of phonophoresis, iontophoresis and local steroid injection in carpal tunnel syndrome treatment
Letters to the editor / Joint Bone Spine 76 (2009) 718–725
We concluded to infliximab induced skin and pulmonary sarcoidosis in a RA patient. Infliximab was discontinued in November 2007. Skin lesions have disappeared within 4 months, pulmonary lesions are regressing. In May 2008, rituximab treatment was initiated because of a new flare of RA (DAS28 = 7.26). TNF␣ plays a key role in the pathogenesis of RA [1] and sarcoidosis [2]. TNF␣ and IL-1 are released by alveolar macrophages in sarcoidosis with active lung involvement [3]. Anti-TNF␣ monoclonal antibodies have been used successfully for the treatment of refractory sarcoidosis with or without lung involvement [4]. 2. Discussion We describe the first case of infliximab induced skin and pulmonary sarcoidosis in a RA patient. Almost all case reports of anti-TNF␣ induced sarcoidosis are due to etanercept [5,6] which is known to induce granulomatous diseases such as Crohn disease [7]. These discrepancies observed between monoclonal antibodies and soluble receptors are potentially linked to their differences in term of mechanism of action. In this regard, anti-TNF␣ monoclonal antibodies have been shown to induce more tuberculosis than etanercept [8]. Emergence of a granulomatous disease with infliximab is surprising since these molecules are effective on diseases associated to granulomatous lesions [3]. Only two case reports of sarcoidosis induced by infliximab have been found in literature, none with skin involvement [9,10]. The disappearance of lesions after discontinuation of infliximab is a strong argument for the diagnosis of drug-induced sarcoidosis. Reintroduction of a TNF␣ blocking agent seems unreasonable. In this context, rituximab was introduced for the management of the active RA of our patient. References [1] Matsuno H, Yudoh K, Katayama R, et al. The role of TNF-alpha in the pathogenesis of inflammation and joint destruction in rheumatoid arthritis (RA): a study using a human RA/SCID mouse chimera. Rheumatology (Oxford) 2002;41:329–37. [2] Sweiss NJ, Curran J, Baughman RP. Sarcoidosis, role of tumor necrosis factor inhibitors and other biologic agents, past, present, and future concepts. Clin Dermatol 2007;25:341–6. [3] Todisco T, Vecchiarelli A, Dottorini M, et al. Sarcoidosis: an alveolar macrophage disease? Sarcoidosis 1989;6:44–6. [4] Baughman RP, Drent M, Kavuru M, et al. Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement. Am J Respir Crit Care Med 2006;174:795–802. [5] Verschueren K, Van Essche E, Verschueren P, et al. Development of sarcoidosis in etanercept-treated rheumatoid arthritis patients. Clin Rheumatol 2007;26:1969–71. [6] Gonzalez-Lopez MA, Blanco R, Gonzalez-Vela MC, et al. Development of sarcoidosis during etanercept therapy. Arthritis Rheum 2006;55:817–20. [7] Ahmad K, Rogers S. Development of Crohn disease in a patient on etanercept for psoriasis. Br J Dermatol 2007;157:396. [8] Wallis RS, Broder MS, Wong JY, et al. Granulomatous infectious diseases associated with tumor necrosis factor antagonists. Clin Infect Dis 2004;38:1261–5. [9] Almodovar R, Izquierdo M, Zarco P, et al. Pulmonary sarcoidosis in a patient with ankylosing spondylitis treated with infliximab. Clin Exp Rheumatol 2007;25:99–101.
719
[10] O’Shea FD, Marras TK, Inman RD. Pulmonary sarcoidosis developing during infliximab therapy. Arthritis Rheum 2006;55:978–81.
