A 46‐year‐old woman with chin pain and a fainting spell

Abstract

A 46-year-old woman presented with chin pain and a fainting spell. The patient had a history of primary central nervous system (CNS) lymphoma that had recurred in the past but had been in remission for 2 years. She was admitted to the hospital in August 2008, following a syncopal episode. For several weeks prior to her syncope, she had experienced generalized malaise and the sensation of total body weakness. On the day of admission, she was nauseated and had one episode of non-bloody emesis. As the day progressed, she felt lightheaded and eventually lost consciousness while walking to the bathroom. In the emergency department, she was suspected of dehydration. However, an electrocardiogram revealed complete heart block (CHB). A temporary transjugular pacing wire was placed, intravenous fluids were started, and she was admitted to the Cardiac Unit. The patient stated that she had been completely well until 2 months before admission, when she began to experience easy fatigability. One month before admission, she developed a series of episodes of myalgias that involved her shoulders and neck. These symptoms responded to acetaminophen. She had also experienced periodic night sweats during this time. Two weeks before admission, the patient presented to her oncologist with the symptom of chin pain that radiated bilaterally toward the angle of her mandible. The pain was described as “sharp and shooting.” It sometimes appeared to be worsened by jaw movement. The patient indicated that chewing exacerbated the pain, starting with the first bite. Her oncologist had obtained a brain magnetic resonance imaging (MRI) study to exclude a lymphoma recurrence. The MRI study was interpreted as showing no new lesions. The pain did not respond to nonsteroidal antiinflammatory drugs and had been present for 2 weeks at the time of her syncope. The patient had a history of diffuse large non-Hodgkin's B cell CNS lymphoma. This had been diagnosed 10 years before admission and treated with chemotherapeutic doses of methotrexate (MTX), and was followed by maintenance MTX infusions. She had achieved a complete remission for 4 years on this regimen. Six years before admission, the patient had experienced a recurrence of her CNS lymphoma, manifested by cognitive changes and accompanied by radiologic evidence of new lesions on a brain MRI scan. She resumed therapy with MTX, which continued through 2004. In 2005, she developed new brain lesions that were treated with the combination of high-dose MTX, rituximab, and temozolomide. This regimen induced another complete remission, but she experienced a third recurrence in 2006, at which time she was treated with myeloablative chemotherapy consisting of cytarabine (Ara-C)/etoposide (VP-16), followed by autologous bone marrow rescue. Following her bone marrow transplant, she had remained in remission until the time of the current presentation. Aside from her oncologic history, the only other past medical history of note was a caesarean section delivery performed in early 2002, followed by a hysterectomy for placenta previa. The patient's medications were ibuprofen (600 mg) or acetaminophen (1,000 mg) as needed for pain. She reported gastrointestinal intolerance to narcotics, including both morphine sulfate and oxycodone. The patient's family history was remarkable for throat cancer in a paternal uncle. She had no family history of coronary artery disease, arrhythmia, diabetes mellitus, or autoimmune disease. The patient was originally from Brazil but had lived in the US for 20 years. She was married and lived with her husband and 6-year-old son. She worked as a house cleaner, denied tobacco and illicit drug use, and rarely used alcohol. The patient reported malaise and night sweats for 2 months before admission. She noted that the chin and jaw pain had been present for 2 weeks. She also recalled a red, round rash on her inner thigh several months earlier that had resolved on its own. She denied fevers, chills, weight loss, chest pain, palpitations, dyspnea, and abdominal symptoms. She also denied headaches, visual changes, arthralgias, oral ulcers, recent dental work, or scalp tenderness. She had no sick contacts or recent travel. Upon arrival in the Cardiac Unit, her temperature was 98.2°F, her pulse was 60 beats/minute, her blood pressure was 112/60 mm Hg, and her respiratory rate and room air oxygen saturation were 16 breaths/minute and 98%, respectively. She appeared