JAGS
OCTOBER 2014–VOL. 62, NO. 10
Eosinophilic colitis is a rare clinical condition, so the most important factor in making the diagnosis is to have a high degree of clinical suspicion. In conclusion, clinicians should consider EC in the differential diagnosis of LGIB in elderly adults, and early medical treatment should be initiated to avoid serious complications. G€ ulay Kocßak, MD Department of Nephrology, C ß anakkale Onsekiz Mart University, C ß anakkale, Turkey Erdem Kocßak, MD Department of Gastroenterology, C ß anakkale State Hospital, C ß anakkale, Turkey Erdem Akbal, MD Department of Gastroenterology, C ß anakkale Onsekiz Mart University, C ß anakkale, Turkey Hacer Sßen, MD G€ okhan Erba g, MD Ceren Erdo gan, MD Department of Internal Medicine, C ß anakkale Onsekiz Mart University, C ß anakkale, Turkey
ACKNOWLEDGMENTS Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: G€ ulay Kocßak: manuscript concept and design. Erdem Kocßak, G€ okhan Erba g: preparation of manuscript. Erdem Akbal, Hacer Sßen: analysis and interpretation of data. Ceren Erdo gan: subject’s doctor. Sponsor’s Role: No sponsor associated with manuscript.
REFERENCES 1. Chait MM. Lower gastrointestinal bleeding in the elderly. World J Gastrointest Endosc 2010;2:147–154. 2. Alfadda AA, Schaffer EA, Urbanski SJ et al. Eosinophilic colitis is a sporadic self-limited disease of middle-aged people: A population-based study. Colorectal Dis 2014;16:123–129. 3. Yeo SA, Lim YK, Lim KH et al. Toxic haemorrhagic colitis: A rare presentation of eosinophilic colitis. Case Rep Gastrointest Med 2012;2012: 279813. 4. Ohtsuka Y, Shimizu T, Shoji H et al. Neonatal transient eosinophilic colitis causes lower gastrointestinal bleeding in early infancy. J Pediatr Gastroenterol Nutr 2007;44:501–505.
CASE REPORT: SENILE-ONSET AMYLOIDOSIS PRESENTING WITH PAINFUL LOWER EXTREMITY NEUROPATHY To the Editor: Peripheral neuropathy symptomatology ranges from intermittent numbness to constant burning with muscle weakness. Neuropathy interferes with postural control and is a risk factor for falls1 in community-dwelling elderly adults. Identifying the etiology of peripheral neuropathy in elderly adults is challenging because they often have multiple comorbid conditions that may
LETTERS TO THE EDITOR
2017
contribute to the development of this disorder. Pinpointing the cause, such as in senile-onset amyloidosis, whose incidence in elderly adults is unknown and whose prevalence increases with age (seen in 25% of 80-year-olds),2 can help prevent further nerve damage, disability, and falls and help clinicians inform people on their likely prognosis. A high-functioning 73-year-old man presented for an initial geriatric consultation complaining of 12-year progressive lower extremity neuropathic pain accompanied by weakness and imbalance. He had undergone multiple evaluations and was comanaged by staff in a pain clinic using pharmacological and nonpharmacological approaches with the working diagnosis of idiopathic peripheral sensory neuropathy with paresthesias for longer than 5 years. He also complained of dyspnea on exertion for a few months without chest pain or palpitations. His medical history included diabetes mellitus, hypothyroidism, coronary artery disease (CAD), previous myocardial infarction, pacemaker placement, anterior cervical fusion, and bilateral carpal tunnel release in 1998 and 2003. The man was married and employed as a college football coach. He was independent in basic and instrumental activities of daily living. He had a family history of early CAD in his father and brother. On physical examination, his lower extremities had 1+ edema, diminished sensation to monofilament, diminished vibratory sense, dystrophic toenails, palpable pulses, no gross deformity, and intact skin. Cranial nerves were intact, with normal tone, bulk, and strength in his extremities. Reflexes were 1+ except 0 at the Achilles tendon. Romberg was positive. His gait was wide-based and ataxic on tandem walking. His heart rate and rhythm were regular without a third heart sound, and his jugular venous distention was measured at 12 cm. Cognitive testing was normal. Laboratory testing revealed serum protein electrophoresis with no M-protein, a urine protein electrophoresis with trace proteinuria, and free light chains with free kappa of 23.7 and free lambda of 22.6 with a normal K/L ratio. Bone marrow biopsy was negative. Nerve conduction study in 2001 revealed mild demyelination and axonopathy. Subsequent studies, in 2008 and 2012, revealed dramatic progression of a severe sensorimotor axonopathy with demyelinating features and absent lower extremity sensory nerve action potentials (SNAPs). An echocardiogram showed thickening of the left ventricular wall and worsening diastolic filling consistent with restriction. Electrocardiograms revealed low-voltage QRS complexes from 2005 to 2012. He underwent cardiac muscle biopsy, which revealed amorphous eosinophilic deposition that Congo red staining confirmed to be amyloid. Because immunostains for classification of subtypes were unrevealing, further subtype investigation was undertaken with transthyretin (TTR) genetic analysis.