Séverine Josse a Nathalie Klemmer a,∗ Sophie Moreno-Swirc b Vincent Goëb c Thierry Lequerré c Olivier Vittecoq c a Department of Rheumatology, Rouen University Hospital, 76031 Rouen cedex, France b Department of Anatomopathology, Rouen University Hospital, 76031 Rouen cedex, France c Inserm U905, (IFRMP23), Department of Rheumatology, Rouen University Hospital, Institute for Biomedical Research, University of Rouen, 76031 Rouen cedex, France ∗ Corresponding
author. E-mail addresses: [email protected], [email protected] (N. Klemmer). 24 February 2009 Available online 21 May 2009 doi:10.1016/j.jbspin.2009.02.003
The comparison of phonophoresis, iontophoresis and local steroid injection in carpal tunnel syndrome treatment
Keywords: Carpal tunnel syndrome; Local steroid injection; Iontophoresis; Phonophoresis; Conservative treatment
Carpal tunnel syndrome (CTS) is an entrapment neuropathy and occurs by compression of median nerve at the wrist [1]. The positive effects of steroid injection therapy on the disease symptoms have been reported in many studies [2,3]. Iontophoresis and phonophoresis are popular methods in transdermal medication delivery [4]. Transdermal steroid administration may eliminate potential side effects which can occur with medication delivered by injection. Therefore, this study was performed to compare the efficacy of transdermal steroid therapies with local steroid injection (LSI), a treatment of known effectiveness for in CTS. Forty-five patients (90 hands) with bilateral early-mild CTS were included. Patients were randomly divided into three groups: LSI (n = 15), steroid iontophoresis (SI) (n = 15) and steroid phonophoresis (SP) (n = 15) groups. Patients were evaluated for clinical (nocturnal pain and Boston Questionnaire [BQ] [5]) and electrophysiological examinations at baseline, 1 and 6 months after treatment. In the group LSI, 4 mg dexamethasone without local anaesthetic was injected. 0.1% dexamethasone sodium phosphate pomade in 1 MHz frequency, 1 W/cm2 intensity, pulsed mode: 1:4, with a transducer of 5 cm2 was applied for 10 minutes per session in phonophoresis treatment. 1 to 4 mA galvanic current was applied for 10 minutes with 0.4% dexamethasone
720
Letters to the editor / Joint Bone Spine 76 (2009) 718–725
Table 1 Comparison of clinical and electrophysiological data in first and sixth months before treatment in each group and between injection and iontophoresis groups or injection and phonophoresis groups as median (min–max). LSI group
SI group
SP group
P1a
P2b
Nocturnal pain Baseline First month Sixth month
2.00 (1.00–3.00) 1.00 (1.00–2.00)*** 1.00 (1.00–2.00)***
2.00 (1.00–3.00) 1.00 (1.00–3.00)*** 1.00 (1.00–3.00)
2.00 (1.00–3.00) 1.00 (1.00–2.00)*** 1.5 (1.00–3.00)**
p > 0.05 p > 0.05 p = 0.020*
p > 0.05 p > 0.05 p = 0.022*
Symptom severity Baseline First month Sixth month
2.18 (1.45–3.73) 1.09 (1.00–2.45)*** 1.36 (1.00–2.73)***
2.09 (1.64–3.45) 1.64 (1.00–2.91)*** 1.91 (0.91–3.82)
2.68 (1.36–3.82) 1.73 (0.91–3.18)*** 1.82 (1.00–3.27)***
p > 0.05 p = 0.031 p = 0.003*
p > 0.05 p > 0.05 p = 0.030
Functional status Baseline First month Sixth month
1.38 (1.00–3.75) 1.00 (1.00–2.50)*** 1.13 (1.00–2.38)*
1.50 (1.13–2.75) 1.19 (1.00–2.75)*** 1.38 (1.00–3.50)
1.88 (1.00–3.25) 1.06 (1.00–2.50)*** 1.38 (1.00–2.63)**
p > 0.05 p > 0.05 p = 0.011*
p > 0.05 p > 0.05 p > 0.05
DSL Baseline First month Sixth month
4.10 (3.70–4.90) 3.70 (3.10–4.70)*** 3.70 (3.00–4.90)***
3.90 (3.60–4.90) 3.90 (3.10–4.90) 3.90 (3.10–4.90)
3.90 (3.70–4.80) 3.80 (3.10–4.50)*** 3.95 (3.30–4.80)
p > 0.05 p = 0.036 p > 0.05
p > 0.05 p > 0.05 p > 0.05
DML Baseline First month Sixth month
4.20 (3.30–8.90) 3.95 (3.00–8.90)*** 3.95 (3.00–9.00)***
4.05 (3.20–9.10) 4.00 (3.40–9.00) 4.15 (3.30–9.00)
4.15 (3.50–5.80) 4.10 (3.20–5.70)* 4.15 (3.20–5.70)
p > 0.05 p > 0.05 p > 0.05
p > 0.05 p > 0.05 p > 0.05
DSL: distal sensory latency; DML: distal motor latency. * p < 0.01, ** p = 0.001, *** p < 0.001; Compare with baseline values. *p < 0.025: values with p < 0.025 were accepted as statistically significant according to Bonferroni adjustment for Friedman and Wilcoxon-rank tests. a P1: Significance level of changes, between injection and iontophoresis groups. b P2: Significance level of changes, between injection and phonophoresis groups.