comfortable lying in bed. Her mucous membranes were moist and the conjunctivae were not injected. She had no oral lesions. She had easily palpable, nontender temporal arteries. No lymphadenopathy was appreciated at the cervical, supraclavicular, axillary, abdominal, or inguinal sites. Her neck was supple, and inspection revealed a right-sided internal jugular venous-access catheter. The lung fields were clear to auscultation. Her cardiac examination was notable for a paced rhythm of 60 beats/minute without murmurs, rubs, or gallops. There were no subclavian or carotid bruits. The abdominal examination showed no organomegaly and a soft, nontender abdomen. She had no clubbing, cyanosis, or edema on any extremity. The fingers were without tapering or dilatation of her nailbed capillaries, and her peripheral pulses were full and symmetric throughout. There was no rash. The neurologic examination revealed a patient who was awake, alert, and oriented. The extraocular movements were full and the visual fields were intact. Cranial nerve V was intact in all 3 distributions, as were cranial nerves VII–XII. There was normal bulk, tone, and power of the muscles, and the sensory examination was intact to light touch, pinprick, and vibration. The deep tendon reflexes were 2+ and symmetric, and the plantar responses were flexor. The patient's speech was normal. Initial laboratory investigations are shown in Table 1. The patient's white blood cell count and platelet count were normal and her hematocrit was at its baseline (30.6%; normal range 36.0–46.0%). Her serum chemistries were unremarkable, and cardiac biomarkers were normal. The erythrocyte sedimentation rate was 95 mm/hour (normal value ≤17), and her C-reactive protein level was 15.2 mg/liter (normal value <8.0). A diagnostic test was performed. The patient is a 46-year-old woman with a history of a recurrent CNS lymphoma who has experienced several weeks of malaise and jaw pain. She is admitted now after a syncopal episode. She has elevated inflammatory markers and is in CHB. The Rheumatology Service was consulted regarding the question of possible giant cell arteritis (GCA). We will discuss the differential diagnosis of this patient's jaw pain, review certain important points about the assessment of a patient with new heart block, and consider diagnoses that might link these two features of the patient's presentation. The admitting medical team was concerned about GCA as the possible cause for our patient's jaw symptoms and elevated inflammatory markers. Classic GCA symptoms include headache, polymyalgia rheumatica, scalp tenderness, vision disturbances (e.g., anterior ischemic optic neuropathy with vision loss), and jaw claudication (1). Jaw claudication, which our patient's radiating chin pain might have represented, is the most specific of all GCA symptoms for that diagnosis (2). In GCA, the jaw pain is caused by claudication of the muscles of mastication, such as the masseter. Pain usually starts within seconds once the patient begins to chew. The action of chewing becomes intolerable, and the symptom subsides with the cessation of chewing. Upon close questioning, it became clear that our patient's jaw pain was distinctly different from jaw claudication. The timing, quality, and location of her pain were more consistent with a neurogenic than a vascular etiology. Moreover, GCA is exceedingly rare among individuals age <50 years. In a study of more than 1,435 patients who had temporal artery biopsy results positive for temporal arteritis, only 2 (0.14%) were age <50 years (3). Thus, from the start, GCA was unlikely to be the explanation for the patient's symptoms and findings. The patient's sharp, stabbing chin pain was most consistent with pathology in the mental nerve, a branch of the mandibular division of the trigeminal nerve. Mental neuropathy, or the “numb chin syndrome,” is manifested by sensory dysfunction (pain, paresthesia, dysesthesia, hypoesthesia, or anesthesia) in the territory of the mental nerve. The mental nerve is a pure sensory nerve. Thus, mental neuropathy has no motor manifestations. The causes of mental neuropathy are classified into systemic and local etiologies. The most common systemic causes of mental neuropathy are neoplastic in nature. In metastatic cancers, particularly hematologic malignancies, both the initial disease manifestation and the first sign of a recurrence can be symptoms of a mental neuropathy. Cancers can cause mental neuropathies via several mechanisms, including