DISCUSSION Amyloidosis results from protein misfolding and deposition within tissues. As a result, neuropathy often presents as a progressive, symmetric, axonal disease of the distal lower extremities with prominent small fiber features, ultimately affecting motor and sensory fibers, decreased SNAPs, and relatively normal conduction velocities.3 The cause of
2018
LETTERS TO THE EDITOR
death is usually from cardiac failure or arrhythmia. Incidence is one in 100,000, with 80% representing amyloidosis-light chain (AL) type, presenting with plasma cell dyscrasias from bone marrow deposition. The remaining cases consist of localized amyloidoses (8%), familial TTR amyloidosis (7%), secondary amyloidosis types (3%), and senile cardiac amyloid (2%). The most common cause of non-AL amyloidosis in elderly adults is due to misfolding of the hepatic protein TTR, a serum transporter of thyroxine and retinol. All TTR variants encoded on chromosome 18 are inherited equally, although men present earlier. Wild-type TTR amyloidosis has an average age of onset of 65.4 Neuropathy causing imbalance may be the presenting symptom to the geriatrician, requiring a fall risk assessment with an investigation into reversible causes. Differentiating between normal and variant-TTR amyloidosis is beneficial if done early in the disease trajectory. Liver transplantation in suitable candidates can remove the main source of variant-TTR production, preventing further deposition. Wild-type TTR producers can have the opportunity to participate in drug trials that may slow progression. In addition to conservative management, clinical trials and cardiac transplantation with or without liver transplantation is recommended before significant disability has been incurred.5–7 During an individual’s second carpal tunnel release, years before cardiac manifestations arise, the transverse ligament can be tested for amyloid in an attempt to find a definitive diagnosis.8,9 Genetic testing for TTR gene mutations can be performed to prevent serious consequences from delayed diagnosis10 and to assist with genetic counseling of family members. A high level of suspicion for a unifying diagnosis of systemic amyloidosis would be prudent for older adults with a history of bilateral carpal tunnel release, pacemaker for conduction abnormalities, and low-voltage QRS complexes on electrocardiogram presenting with imbalance from progressive neuropathy. Diagnosing the cause of the neuropathy can prevent further disability and decrease risk of falls. Carolyn Louisa Kaloostian, MD, MPH Nancy Weintraub, MD Milena Zirovich, MD Department of Veterans Affairs, Greater Los Angeles Healthcare Center, Los Angeles, California
ACKNOWLEDGMENTS Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: All authors: conception, writing, and editing letter. Sponsor’s Role: There was no sponsorship of this work.
REFERENCES 1. Richardson JK, Hurvitz EA. Peripheral neuropathy: A true risk factor for falls. J Gerontol A Biol Sci Med Sci 1995;50A:M211–M215.
OCTOBER 2014–VOL. 62, NO. 10
JAGS
2. Tanskanen M, Peuralinna T, Polvikoski T et al. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: A population-based autopsy study. Ann Med 2008;40:232–239. 3. Matsuda M, Gono T, Morita H et al. Peripheral nerve involvement in primary systemic AL amyloidosis: A clinical and electrophysiological study. Eur J Neurol 2011;18:604–610. 4. Dharmarajan K, Maurer MS. Transthyretin cardiac amyloidoses in older North Americans. J Am Geriatr Soc 2012;60:765–774. 5. Ando Y, Ueda M. Diagnosis and therapeutic approaches to transthyretin amyloidosis. Curr Med Chem 2012;19:2312–2323. 6. Benson DM. Liver transplantation and transthyretin amyloidosis. Muscle Nerve 2013;47:157–162. 7. Erikzon BG, Larsson M, Herlenius G et al. Report from the Familial Amyloidotic Polyneuropathy World Transplant Registry (FAPWTR) and the Domino Liver Transplant Registry (DLTR). Amyloid 2003;1:67–76. 8. M’bappe P, Grateau G. Osteo-articular manifestations of amyloidosis. Best Pract Res Clin Rheumatol 2012;26:459–475. 9. Gioeva Z, Urban P, Meliss RR et al. ATTR amyloid in the carpal tunnel ligament is frequently of wild type transthyretin origin. Amyloid 2013;20:1–6. 10. Plante-Bordeneuve V, Ferreira A, Lalu T et al. Diagnostic pitfalls in sporadic transthyretin familial amyloid polyneuropathy (TTR-FAP). J Neurol 2007;69:693–698.