sodium phosphate in iontophoresis treatment. Iontophoresis and phonophoresis were applied five sessions per week for three weeks. Wrist splint was not used. At the first follow-up, statistically significant improvements were determined in both clinical parameters and electrophysiological data (distal sensory latencies [DSL] and distal motor latencies [DML]) in the LSI and SP groups (p < 0.001). In group SI, significant changes were only recorded in clinical parameters (p < 0.001). Whereas in group LSI, the values of all parameters remained significant at the sixth month (p < 0.001), but not in SI group, significant differences were found only in clinical parameters in group SP (p < 0.01) (Table 1). The effectiveness on electrophysiological data and duration of benefit of steroid injection has not been clarified yet. We performed another small study and compared the efficacy of LSI, iontophoresis and phonophoresis on CTS treatment using different mean nerve conduction parameters [6]. We have reported that the most significant improvement was observed in injection group at 4-month follow-up. In this study, important improvement remained in group LSI for 6 months. These results indicate that local steroid administration causes considerable symptomatic relief in CTS, but differences in the duration of positive effects on symptoms and electrophysiological changes seem to be related to delivery of the medication. Banta [7] applied dexamethasone sodium phosphate iontophoresis on CTS treatment and obtained successful results in 58% of cases for 6-month period. However, patients received ibuprofen and they used wrist splint. Göko˘glu et al. [8] compared
the efficacy of LSI and SI for 2 months. The most improvement was observed in the injection group. We could not find any study showing the effect of SP on CTS treatment in Medline database. The effect of ultrasound should be taken into account in results of SP. As a result, LSI is an effective method on both symptoms and nerve conduction in short and middle term in early-mild CTS treatment. However, similar effect was obtained with SP, that is a less painful method. SP, as steroid injection, seems to be a usable method to relieve symptoms in CTS treatment for short term. References [1] Atroshi I, Gummesson C, Johnsson R, et al. Prevalence of carpal tunnel syndrome in a general population. JAMA 1999;282:153–8. [2] Marshall S, Tardif G, Ashworth N. Local corticosteroid injection for carpal tunnel syndrome. Cochrane Database Syst Rev 2002;4:CD001554. [3] Girlanda P, Dattola R, Venuto C, et al. Local steroid treatment in idiopathic carpal tunnel syndrome: short- and long-term efficacy. J Neurol 1993;240:187–90. [4] Brown MB, Martin GP, Jones SA, et al. Dermal and transdermal drug delivery systems: current and future prospects. Drug Deliv 2006;13:175–87. [5] Levine DW, Simmons BP, Koris MJ, et al. A self-administered questionnaire for the assessment of severity of symptoms and functional status in carpal tunnel syndrome. J Bone Joint Surg Am 1993;75: 1585–92. [6] Aygul R, Ulvi H, Karatay S, et al. Determination of sensitive electrophysiologic parameters at follow-up of different steroid treatments of carpal tunnel syndrome. J Clin Neurophysiol 2005;22:222–30. [7] Banta CA. A prospective, nonrandomized study of iontophoresis, wrist splinting, and anti-inflammatory medication in the treatment of early-mild carpal tunnel syndrome. J Occup Med 1994;36:166–8.
Letters to the editor / Joint Bone Spine 76 (2009) 718–725 [8] Göko˘glu F, Fndko˘glu G, Yorganco˘glu ZR, et al. Evaluation of iontophoresis and local corticosteroid injection in the treatment of carpal tunnel syndrome. Am J Phys Med Rehabil 2005;84:92–6.