invasion of the mandibular canal or mental foramen by mandibular metastases, or a mandibular focus of a hematologic malignancy (4, 5). In addition, skull base metastases, leptomeningeal invasion, or paraneoplastic syndromes can also lead to mental neuropathy (6). Non-Hodgkin's lymphoma, Burkitt's lymphoma, multiple myeloma, breast cancer, lung cancer, and prostate cancer are the malignancies most commonly reported as causes of a mental neuropathy (6). In view of our patient's history of recurrent CNS lymphoma, our immediate concern was for a recurrence of her lymphoma, possibly with leptomeningeal spread. The normal brain MRI result several weeks earlier did not exclude this possibility. Local oropharyngeal tumors, either malignant or benign, can also cause mental nerve compression. Examples include neuroma, schwannoma, neurofibroma, and mandibular sarcomas. There are case reports of cranial neuropathies associated with GCA, but this remains rare (7, 8). Iatrogenic neuropathies account for most local causes of a mental neuropathy. These include nerve injury from molar extractions, implant insertions near the mental foramen, mandibular surgery, or other dental prostheses. Other non-neoplastic local factors to consider are traumatic fractures, oropharyngeal infections, and mandibular atrophy associated with aging. Our patient had had no recent dental manipulations and denied trauma. Miscellaneous other conditions, including Lyme disease and multiple sclerosis, can also lead to mental neuropathy, although not their usual cranial manifestations (9, 10). These are shown in Table 2. The differential diagnosis of heart block is also shown in Table 2. The 2 most common causes of atrioventricular (AV) block are fibrosis/sclerosis of the conduction system and ischemic heart disease (11). The individuals affected most often by these conditions are the elderly or those with coronary artery disease or its associated risk factors. Our patient did not fit these categories. Certain medications are also prone to cause varying degrees of heart block. For example, digoxin, calcium-channel blockers, amiodarone, adenosine, and beta-blockers achieve some of their therapeutic effects through inhibition of the AV node. Excessive doses of these medications or their administration to patients whose AV node is compromised in other ways can lead to CHB. Infiltrative diseases such as sarcoidosis, amyloidosis, and hemochromatosis, as well as collagen vascular diseases, including systemic lupus erythematosus, dermatomyositis, systemic sclerosis, ankylosing spondylitis, and rheumatoid arthritis, occasionally present with heart block (12). These diseases generally have other obvious symptoms or signs at the time heart block presents. The children of mothers who have anti-Ro antibodies can develop defects in the cardiac conduction system. Although such problems usually present in utero, patients as old as 37 years have been reported (13). At age 46 years, the chance of a complication of maternal anti-Ro antibodies was extremely remote. Given the abrupt onset of her heart block and our patient's medical history, we were concerned about either an infection or an infiltrative malignancy as the etiology of her CHB. Rheumatic fever, viral infections, diphtheria, toxoplasmosis, bacterial endocarditis, syphilis, and other infectious causes can lead to the development of an AV block. The fact that our patient resided in New England made Lyme carditis a possibility. Lyme carditis causes acute AV block in otherwise healthy patients (14). This complication is usually resolved promptly following the start of appropriate antibiotic therapy (15). Temporary pacing is seldom required. The most appealing way to tie together this patient's presentation was the diagnosis of Lyme disease. In this setting, a Western blot analysis of the patient's serum should be diagnostic of an acute infection with Borrelia burgdorferi. If such serologies were negative, then additional scrutiny for recurrent CNS lymphoma would be mandatory. The patient was treated with intravenous ceftriaxone 2 gm once daily on admission for the possibility of Lyme myocarditis. She was also treated empirically with prednisone 40 mg/day for the first 2 days of her hospitalization, because of the concern for possible GCA. The systemic glucocorticoids were stopped after the suspicion for GCA became lower. On hospital day 3, serologies to B burgdorferi returned with positive bands for both IgG (p18, p28, p39, p41, p66) and IgM (p23, p39, p41) on