A 36‐year‐old man with paresthesias and a headache

Abstract

History of the present illnessA 36-year-old man with a history of non-Hodgkin's lymphoma was admitted to the hospital with paresthesias and a headache. His paresthesias began 5 months prior to admission, when he developed left leg numbness and pain, accompanied by an erythematous rash that he described as "splotchy." The rash appeared initially on the patient's left leg, but then expanded to include his torso and upper extremities. The rash, numbness, and pain all resolved without intervention after 1 week. Three months prior to admission, he experienced recurrent numbness in the left leg that again resolved spontaneously after several days.Two months prior to admission, the patient's symptoms intensified. He developed bilateral numbness and tingling, first in both feet and then in both hands. He noted that grasping objects with his hands caused a burning sensation in his palms, and he experienced pain and swelling in his left foot and ankle. After these symptoms had been present for several weeks, the patient established care with a primary care physician. At his first appointment his erythrocyte sedimentation rate (ESR) was 42 mm/hour (normal range 1-20). An assay for antinuclear antibodies (ANA) was positive at a titer of 1:160 (speckled), but antibodies to double-stranded DNA and to extractable nuclear antigens (Ro, La, Sm, and RNP) were negative. The laboratory results are shown in Table 1.One month before admission, the patient developed "unbearable" pain in his feet and noted that his socks felt too tight. He reported tingling in his hands, nausea, and daily emesis. The patient was referred for nerve conduction velocity and electromyography of the lower and upper extremities. These investigations revealed a symmetric sensory polyneuropathy that predominantly involved the lower extremities. The patient was prescribed gabapentin (200 mg 3 times daily), but his symptoms persisted. Three days prior to admission, the patient developed a severe occipital headache that did not remit despite use of ibuprofen (600 mg 3 times daily).On the morning of admission, the patient presented to his primary care doctor reporting a severe headache (rated as 10/10), profound fatigue, and numbness, pain, and weakness in both feet. His blood pressure was 168/119 mm Hg in the right arm and 175/123 mm Hg in the left arm. He was referred to the emergency department for hypertensive urgency. Past medical historyThe patient's non-Hodgkin's lymphoma was diagnosed at age 16 years. He had been treated with a standard chemotherapy regimen for 6 cycles (CHOP: cyclophosphamide, hydroxydaunomycin [doxorubicin], vincristine, and prednisone). This treatment was presumed to have resulted in a cure. The patient was also diagnosed with iron deficiency anemia several years before admission. An esophagogastroduodenoscopy at that time was normal. Family and social historyThe patient's family history was remarkable for the fact that his father had multiple strokes before the age of 40 years. In addition, the patient reported many relatives on both p...

Antifibrotic effect of lysophosphatidic acid receptors LPA1 and LPA3 antagonist on experimental murine scleroderma induced by bleomycin

“…In vitro studies using fibroblasts derived from either Smad2-or 3-null embryos have revealed a complex picture of TGF-b1 transcriptional regulation, indicating distinct mechanisms of TGF-b1 gene regulation by Smad2, Smad3 or both (19). Castelino et al (11) demonstrated a pathological role of LPA 1 receptor in dermal fibrosis. Using a scleroderma model, Castelino reported a reduction in dermal fibrosis, a-SMA-positive cells and phospho-Smad2-positive cells in LPA 1 knockout mice.…”

“…LPA levels were elevated in serum of SSc compared with serum of healthy controls (9), and fibroblasts cultured from SSc skin showed a significant increase of LPA-activated chloride channel current activity following LPA exposure compared with control skin fibroblasts (10). Also, the role of LPA has been demonstrated in several animal models of organ fibrosis (11)(12)(13)(14)(15). In a renal fibrosis model using unilateral ureteral obstruction, tubulointerstitial fibrosis was reduced in LPA 1 receptor knockout mice (14).…”