LEVOFLOXACIN AND SEIZURES: WHAT RISK FOR ELDERLY ADULTS? To the Editor: Fluoroquinolones can trigger seizures by inhibiting the gamma-aminobutyric acid (GABA) binding to the GABAA receptor, especially in individuals with underlying central nervous system (CNS) disease, high CNS penetration of drug, and impaired renal function,1 but this is an unusual adverse effect of levofloxacin. A 93-year-old woman with no past history of seizures or other neurological disorders presented with confusion and dehydration. She was taking no medications, including over-the-counter medications, before the illness, had no known allergies, and did not drink alcohol or use illegal drugs. On admission, the woman appeared dehydrated, disoriented, and unable to answer simple questions; physical examination was otherwise unrevealing. Laboratory findings were normal except for neutrophil leukocytes 11,245/ lL and blood sodium 153 mEq/L; chest X-ray showed pneumonia of the left lower lobe, for which intravenous levofloxacin (500 mg/d) and rehydration were started. Seven hours after infusion of the second dose of levofloxacin, she had relapsing generalized tonic-clonic seizures that were ultimately controlled with diazepam and phenobarbital. Computed tomography of the head without contrast showed no evidence of hemorrhage, masses, or infarction, and electroencephalogram revealed generalized spike-andwave epileptiform discharges. Levofloxacin was stopped, amoxicillin and clavulanate were administered, and no other bouts of seizures occurred over the further course. On the third day, she had multiorgan failure and died. An autopsy was not performed. Levofloxacin is associated with a low rate of clinically important neurological adverse events such as delirium, psychosis, catatonia, headache, dizziness, restlessness, tremor, insomnia, anxiety, depression, and hallucinations.2 Although it is not possible to attribute with absolute certainty the cause of the seizures to levofloxacin in this case, the temporal relationship between the initiation of levo-
Copyright of Journal of the American Geriatrics Society is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
OCTOBER 2014–VOL. 62, NO. 10
Eosinophilic colitis is a rare clinical condition, so the most important factor in making the diagnosis is to have a high degree of clinical suspicion. In conclusion, clinicians should consider EC in the differential diagnosis of LGIB in elderly adults, and early medical treatment should be initiated to avoid serious complications. G€ ulay Kocßak, MD Department of Nephrology, C ß anakkale Onsekiz Mart University, C ß anakkale, Turkey Erdem Kocßak, MD Department of Gastroenterology, C ß anakkale State Hospital, C ß anakkale, Turkey Erdem Akbal, MD Department of Gastroenterology, C ß anakkale Onsekiz Mart University, C ß anakkale, Turkey Hacer Sßen, MD G€ okhan Erba g, MD Ceren Erdo gan, MD Department of Internal Medicine, C ß anakkale Onsekiz Mart University, C ß anakkale, Turkey
ACKNOWLEDGMENTS Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: G€ ulay Kocßak: manuscript concept and design. Erdem Kocßak, G€ okhan Erba g: preparation of manuscript. Erdem Akbal, Hacer Sßen: analysis and interpretation of data. Ceren Erdo gan: subject’s doctor. Sponsor’s Role: No sponsor associated with manuscript.
REFERENCES 1. Chait MM. Lower gastrointestinal bleeding in the elderly. World J Gastrointest Endosc 2010;2:147–154. 2. Alfadda AA, Schaffer EA, Urbanski SJ et al. Eosinophilic colitis is a sporadic self-limited disease of middle-aged people: A population-based study. Colorectal Dis 2014;16:123–129. 3. Yeo SA, Lim YK, Lim KH et al. Toxic haemorrhagic colitis: A rare presentation of eosinophilic colitis. Case Rep Gastrointest Med 2012;2012: 279813. 4. Ohtsuka Y, Shimizu T, Shoji H et al. Neonatal transient eosinophilic colitis causes lower gastrointestinal bleeding in early infancy. J Pediatr Gastroenterol Nutr 2007;44:501–505.