Saliha Karatay a,∗ Recep Aygul b Meltem Alkan Melikoglu a Kadir Yildirim a Mahir Ugur a Akin Erdal a Selami Akkus c Kazım S¸enel a a Departments of Physical Medicine and Rehabilitation, Medical Faculty, Ataturk University, 25240 Erzurum, Turkey b Departments of Neurology, Medical Faculty, Ataturk University, Erzurum, Turkey c Departments of Physical Medicine and Rehabilitation, Medical Faculty, Suleyman Demirel University, Isparta, Turkey ∗ Corresponding
author. E-mail address: [email protected] (S. Karatay). 24 February 2009 Available online 7 July 2009 doi:10.1016/j.jbspin.2009.02.008
721
and from PCR assays for HHV8 and HIV material in blood. The blood cell count showed polyclonal lymphopenia (908 lymphocytes/mm3 ). Investigations including bronchoscopy and computed tomography of the chest, abdomen, and pelvis identified no additional lesions. The diagnosis was HHV8-positive Kaposi’s disease confined to the skin, with onset during TNF␣ therapy (adalimumab). The pathophysiology of Kaposi’s disease is debated. Recent studies suggest reactive cell proliferation, perhaps in response to HHV8 infection, rather than a true malignant process with metastatic dissemination [1]. Our patient is the second reported case of HHV8-positive cutaneous Kaposi’s disease during immunosuppressive therapy with a monoclonal antibody against TNF␣. The other patient was a 69-year-old woman on infliximab and glucocorticoid therapy for rheumatoid arthritis [2]. Features shared with our patient include the onset early after treatment initiation and the negative tests for the HIV. Iatrogenic immunodepression is the second most common cause of Kaposi’s disease. This adverse event chiefly targets organ transplant recipients [3] and is far less common in patients with inflammatory joint disease. Our patient had no history of glucocorticoid therapy, and the timing of the event indicates a causal role for adalimumab therapy. Interestingly, the patient had no evidence of Kaposi’s disease during 3 years of treatment with etanercept. This fact may be related to the different pathways by which these two drugs cause TNF␣ inhibition. Several studies found higher risks of bacterial and viral infections in patients taking monoclonal antibodies compared to those taking the soluble receptor [4–6].
Kaposi’s disease in a patient on adalimumab for rheumatoid arthritis References Keywords: Sarcoma; Kaposi’s disease; Rheumatoid arthritis; TNF-alpha antagonists; Adalimumab
TNF␣ inhibition is effective but increases the risk of infection. We report the second case of Kaposi’s disease in a patient taking TNF␣ antagonist therapy for rheumatoid arthritis. This 67-year-old homosexual man had an unremarkable medical history except for rheumatoid arthritis diagnosed 4 years earlier. Hydroxychloroquine and methotrexate were used successively, to no effect. The soluble receptor etanercept combined with methotrexate then provided a remission, which lasted 2 years. Tolerance was acceptable. Escape phenomenon developed, prompting the substitution of the monoclonal antibody adalimumab for the etanercept, with no change in the methotrexate regimen. Two months later, skin lesions developed. Purple nodules, about 20 to 30 in all, were visible over the torso and limbs. There was no pruritus. A biopsy showed that the superficial and intermediate dermis contained an abundant cell population consisting of lymphocytes, plasma cells, and spindleshaped cells, between which extravasated erythrocytes were visible. Immunohistochemical studies identified spindle-shaped cells that were positive for the human herpes virus (HHV) 8. Findings were negative from serological tests for the HIV
[1] Duprez R, Lacoste V, Briere J, et al. Evidence for a multiclonal origin of multicentric advanced lesions of Kaposi sarcoma. J Natl Cancer Inst 2007;99:1086–94. [2] Cohen CD, Horster S, Sander CA, et al. Kaposi’s sarcoma associated with tumour necrosis factor alpha neutralising therapy. Ann Rheum Dis 2003;62:684. [3] Penn I. Kaposi’s sarcoma in transplant recipients. Transplantation 1997;64:669–73. [4] Curtis JR, Xi J, Patkar N, et al. Drug-specific and time-dependent risks of bacterial infection among patients with rheumatoid arthritis who were exposed to tumor necrosis factor alpha antagonists. Arthritis Rheum 2007;56: 4226–7. [5] Strangfeld A, Listing J, Herzer P, et al. Risk of herpes zoster in patients with rheumatoid arthritis treated with anti-TNF␣ agents. JAMA 2009;301:737–44. [6] Wendling D, Streit G, Toussirot E, et al. Herpes zoster in patients taking TNF alpha antagonists for chronic inflammatory joint disease. Joint Bone Spine 2008;75:540–3.
