previous sensitization and eczematous skin reactions or atypical granulomatous eruptions. Ingo Kleiter, MD1 Heinrich Dickel, MD2 Silas Paras Soemantri, MD2 € rnke, MD1 Christian Bo Departments of 1Neurology and 2Dermatology, Venereology and Allergology, St. Josef-Hospital, Ruhr-University, Bochum, Germany
FIGURE 1. Allergic contact granulomas 8 weeks after EMG at points of needle insertion. First dorsal interosseous (A) and tibialis anterior (B) muscle on the left side are shown.
insertion points with subsequent blistering and granulomatous, non-eczematous eruptions (Fig. 1). The disposable concentric needle electrodes used in the EMG examination consisted of stainless-steel, platinum, and palladium. Patch testing was performed on the upper back with the German Contact Dermatitis Research Group (DKG) standard series and the DKG dental metal series.1 Positive reactions to palladium chloride (1.0% pet.) and ammonium tetrachloroplatinate (0.25% pet.) were observed at 72- and 168-hour readings. No positive reactions were observed to any of the other 36 test substances. Sensitization may have occurred some years ago, when she wore a platinum piercing in the left eyebrow, which was removed due to persistent local inflammation. EMG and nerve conduction studies with needle electrodes may be associated with iatrogenic complications such as bleeding, infection, nerve injury, pneumothorax, urticaria, and complex regional pain syndrome.2–4 Although metal allergies are a well-known problem,5,6 they are probably rare after EMG. We could only find a single report of an EMG-associated allergic contact dermatitis, in which nickel could be identified as the allergen.7 In our patient, clinical signs of a delayed-type hypersensitivity reaction occurred at all needle electrode insertion points. They appeared as painful swelling and subsequent prominent granulomatous eruptions that persisted for several weeks. It is noteworthy that, unlike typical allergic contact dermatitis, the skin lesions were non-eczematous. Allergic reactions to 2 metals contained in the needle electrodes, platinum and palladium, were proven by patch testing. Delayed-type hypersensitivity reactions are T-cell driven and can include several metals due to crossreactivity, as in our patient.8 Because metal ions are haptens and are considered to be incomplete antigens, protein or peptide binding is needed for immunogenicity. Persistent local inflammation may have facilitated the generation of a metal-specific T-cell response in this patient. Treatment of contact dermatitis includes local steroid therapy and strict allergen avoidance.5 In conclusion, an allergic contact dermatitis to EMG needle electrodes should be considered in patients with 868
Letters to the Editor
1. Schnuch A, Aberer W, Agathos M, Becker D, Brasch J, Elsner P, et al. Performing patch testing with contact allergens [in German]. J Dtsch Dermatol Ges 2008;6:770–775. 2. Al-Shekhlee A, Shapiro BE, Preston DC. Iatrogenic complications and risks of nerve conduction studies and needle electromyography. Muscle Nerve 2003;27:517–526. 3. Lynch SL, Boon AJ, Smith J, Harper CM Jr, Tanaka EM. Complications of needle electromyography: hematoma risk and correlation with anticoagulation and antiplatelet therapy. Muscle Nerve 2008;38: 1225–1230. 4. Tankisi H, Terkelsen AJ, Fuglsang-Frederiksen A. complex regional pain syndrome as a complication to electroneuronography. Clin Neurophysiol 2010;121:980–983. 5. Becker D. Allergic contact dermatitis. J Dtsch Dermatol Ges 2013;11: 607–619. 6. Hamann D, Hamann CR, Thyssen JP. The impact of common metal allergens in daily devices. Curr Opin Allergy Clin Immunol 2013;13:525–530. 7. Bragadin G, Taraschi A, Marchini C, Mucchiut M, Patrone P. Allergic contact dermatitis from nickel following electromyography. Contact Dermatitis 1999;41:353–354. 8. Budinger L, Hertl M. Immunologic mechanisms in hypersensitivity reactions to metal ions: an overview. Allergy 2000;55: 108–115.