Western blot analysis, which was reflexively done after a positive enzyme-linked immunosorbent assay. The patient's symptoms all gradually improved, and by the third hospital day she was no longer requiring the cardiac pacemaker. She was discharged to complete a 21-day course of oral doxycycline for treatment of her Lyme carditis and neuropathy. She had complete resolution of her heart block and jaw pain and had experienced no recurrence of either at the time of the 6-month followup. This case demonstrates a common scenario encountered in clinical rheumatology, specifically the appearance of pathologic findings in several organ systems with close temporal relationships, and the challenge to determine their systemic relationship, if any. The differential diagnosis in such cases often revolves around the same 3 broad categories of disease: inflammatory, oncologic, and infectious. With our patient, the leading 3 diagnoses were GCA, recurrent CNS lymphoma, and Lyme disease. Among these 3 disorders, only Lyme disease explained both the chin pain syndrome and her new-onset heart block, thereby hewing the fine line of Occam's razor (16). Lyme carditis is estimated to occur in 4–10% of untreated patients with Lyme disease in the US (17, 18). It occurs most often during stage 2 of the B burgdorferi infection, the early disseminated stage, accompanied by neurologic symptoms and musculoskeletal symptoms. The early disseminated stage usually develops weeks to months after the appearance of an erythema migrans lesion (14). Our patient indicated that she had an erythematous rash on her thigh several months before these symptoms, and this most likely represented an erythema migrans lesion. The principal manifestation of Lyme carditis is a self-limited conduction defect, usually consisting of variable degrees of AV conduction delay. Carditis can lead to lightheadedness, syncope, dyspnea, palpitations, and chest pain, but it can also be asymptomatic, a fact that probably contributes to an underestimation of this complication's true prevalence. B burgdorferi infections have also been reported to cause pericarditis, endocarditis, myocarditis, pericardial effusion, myocardial infarction, coronary artery aneurysm, prolonged QT interval, and congestive heart failure. The conduction abnormalities are generally limited, with CHB resolving by an average of one week and lesser degrees of block by one month. Temporary pacemakers are required in a minority of cases. The need for permanent pacing despite antibiotics is quite rare. Lyme disease remains a clinical diagnosis. In the absence of a classic erythema migrans rash, few findings are specific for Lyme disease, and clues are obtained by a careful history, including possible tick exposure risk factors. There has been interest in noninvasive imaging to aid in the diagnosis of Lyme carditis, specifically with cardiac MRI. Although echocardiography generally reveals a normal ejection fraction and no other pathologic findings, there are reports of late enhancement of the epimyocardium after gadolinium administration during cardiac MRI after acute Lyme carditis (19). Some case reports indicate persistence of the gadolinium enhancement at 4 months even in the absence of symptoms (19), whereas others have observed resolution of the findings (20). Transvenous endomyocardial biopsy of patients with Lyme carditis has revealed band-like infiltrates that are considered strongly indicative of this condition, but the invasive nature of this procedure and its uncertain sensitivity and specificity have limited its utility in clinical practice (21, 22). A recent case series of pediatric patients with early disseminated Lyme disease sought to identify predictive factors for the development of Lyme carditis (23). The authors found that older age, arthralgias, and any cardiopulmonary symptoms at onset made the development of Lyme carditis more likely. Conversely, the presence of a cranial neuropathy made Lyme carditis less likely. Although no comparable study has been performed in adults, these findings are consistent with the teaching that the co-occurrence of Lyme disease–associated cranial neuropathy and carditis is unusual. Borrelia burgdorferi infection complicated by mental neuropathy and complete heart block. All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication. Dr. Emkey had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design. Emkey, Stone. Acquisition of data. Emkey, Stone. Analysis and interpretation of data. Emkey, Stone.