CASE REPORT: SENILE-ONSET AMYLOIDOSIS PRESENTING WITH PAINFUL LOWER EXTREMITY NEUROPATHY To the Editor: Peripheral neuropathy symptomatology ranges from intermittent numbness to constant burning with muscle weakness. Neuropathy interferes with postural control and is a risk factor for falls1 in community-dwelling elderly adults. Identifying the etiology of peripheral neuropathy in elderly adults is challenging because they often have multiple comorbid conditions that may
LETTERS TO THE EDITOR
2017
contribute to the development of this disorder. Pinpointing the cause, such as in senile-onset amyloidosis, whose incidence in elderly adults is unknown and whose prevalence increases with age (seen in 25% of 80-year-olds),2 can help prevent further nerve damage, disability, and falls and help clinicians inform people on their likely prognosis. A high-functioning 73-year-old man presented for an initial geriatric consultation complaining of 12-year progressive lower extremity neuropathic pain accompanied by weakness and imbalance. He had undergone multiple evaluations and was comanaged by staff in a pain clinic using pharmacological and nonpharmacological approaches with the working diagnosis of idiopathic peripheral sensory neuropathy with paresthesias for longer than 5 years. He also complained of dyspnea on exertion for a few months without chest pain or palpitations. His medical history included diabetes mellitus, hypothyroidism, coronary artery disease (CAD), previous myocardial infarction, pacemaker placement, anterior cervical fusion, and bilateral carpal tunnel release in 1998 and 2003. The man was married and employed as a college football coach. He was independent in basic and instrumental activities of daily living. He had a family history of early CAD in his father and brother. On physical examination, his lower extremities had 1+ edema, diminished sensation to monofilament, diminished vibratory sense, dystrophic toenails, palpable pulses, no gross deformity, and intact skin. Cranial nerves were intact, with normal tone, bulk, and strength in his extremities. Reflexes were 1+ except 0 at the Achilles tendon. Romberg was positive. His gait was wide-based and ataxic on tandem walking. His heart rate and rhythm were regular without a third heart sound, and his jugular venous distention was measured at 12 cm. Cognitive testing was normal. Laboratory testing revealed serum protein electrophoresis with no M-protein, a urine protein electrophoresis with trace proteinuria, and free light chains with free kappa of 23.7 and free lambda of 22.6 with a normal K/L ratio. Bone marrow biopsy was negative. Nerve conduction study in 2001 revealed mild demyelination and axonopathy. Subsequent studies, in 2008 and 2012, revealed dramatic progression of a severe sensorimotor axonopathy with demyelinating features and absent lower extremity sensory nerve action potentials (SNAPs). An echocardiogram showed thickening of the left ventricular wall and worsening diastolic filling consistent with restriction. Electrocardiograms revealed low-voltage QRS complexes from 2005 to 2012. He underwent cardiac muscle biopsy, which revealed amorphous eosinophilic deposition that Congo red staining confirmed to be amyloid. Because immunostains for classification of subtypes were unrevealing, further subtype investigation was undertaken with transthyretin (TTR) genetic analysis.
DISCUSSION Amyloidosis results from protein misfolding and deposition within tissues. As a result, neuropathy often presents as a progressive, symmetric, axonal disease of the distal lower extremities with prominent small fiber features, ultimately affecting motor and sensory fibers, decreased SNAPs, and relatively normal conduction velocities.3 The cause of
2018
LETTERS TO THE EDITOR
death is usually from cardiac failure or arrhythmia. Incidence is one in 100,000, with 80% representing amyloidosis-light chain (AL) type, presenting with plasma cell dyscrasias from bone marrow deposition. The remaining cases consist of localized amyloidoses (8%), familial TTR amyloidosis (7%), secondary amyloidosis types (3%), and senile cardiac amyloid (2%). The most common cause of non-AL amyloidosis in elderly adults is due to misfolding of the hepatic protein TTR, a serum transporter of thyroxine and retinol. All TTR variants encoded on chromosome 18 are inherited equally, although men present earlier. Wild-type TTR amyloidosis has an average age of onset of 65.4 Neuropathy causing imbalance may be the presenting symptom to the geriatrician, requiring a fall risk assessment with an investigation into reversible causes. Differentiating between normal and variant-TTR amyloidosis is beneficial if done early in the disease trajectory. Liver transplantation in suitable candidates can remove the main source of variant-TTR production, preventing further deposition. Wild-type TTR producers can have the opportunity to participate in drug trials that may slow progression. In addition to conservative management, clinical trials and cardiac transplantation with or without liver transplantation is recommended before significant disability has been incurred.5–7 During an individual’s second carpal tunnel release, years before cardiac manifestations arise, the transverse ligament can be tested for amyloid in an attempt to find a definitive diagnosis.8,9 Genetic testing for TTR gene mutations can be performed to prevent serious consequences from delayed diagnosis10 and to assist with genetic counseling of family members. A high level of suspicion for a unifying diagnosis of systemic amyloidosis would be prudent for older adults with a history of bilateral carpal tunnel release, pacemaker for conduction abnormalities, and low-voltage QRS complexes on electrocardiogram presenting with imbalance from progressive neuropathy. Diagnosing the cause of the neuropathy can prevent further disability and decrease risk of falls. Carolyn Louisa Kaloostian, MD, MPH Nancy Weintraub, MD Milena Zirovich, MD Department of Veterans Affairs, Greater Los Angeles Healthcare Center, Los Angeles, California
ACKNOWLEDGMENTS Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: All authors: conception, writing, and editing letter. Sponsor’s Role: There was no sponsorship of this work.