Published online 11 July 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/mus.24339
---------------------------------------------------------
ACUTE INFLAMMATORY DEMYELINATING POLYRADICULOPATHY IN LEGIONELLA PNEUMONIA Legionella pneumophila is a non-encapsulated gram-negative bacillus with clinical features that have been linked classically to extrapulmonary manifestations. Of these features, encephalopathy is a common neurologic association. More serious neurologic findings are usually rare, and reports of other neurologic involvement are uncommon. A 71-year-old man with a history of atrial fibrillation presented with a 5-day history of nausea and vomiting with profuse diarrhea, intermittent fever, and lethargy. On evaluation, he appeared to be in moderate distress and was noted to be confused. On auscultation, his lungs exhibited decreased breath sounds in the bilateral bases, and his heart had an irregularly irregular rhythm without murmurs or gallops. His neurologic exam demonstrated intact cranial nerves II–XII, although he had left strabismus, which was long-standing. However, he had bilateral symmetric weakness in the lower extremities with absent deep tendon reflexes at the knees and ankles. There was also diminished nociception and vibratory sensation in the lower extremities. Laboratory findings did not exhibit leukocytosis, and serum chemistries were normal except for a mild elevation of serum creatinine to 1.49 mg/dl (from a baseline MUSCLE & NERVE
November 2014
of 1.0 mg/dl) (normal, 0.6–1.3 mg/dl). He also had a serum lactate of 2.0 mmol/L (normal, 0.4–2.0 mmol/L). Given his symptoms of nausea, vomiting, and profuse diarrhea, he underwent an abdominal CT that did not reveal any acute abdominal abnormalities, but a right lower lobe infiltrate was visualized in the lung fields. A Legionella pneumophila serogroup 1 urine antigen qualitative rapid assay was positive, and he was treated with levofloxacin. His weakness did not improve in response to treatment. Given his history of atrial fibrillation for which he is on warfarin, his INR remained elevated in therapeutic as well as supratherapeutic ranges once antibiotics were initiated (INR 4.8), which precluded a safe lumbar puncture. Instead, an electromyogram and nerve conduction study was obtained on day 5 of his hospitalization to evaluate his bilateral lower extremity weakness. This study demonstrated increased insertional activity with fibrillation potentials together with large polyphasic motor unit potentials and mild to moderate reduction in recruitment of left tibialis anterior, medial gastrocnemius, first dorsal interosseus, and biceps muscles. Nerve conduction study showed absent F-waves or delayed latencies, motor conduction block, reduced compound motor action potential amplitudes, and delayed sensory nerve action potential onset and latencies and amplitudes suggestive of an acute demyelinating polyradiculopathy. He was treated on day 6 of his hospitalization with a 5-day course of intravenous immunoglobulin, which was associated with complete restoration of sensorimotor function. He was discharged from the hospital on day 14. To date, several extrapulmonary manifestations have been reported from outbreaks caused by Legionella pneumophila. Of the neurologic manifestations, encephalopathy is the most common and appears to be a characteristic manifestation of Legionella pneumonia.1,2 More recently, there have been reports of cranial nerve deficits3,4 and acute disseminated encephalomyelitis.5 Gullain-Barre syndrome (GBS) manifesting as an acute demyelinating polyradiculopathy in the setting of Legionella pneumophila infection has only been reported in children and adolescents.6,7 Currently, there have not been any reports of GBS occurring in the setting of an acute Legionella infection in adults in the English-language medical literature. The mechanism by which Legionella pneumophila can cause an acute inflammatory demyelinating polyradiculopathy has not been elucidated, likely due to a lack of recognition of an association between the two entities. With the availability of rapid diagnostic kits, much needed studies on the prevalence of Legionella pneumophila among patients diagnosed with GBS will be easier to perform and, hopefully, will shed insight into any causative associations. Justin K. Lui, MD,1,2 Sunkaru Touray, MD, MSc,1,2 William A. Tosches, MD,2,3 Kathleen Richard, M.D.2 1
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
2
Milford Regional Medical Center, Milford, Massachusetts Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts
3
Letters to the Editor
1. Cunha BA. Legionnaires’ disease: clinical differentiation from typical and other atypical pneumonias. Infect Dis Clin North Am 2010;24: 73–105. 2. Johnson JD, Raff MJ, Van Arsdall JA. Neurologic manifestations of Legionnaires’ disease. Medicine (Baltimore). 1984;63:303–310. 3. Basani SR, Ahmed SM, Habte-Gabr E. Legionnaires’ disease with facial nerve palsy. Case Rep Med 2011;2011:916859. 4. Konno S, Kono H, Kitazono H, Murata M, Nakazora H, Nomoto N, et al. Legionellosis presenting as singultus and external ophthalmoplegia. Neurol Sci 2012;33:1435–1437. 5. de Lau LM1, Siepman DA, Remmers MJ, Terwindt GM, Hintzen RQ. Acute disseminating encephalomyelitis following Legionnaires disease. Arch Neurol 2010;67:623–626. 6. Akyildiz B, G€ um€ us H, Kumandas S, Coskun A, Baykan A, Yikilmaz A, et al. Guillain-Barr e syndrome associated with Legionnella infection. J Trop Pediatr 2008;54:275–277. 7. Canpolat M, Kumandas S, Yikilmaz A, Gumus H, Koseoglu E, Poyrazo glu HG, et al. Transverse myelitis and acute motor sensory axonal neuropathy due to Legionella pneumophila: a case report. Pediatr Int 2013;55:778–782.