Johan Bret a Julie Hernandez a Christian Aquilina b Laurent Zabraniecki a Bernard Fournie a,∗ a Service de rhumatologie, CHU Purpan, 1, place du Dr-Baylac, 31059 Toulouse, France
We concluded to infliximab induced skin and pulmonary sarcoidosis in a RA patient. Infliximab was discontinued in November 2007. Skin lesions have disappeared within 4 months, pulmonary lesions are regressing. In May 2008, rituximab treatment was initiated because of a new flare of RA (DAS28 = 7.26). TNF␣ plays a key role in the pathogenesis of RA [1] and sarcoidosis [2]. TNF␣ and IL-1 are released by alveolar macrophages in sarcoidosis with active lung involvement [3]. Anti-TNF␣ monoclonal antibodies have been used successfully for the treatment of refractory sarcoidosis with or without lung involvement [4]. 2. Discussion We describe the first case of infliximab induced skin and pulmonary sarcoidosis in a RA patient. Almost all case reports of anti-TNF␣ induced sarcoidosis are due to etanercept [5,6] which is known to induce granulomatous diseases such as Crohn disease [7]. These discrepancies observed between monoclonal antibodies and soluble receptors are potentially linked to their differences in term of mechanism of action. In this regard, anti-TNF␣ monoclonal antibodies have been shown to induce more tuberculosis than etanercept [8]. Emergence of a granulomatous disease with infliximab is surprising since these molecules are effective on diseases associated to granulomatous lesions [3]. Only two case reports of sarcoidosis induced by infliximab have been found in literature, none with skin involvement [9,10]. The disappearance of lesions after discontinuation of infliximab is a strong argument for the diagnosis of drug-induced sarcoidosis. Reintroduction of a TNF␣ blocking agent seems unreasonable. In this context, rituximab was introduced for the management of the active RA of our patient. References [1] Matsuno H, Yudoh K, Katayama R, et al. The role of TNF-alpha in the pathogenesis of inflammation and joint destruction in rheumatoid arthritis (RA): a study using a human RA/SCID mouse chimera. Rheumatology (Oxford) 2002;41:329–37. [2] Sweiss NJ, Curran J, Baughman RP. Sarcoidosis, role of tumor necrosis factor inhibitors and other biologic agents, past, present, and future concepts. Clin Dermatol 2007;25:341–6. [3] Todisco T, Vecchiarelli A, Dottorini M, et al. Sarcoidosis: an alveolar macrophage disease? Sarcoidosis 1989;6:44–6. [4] Baughman RP, Drent M, Kavuru M, et al. Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement. Am J Respir Crit Care Med 2006;174:795–802. [5] Verschueren K, Van Essche E, Verschueren P, et al. Development of sarcoidosis in etanercept-treated rheumatoid arthritis patients. Clin Rheumatol 2007;26:1969–71. [6] Gonzalez-Lopez MA, Blanco R, Gonzalez-Vela MC, et al. Development of sarcoidosis during etanercept therapy. Arthritis Rheum 2006;55:817–20. [7] Ahmad K, Rogers S. Development of Crohn disease in a patient on etanercept for psoriasis. Br J Dermatol 2007;157:396. [8] Wallis RS, Broder MS, Wong JY, et al. Granulomatous infectious diseases associated with tumor necrosis factor antagonists. Clin Infect Dis 2004;38:1261–5. [9] Almodovar R, Izquierdo M, Zarco P, et al. Pulmonary sarcoidosis in a patient with ankylosing spondylitis treated with infliximab. Clin Exp Rheumatol 2007;25:99–101.
719
[10] O’Shea FD, Marras TK, Inman RD. Pulmonary sarcoidosis developing during infliximab therapy. Arthritis Rheum 2006;55:978–81.