REFERENCES 1. Richardson JK, Hurvitz EA. Peripheral neuropathy: A true risk factor for falls. J Gerontol A Biol Sci Med Sci 1995;50A:M211–M215.
OCTOBER 2014–VOL. 62, NO. 10
JAGS
2. Tanskanen M, Peuralinna T, Polvikoski T et al. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: A population-based autopsy study. Ann Med 2008;40:232–239. 3. Matsuda M, Gono T, Morita H et al. Peripheral nerve involvement in primary systemic AL amyloidosis: A clinical and electrophysiological study. Eur J Neurol 2011;18:604–610. 4. Dharmarajan K, Maurer MS. Transthyretin cardiac amyloidoses in older North Americans. J Am Geriatr Soc 2012;60:765–774. 5. Ando Y, Ueda M. Diagnosis and therapeutic approaches to transthyretin amyloidosis. Curr Med Chem 2012;19:2312–2323. 6. Benson DM. Liver transplantation and transthyretin amyloidosis. Muscle Nerve 2013;47:157–162. 7. Erikzon BG, Larsson M, Herlenius G et al. Report from the Familial Amyloidotic Polyneuropathy World Transplant Registry (FAPWTR) and the Domino Liver Transplant Registry (DLTR). Amyloid 2003;1:67–76. 8. M’bappe P, Grateau G. Osteo-articular manifestations of amyloidosis. Best Pract Res Clin Rheumatol 2012;26:459–475. 9. Gioeva Z, Urban P, Meliss RR et al. ATTR amyloid in the carpal tunnel ligament is frequently of wild type transthyretin origin. Amyloid 2013;20:1–6. 10. Plante-Bordeneuve V, Ferreira A, Lalu T et al. Diagnostic pitfalls in sporadic transthyretin familial amyloid polyneuropathy (TTR-FAP). J Neurol 2007;69:693–698.
LEVOFLOXACIN AND SEIZURES: WHAT RISK FOR ELDERLY ADULTS? To the Editor: Fluoroquinolones can trigger seizures by inhibiting the gamma-aminobutyric acid (GABA) binding to the GABAA receptor, especially in individuals with underlying central nervous system (CNS) disease, high CNS penetration of drug, and impaired renal function,1 but this is an unusual adverse effect of levofloxacin. A 93-year-old woman with no past history of seizures or other neurological disorders presented with confusion and dehydration. She was taking no medications, including over-the-counter medications, before the illness, had no known allergies, and did not drink alcohol or use illegal drugs. On admission, the woman appeared dehydrated, disoriented, and unable to answer simple questions; physical examination was otherwise unrevealing. Laboratory findings were normal except for neutrophil leukocytes 11,245/ lL and blood sodium 153 mEq/L; chest X-ray showed pneumonia of the left lower lobe, for which intravenous levofloxacin (500 mg/d) and rehydration were started. Seven hours after infusion of the second dose of levofloxacin, she had relapsing generalized tonic-clonic seizures that were ultimately controlled with diazepam and phenobarbital. Computed tomography of the head without contrast showed no evidence of hemorrhage, masses, or infarction, and electroencephalogram revealed generalized spike-andwave epileptiform discharges. Levofloxacin was stopped, amoxicillin and clavulanate were administered, and no other bouts of seizures occurred over the further course. On the third day, she had multiorgan failure and died. An autopsy was not performed. Levofloxacin is associated with a low rate of clinically important neurological adverse events such as delirium, psychosis, catatonia, headache, dizziness, restlessness, tremor, insomnia, anxiety, depression, and hallucinations.2 Although it is not possible to attribute with absolute certainty the cause of the seizures to levofloxacin in this case, the temporal relationship between the initiation of levo-
Copyright of Journal of the American Geriatrics Society is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