Published online 15 July 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/mus.24341
--------------------------------------------------------SAFETY OF BOTULINUM TOXIN FOR DYSPHAGIA IN OCULOPHARYNGEAL MUSCULAR DYSTROPHY In their recent study, Youssof et al. reviewed the health records of their patients with oculopharyngeal muscular dystrophy who had at least 1 cricopharyngeal (CP) botulinum toxin (BTX) injection for treatment of dysphagia. They sought to better characterize the risks associated with CP myotomy by BTX in these patients.1 The following variables were evaluated: age; gender; dose; procedure type; injection site; and time since last injection.1 They was found that worsened dysphagia and dysphonia are dose-related adverse events (AEs) and provide estimates for the magnitude of AE risk at different doses.1 We consider these results to be unsurprising. In fact, we predicted previously that high BTX doses could cause worsened dysphagia and dysphonia through local peripheral toxin diffusion, leading to neuromuscular blockade in nearby untreated muscles.2,3 For this reason, we always use low BTX doses4–10 to avoid neurotoxin diffusion to the adjacent posterior cricoarytenoid muscles with consequent dyspnea or dysphonia or diffusion to the inferior pharyngeal constrictor (IPC) muscle with consequent increased dysphagia.2,4 Youssof et al. suggested that the increased risk depends on the etiology of dysphagia and hypothesized a higher risk in diseases involving the peripheral nerve and muscle. We disagree with the authors on this point. In fact, no significant AEs were observed in patients with oropharyngeal dysphagia associated with diabetic peripheral neuropathy or tetanus, or with myopathy treated with BTX injections in the CP muscle.5–8 A higher risk of AEs may depend on more severe involvement of the voluntary IPC muscles with consequent lack of propulsion of the bolus toward the upper esophagus that in turn induces a further increase of CP hyperactivity.4 There was, however, another variable of major importance in safety evaluation of BTX that was not considered in their analysis—BTX dilution. Neurotoxin dilution is closely related to diffusion into nearby muscles.3 For CP muscle injection, a very low dilution (1 or 2 ml maximum, based on the number of sites to treat and on MUSCLE & NERVE
November 2014
869
FIGURE 1. Allergic contact granulomas 8 weeks after EMG at points of needle insertion. First dorsal interosseous (A) and tibialis anterior (B) muscle on the left side are shown.
insertion points with subsequent blistering and granulomatous, non-eczematous eruptions (Fig. 1). The disposable concentric needle electrodes used in the EMG examination consisted of stainless-steel, platinum, and palladium. Patch testing was performed on the upper back with the German Contact Dermatitis Research Group (DKG) standard series and the DKG dental metal series.1 Positive reactions to palladium chloride (1.0% pet.) and ammonium tetrachloroplatinate (0.25% pet.) were observed at 72- and 168-hour readings. No positive reactions were observed to any of the other 36 test substances. Sensitization may have occurred some years ago, when she wore a platinum piercing in the left eyebrow, which was removed due to persistent local inflammation. EMG and nerve conduction studies with needle electrodes may be associated with iatrogenic complications such as bleeding, infection, nerve injury, pneumothorax, urticaria, and complex regional pain syndrome.2–4 Although metal allergies are a well-known problem,5,6 they are probably rare after EMG. We could only find a single report of an EMG-associated allergic contact dermatitis, in which nickel could be identified as the allergen.7 In our patient, clinical signs of a delayed-type hypersensitivity reaction occurred at all needle electrode insertion points. They appeared as painful swelling and subsequent prominent granulomatous eruptions that persisted for several weeks. It is noteworthy that, unlike typical allergic contact dermatitis, the skin lesions were non-eczematous. Allergic reactions to 2 metals contained in the needle electrodes, platinum and palladium, were proven by patch testing. Delayed-type hypersensitivity reactions are T-cell driven and can include several metals due to crossreactivity, as in our patient.8 Because metal ions are haptens and are considered to be incomplete antigens, protein or peptide binding is needed for immunogenicity. Persistent local inflammation may have facilitated the generation of a metal-specific T-cell response in this patient. Treatment of contact dermatitis includes local steroid therapy and strict allergen avoidance.5 In conclusion, an allergic contact dermatitis to EMG needle electrodes should be considered in patients with 868