Séverine Josse a Nathalie Klemmer a,∗ Sophie Moreno-Swirc b Vincent Goëb c Thierry Lequerré c Olivier Vittecoq c a Department of Rheumatology, Rouen University Hospital, 76031 Rouen cedex, France b Department of Anatomopathology, Rouen University Hospital, 76031 Rouen cedex, France c Inserm U905, (IFRMP23), Department of Rheumatology, Rouen University Hospital, Institute for Biomedical Research, University of Rouen, 76031 Rouen cedex, France ∗ Corresponding
author. E-mail addresses: [email protected], [email protected] (N. Klemmer). 24 February 2009 Available online 21 May 2009 doi:10.1016/j.jbspin.2009.02.003
The comparison of phonophoresis, iontophoresis and local steroid injection in carpal tunnel syndrome treatment
Keywords: Carpal tunnel syndrome; Local steroid injection; Iontophoresis; Phonophoresis; Conservative treatment
Carpal tunnel syndrome (CTS) is an entrapment neuropathy and occurs by compression of median nerve at the wrist [1]. The positive effects of steroid injection therapy on the disease symptoms have been reported in many studies [2,3]. Iontophoresis and phonophoresis are popular methods in transdermal medication delivery [4]. Transdermal steroid administration may eliminate potential side effects which can occur with medication delivered by injection. Therefore, this study was performed to compare the efficacy of transdermal steroid therapies with local steroid injection (LSI), a treatment of known effectiveness for in CTS. Forty-five patients (90 hands) with bilateral early-mild CTS were included. Patients were randomly divided into three groups: LSI (n = 15), steroid iontophoresis (SI) (n = 15) and steroid phonophoresis (SP) (n = 15) groups. Patients were evaluated for clinical (nocturnal pain and Boston Questionnaire [BQ] [5]) and electrophysiological examinations at baseline, 1 and 6 months after treatment. In the group LSI, 4 mg dexamethasone without local anaesthetic was injected. 0.1% dexamethasone sodium phosphate pomade in 1 MHz frequency, 1 W/cm2 intensity, pulsed mode: 1:4, with a transducer of 5 cm2 was applied for 10 minutes per session in phonophoresis treatment. 1 to 4 mA galvanic current was applied for 10 minutes with 0.4% dexamethasone
720
Letters to the editor / Joint Bone Spine 76 (2009) 718–725
Table 1 Comparison of clinical and electrophysiological data in first and sixth months before treatment in each group and between injection and iontophoresis groups or injection and phonophoresis groups as median (min–max). LSI group
SI group
SP group
P1a
P2b
Nocturnal pain Baseline First month Sixth month
2.00 (1.00–3.00) 1.00 (1.00–2.00)*** 1.00 (1.00–2.00)***
2.00 (1.00–3.00) 1.00 (1.00–3.00)*** 1.00 (1.00–3.00)
2.00 (1.00–3.00) 1.00 (1.00–2.00)*** 1.5 (1.00–3.00)**
p > 0.05 p > 0.05 p = 0.020*
p > 0.05 p > 0.05 p = 0.022*
Symptom severity Baseline First month Sixth month
2.18 (1.45–3.73) 1.09 (1.00–2.45)*** 1.36 (1.00–2.73)***
2.09 (1.64–3.45) 1.64 (1.00–2.91)*** 1.91 (0.91–3.82)
2.68 (1.36–3.82) 1.73 (0.91–3.18)*** 1.82 (1.00–3.27)***
p > 0.05 p = 0.031 p = 0.003*
p > 0.05 p > 0.05 p = 0.030
Functional status Baseline First month Sixth month
1.38 (1.00–3.75) 1.00 (1.00–2.50)*** 1.13 (1.00–2.38)*
1.50 (1.13–2.75) 1.19 (1.00–2.75)*** 1.38 (1.00–3.50)
1.88 (1.00–3.25) 1.06 (1.00–2.50)*** 1.38 (1.00–2.63)**
p > 0.05 p > 0.05 p = 0.011*
p > 0.05 p > 0.05 p > 0.05
DSL Baseline First month Sixth month
4.10 (3.70–4.90) 3.70 (3.10–4.70)*** 3.70 (3.00–4.90)***
3.90 (3.60–4.90) 3.90 (3.10–4.90) 3.90 (3.10–4.90)
3.90 (3.70–4.80) 3.80 (3.10–4.50)*** 3.95 (3.30–4.80)
p > 0.05 p = 0.036 p > 0.05
p > 0.05 p > 0.05 p > 0.05
DML Baseline First month Sixth month
4.20 (3.30–8.90) 3.95 (3.00–8.90)*** 3.95 (3.00–9.00)***
4.05 (3.20–9.10) 4.00 (3.40–9.00) 4.15 (3.30–9.00)
4.15 (3.50–5.80) 4.10 (3.20–5.70)* 4.15 (3.20–5.70)
p > 0.05 p > 0.05 p > 0.05
p > 0.05 p > 0.05 p > 0.05
DSL: distal sensory latency; DML: distal motor latency. * p < 0.01, ** p = 0.001, *** p < 0.001; Compare with baseline values. *p < 0.025: values with p < 0.025 were accepted as statistically significant according to Bonferroni adjustment for Friedman and Wilcoxon-rank tests. a P1: Significance level of changes, between injection and iontophoresis groups. b P2: Significance level of changes, between injection and phonophoresis groups.