Letters to the Editor
1. Schnuch A, Aberer W, Agathos M, Becker D, Brasch J, Elsner P, et al. Performing patch testing with contact allergens [in German]. J Dtsch Dermatol Ges 2008;6:770–775. 2. Al-Shekhlee A, Shapiro BE, Preston DC. Iatrogenic complications and risks of nerve conduction studies and needle electromyography. Muscle Nerve 2003;27:517–526. 3. Lynch SL, Boon AJ, Smith J, Harper CM Jr, Tanaka EM. Complications of needle electromyography: hematoma risk and correlation with anticoagulation and antiplatelet therapy. Muscle Nerve 2008;38: 1225–1230. 4. Tankisi H, Terkelsen AJ, Fuglsang-Frederiksen A. complex regional pain syndrome as a complication to electroneuronography. Clin Neurophysiol 2010;121:980–983. 5. Becker D. Allergic contact dermatitis. J Dtsch Dermatol Ges 2013;11: 607–619. 6. Hamann D, Hamann CR, Thyssen JP. The impact of common metal allergens in daily devices. Curr Opin Allergy Clin Immunol 2013;13:525–530. 7. Bragadin G, Taraschi A, Marchini C, Mucchiut M, Patrone P. Allergic contact dermatitis from nickel following electromyography. Contact Dermatitis 1999;41:353–354. 8. Budinger L, Hertl M. Immunologic mechanisms in hypersensitivity reactions to metal ions: an overview. Allergy 2000;55: 108–115.
Published online 11 July 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/mus.24339
---------------------------------------------------------
ACUTE INFLAMMATORY DEMYELINATING POLYRADICULOPATHY IN LEGIONELLA PNEUMONIA Legionella pneumophila is a non-encapsulated gram-negative bacillus with clinical features that have been linked classically to extrapulmonary manifestations. Of these features, encephalopathy is a common neurologic association. More serious neurologic findings are usually rare, and reports of other neurologic involvement are uncommon. A 71-year-old man with a history of atrial fibrillation presented with a 5-day history of nausea and vomiting with profuse diarrhea, intermittent fever, and lethargy. On evaluation, he appeared to be in moderate distress and was noted to be confused. On auscultation, his lungs exhibited decreased breath sounds in the bilateral bases, and his heart had an irregularly irregular rhythm without murmurs or gallops. His neurologic exam demonstrated intact cranial nerves II–XII, although he had left strabismus, which was long-standing. However, he had bilateral symmetric weakness in the lower extremities with absent deep tendon reflexes at the knees and ankles. There was also diminished nociception and vibratory sensation in the lower extremities. Laboratory findings did not exhibit leukocytosis, and serum chemistries were normal except for a mild elevation of serum creatinine to 1.49 mg/dl (from a baseline MUSCLE & NERVE
November 2014
of 1.0 mg/dl) (normal, 0.6–1.3 mg/dl). He also had a serum lactate of 2.0 mmol/L (normal, 0.4–2.0 mmol/L). Given his symptoms of nausea, vomiting, and profuse diarrhea, he underwent an abdominal CT that did not reveal any acute abdominal abnormalities, but a right lower lobe infiltrate was visualized in the lung fields. A Legionella pneumophila serogroup 1 urine antigen qualitative rapid assay was positive, and he was treated with levofloxacin. His weakness did not improve in response to treatment. Given his history of atrial fibrillation for which he is on warfarin, his INR remained elevated in therapeutic as well as supratherapeutic ranges once antibiotics were initiated (INR 4.8), which precluded a safe lumbar puncture. Instead, an electromyogram and nerve conduction study was obtained on day 5 of his hospitalization to evaluate his bilateral lower extremity weakness. This study demonstrated increased insertional activity with fibrillation potentials together with large polyphasic motor unit potentials and mild to moderate reduction in recruitment of left tibialis anterior, medial gastrocnemius, first dorsal interosseus, and biceps muscles. Nerve conduction study showed absent F-waves or delayed latencies, motor conduction block, reduced compound motor action potential amplitudes, and delayed sensory nerve action potential onset and latencies and amplitudes suggestive of an acute demyelinating polyradiculopathy. He was treated on day 6 of his hospitalization with a 5-day course of intravenous immunoglobulin, which was associated with complete restoration of sensorimotor function. He was discharged from the hospital on day 14. To date, several extrapulmonary manifestations have been reported from outbreaks caused by Legionella pneumophila. Of the neurologic manifestations, encephalopathy is the most common and appears to be a characteristic manifestation of