sodium phosphate in iontophoresis treatment. Iontophoresis and phonophoresis were applied five sessions per week for three weeks. Wrist splint was not used. At the first follow-up, statistically significant improvements were determined in both clinical parameters and electrophysiological data (distal sensory latencies [DSL] and distal motor latencies [DML]) in the LSI and SP groups (p < 0.001). In group SI, significant changes were only recorded in clinical parameters (p < 0.001). Whereas in group LSI, the values of all parameters remained significant at the sixth month (p < 0.001), but not in SI group, significant differences were found only in clinical parameters in group SP (p < 0.01) (Table 1). The effectiveness on electrophysiological data and duration of benefit of steroid injection has not been clarified yet. We performed another small study and compared the efficacy of LSI, iontophoresis and phonophoresis on CTS treatment using different mean nerve conduction parameters [6]. We have reported that the most significant improvement was observed in injection group at 4-month follow-up. In this study, important improvement remained in group LSI for 6 months. These results indicate that local steroid administration causes considerable symptomatic relief in CTS, but differences in the duration of positive effects on symptoms and electrophysiological changes seem to be related to delivery of the medication. Banta [7] applied dexamethasone sodium phosphate iontophoresis on CTS treatment and obtained successful results in 58% of cases for 6-month period. However, patients received ibuprofen and they used wrist splint. Göko˘glu et al. [8] compared
the efficacy of LSI and SI for 2 months. The most improvement was observed in the injection group. We could not find any study showing the effect of SP on CTS treatment in Medline database. The effect of ultrasound should be taken into account in results of SP. As a result, LSI is an effective method on both symptoms and nerve conduction in short and middle term in early-mild CTS treatment. However, similar effect was obtained with SP, that is a less painful method. SP, as steroid injection, seems to be a usable method to relieve symptoms in CTS treatment for short term. References [1] Atroshi I, Gummesson C, Johnsson R, et al. Prevalence of carpal tunnel syndrome in a general population. JAMA 1999;282:153–8. [2] Marshall S, Tardif G, Ashworth N. Local corticosteroid injection for carpal tunnel syndrome. Cochrane Database Syst Rev 2002;4:CD001554. [3] Girlanda P, Dattola R, Venuto C, et al. Local steroid treatment in idiopathic carpal tunnel syndrome: short- and long-term efficacy. J Neurol 1993;240:187–90. [4] Brown MB, Martin GP, Jones SA, et al. Dermal and transdermal drug delivery systems: current and future prospects. Drug Deliv 2006;13:175–87. [5] Levine DW, Simmons BP, Koris MJ, et al. A self-administered questionnaire for the assessment of severity of symptoms and functional status in carpal tunnel syndrome. J Bone Joint Surg Am 1993;75: 1585–92. [6] Aygul R, Ulvi H, Karatay S, et al. Determination of sensitive electrophysiologic parameters at follow-up of different steroid treatments of carpal tunnel syndrome. J Clin Neurophysiol 2005;22:222–30. [7] Banta CA. A prospective, nonrandomized study of iontophoresis, wrist splinting, and anti-inflammatory medication in the treatment of early-mild carpal tunnel syndrome. J Occup Med 1994;36:166–8.
Letters to the editor / Joint Bone Spine 76 (2009) 718–725 [8] Göko˘glu F, Fndko˘glu G, Yorganco˘glu ZR, et al. Evaluation of iontophoresis and local corticosteroid injection in the treatment of carpal tunnel syndrome. Am J Phys Med Rehabil 2005;84:92–6.