Legionella pneumonia.1,2 More recently, there have been reports of cranial nerve deficits3,4 and acute disseminated encephalomyelitis.5 Gullain-Barre syndrome (GBS) manifesting as an acute demyelinating polyradiculopathy in the setting of Legionella pneumophila infection has only been reported in children and adolescents.6,7 Currently, there have not been any reports of GBS occurring in the setting of an acute Legionella infection in adults in the English-language medical literature. The mechanism by which Legionella pneumophila can cause an acute inflammatory demyelinating polyradiculopathy has not been elucidated, likely due to a lack of recognition of an association between the two entities. With the availability of rapid diagnostic kits, much needed studies on the prevalence of Legionella pneumophila among patients diagnosed with GBS will be easier to perform and, hopefully, will shed insight into any causative associations. Justin K. Lui, MD,1,2 Sunkaru Touray, MD, MSc,1,2 William A. Tosches, MD,2,3 Kathleen Richard, M.D.2 1
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
2
Milford Regional Medical Center, Milford, Massachusetts Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts
3
Letters to the Editor
1. Cunha BA. Legionnaires’ disease: clinical differentiation from typical and other atypical pneumonias. Infect Dis Clin North Am 2010;24: 73–105. 2. Johnson JD, Raff MJ, Van Arsdall JA. Neurologic manifestations of Legionnaires’ disease. Medicine (Baltimore). 1984;63:303–310. 3. Basani SR, Ahmed SM, Habte-Gabr E. Legionnaires’ disease with facial nerve palsy. Case Rep Med 2011;2011:916859. 4. Konno S, Kono H, Kitazono H, Murata M, Nakazora H, Nomoto N, et al. Legionellosis presenting as singultus and external ophthalmoplegia. Neurol Sci 2012;33:1435–1437. 5. de Lau LM1, Siepman DA, Remmers MJ, Terwindt GM, Hintzen RQ. Acute disseminating encephalomyelitis following Legionnaires disease. Arch Neurol 2010;67:623–626. 6. Akyildiz B, G€ um€ us H, Kumandas S, Coskun A, Baykan A, Yikilmaz A, et al. Guillain-Barr e syndrome associated with Legionnella infection. J Trop Pediatr 2008;54:275–277. 7. Canpolat M, Kumandas S, Yikilmaz A, Gumus H, Koseoglu E, Poyrazo glu HG, et al. Transverse myelitis and acute motor sensory axonal neuropathy due to Legionella pneumophila: a case report. Pediatr Int 2013;55:778–782.
Published online 15 July 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/mus.24341
--------------------------------------------------------SAFETY OF BOTULINUM TOXIN FOR DYSPHAGIA IN OCULOPHARYNGEAL MUSCULAR DYSTROPHY In their recent study, Youssof et al. reviewed the health records of their patients with oculopharyngeal muscular dystrophy who had at least 1 cricopharyngeal (CP) botulinum toxin (BTX) injection for treatment of dysphagia. They sought to better characterize the risks associated with CP myotomy by BTX in these patients.1 The following variables were evaluated: age; gender; dose; procedure type; injection site; and time since last injection.1 They was found that worsened dysphagia and dysphonia are dose-related adverse events (AEs) and provide estimates for the magnitude of AE risk at different doses.1 We consider these results to be unsurprising. In fact, we predicted previously that high BTX doses could cause worsened dysphagia and dysphonia through local peripheral toxin diffusion, leading to neuromuscular blockade in nearby untreated muscles.2,3 For this reason, we always use low BTX doses4–10 to avoid neurotoxin diffusion to the adjacent posterior cricoarytenoid muscles with consequent dyspnea or dysphonia or diffusion to the inferior pharyngeal constrictor (IPC) muscle with consequent increased dysphagia.2,4 Youssof et al. suggested that the increased risk depends on the etiology of dysphagia and hypothesized a higher risk in diseases involving the peripheral nerve and muscle. We disagree with the authors on this point. In fact, no significant AEs were observed in patients with oropharyngeal dysphagia associated with diabetic peripheral neuropathy or tetanus, or with myopathy treated with BTX injections in the CP muscle.5–8 A higher risk of AEs may depend on more severe involvement of the voluntary IPC muscles with consequent lack of propulsion of the bolus toward the upper esophagus that in turn induces a further increase of CP hyperactivity.4 There was, however, another variable of major importance in safety evaluation of BTX that was not considered in their analysis—BTX dilution. Neurotoxin dilution is closely related to diffusion into nearby muscles.3 For CP muscle injection, a very low dilution (1 or 2 ml maximum, based on the number of sites to treat and on MUSCLE & NERVE
November 2014
869