Saliha Karatay a,∗ Recep Aygul b Meltem Alkan Melikoglu a Kadir Yildirim a Mahir Ugur a Akin Erdal a Selami Akkus c Kazım S¸enel a a Departments of Physical Medicine and Rehabilitation, Medical Faculty, Ataturk University, 25240 Erzurum, Turkey b Departments of Neurology, Medical Faculty, Ataturk University, Erzurum, Turkey c Departments of Physical Medicine and Rehabilitation, Medical Faculty, Suleyman Demirel University, Isparta, Turkey ∗ Corresponding
author. E-mail address: [email protected] (S. Karatay). 24 February 2009 Available online 7 July 2009 doi:10.1016/j.jbspin.2009.02.008
721
and from PCR assays for HHV8 and HIV material in blood. The blood cell count showed polyclonal lymphopenia (908 lymphocytes/mm3 ). Investigations including bronchoscopy and computed tomography of the chest, abdomen, and pelvis identified no additional lesions. The diagnosis was HHV8-positive Kaposi’s disease confined to the skin, with onset during TNF␣ therapy (adalimumab). The pathophysiology of Kaposi’s disease is debated. Recent studies suggest reactive cell proliferation, perhaps in response to HHV8 infection, rather than a true malignant process with metastatic dissemination [1]. Our patient is the second reported case of HHV8-positive cutaneous Kaposi’s disease during immunosuppressive therapy with a monoclonal antibody against TNF␣. The other patient was a 69-year-old woman on infliximab and glucocorticoid therapy for rheumatoid arthritis [2]. Features shared with our patient include the onset early after treatment initiation and the negative tests for the HIV. Iatrogenic immunodepression is the second most common cause of Kaposi’s disease. This adverse event chiefly targets organ transplant recipients [3] and is far less common in patients with inflammatory joint disease. Our patient had no history of glucocorticoid therapy, and the timing of the event indicates a causal role for adalimumab therapy. Interestingly, the patient had no evidence of Kaposi’s disease during 3 years of treatment with etanercept. This fact may be related to the different pathways by which these two drugs cause TNF␣ inhibition. Several studies found higher risks of bacterial and viral infections in patients taking monoclonal antibodies compared to those taking the soluble receptor [4–6].
Kaposi’s disease in a patient on adalimumab for rheumatoid arthritis References Keywords: Sarcoma; Kaposi’s disease; Rheumatoid arthritis; TNF-alpha antagonists; Adalimumab
TNF␣ inhibition is effective but increases the risk of infection. We report the second case of Kaposi’s disease in a patient taking TNF␣ antagonist therapy for rheumatoid arthritis. This 67-year-old homosexual man had an unremarkable medical history except for rheumatoid arthritis diagnosed 4 years earlier. Hydroxychloroquine and methotrexate were used successively, to no effect. The soluble receptor etanercept combined with methotrexate then provided a remission, which lasted 2 years. Tolerance was acceptable. Escape phenomenon developed, prompting the substitution of the monoclonal antibody adalimumab for the etanercept, with no change in the methotrexate regimen. Two months later, skin lesions developed. Purple nodules, about 20 to 30 in all, were visible over the torso and limbs. There was no pruritus. A biopsy showed that the superficial and intermediate dermis contained an abundant cell population consisting of lymphocytes, plasma cells, and spindleshaped cells, between which extravasated erythrocytes were visible. Immunohistochemical studies identified spindle-shaped cells that were positive for the human herpes virus (HHV) 8. Findings were negative from serological tests for the HIV
[1] Duprez R, Lacoste V, Briere J, et al. Evidence for a multiclonal origin of multicentric advanced lesions of Kaposi sarcoma. J Natl Cancer Inst 2007;99:1086–94. [2] Cohen CD, Horster S, Sander CA, et al. Kaposi’s sarcoma associated with tumour necrosis factor alpha neutralising therapy. Ann Rheum Dis 2003;62:684. [3] Penn I. Kaposi’s sarcoma in transplant recipients. Transplantation 1997;64:669–73. [4] Curtis JR, Xi J, Patkar N, et al. Drug-specific and time-dependent risks of bacterial infection among patients with rheumatoid arthritis who were exposed to tumor necrosis factor alpha antagonists. Arthritis Rheum 2007;56: 4226–7. [5] Strangfeld A, Listing J, Herzer P, et al. Risk of herpes zoster in patients with rheumatoid arthritis treated with anti-TNF␣ agents. JAMA 2009;301:737–44. [6] Wendling D, Streit G, Toussirot E, et al. Herpes zoster in patients taking TNF alpha antagonists for chronic inflammatory joint disease. Joint Bone Spine 2008;75:540–3.
Johan Bret a Julie Hernandez a Christian Aquilina b Laurent Zabraniecki a Bernard Fournie a,∗ a Service de rhumatologie, CHU Purpan, 1, place du Dr-Baylac, 31059 Toulouse, France