Diarrhea is one of the most common symptoms in common variable immunodeficiency, but neurologic manifestations are rare. We presented a 50-year-old woman with recurrent diarrhea and severe weight loss that developed a posterior cord syndrome. Endoscopy found a duodenal villous blunting, intraepithelial lymphocytosis, and lack of plasma cells and magnetic resonance imaging of the spine was normal. Laboratory assays confirmed common variable immunodeficiency syndrome and showed low levels of trace elements (copper and zinc). Treatment was initiated with parenteral replacement of trace elements and intravenous human immunoglobulin and the patient improved clinically. In conclusion, physicians must be aware that gastrointestinal and neurologic disorders may be related to each other and remember to request trace elements laboratory assessment.
Common variable immunodeficiency (CVID) is the most common primary immunodeficiency in clinical practice, with an incidence of 1/10,000 to 1/50,000 [
Diarrhea is one the most common symptoms in CVID and can be caused by a myriad of diseases. Recurrent infections and intestinal wall inflammatory dysfunction are two usual etiologies of diarrhea. On the other hand, neurological manifestations in CVID are rare. Among neurologic diseases, meningitis due to encapsulated bacteria is relatively common. However, transverse myelitis, peroneal muscular atrophy, Guillain-Barré syndrome, and myasthenia gravis were also reported.
Gastrointestinal and neurologic disorders may be related to each other. Cobalamin deficiency may occur because of intestinal malabsorption, causing anemia and neurologic disorders such as cognitive dysfunction, posterior spinal cord syndrome, and/or peripheral neuropathy. In addition, malabsorption of other vitamins and trace elements may also cause neurologic disease. However, among previous reports of trace elements deficiency in CVID none manifested as neurologic disease. We report the case of a 50-year-old woman with CVID and chronic diarrhea whose neurologic manifestations were due to intestinal malabsorption of trace elements.
A 50-year-old Brazilian white woman presented to an outpatient clinic with a history of frequent episodes of diarrhea over the last three years, with presence of food debris, postprandial fullness, and significant weight loss. Patient denied fever, blood, or mucus in stool. Physical examination was normal. Patient underwent stool examination and upper and lower gastrointestinal (GI) endoscopy that were normal. In addition, antiendomysial gliadin and transglutaminase antibodies were also negative. Treatment with probiotics and a gluten-free diet was ineffective.
Over the next months she developed asthenia, paraesthesia, and infrapatellar edema in the lower limbs. A new neurologic examination showed positive Romberg sign, ataxic gait, and loss of balance and patient was admitted to our institution. Admission laboratorial exams demonstrated anemia and electrolyte imbalance (Table
Laboratorial exams.
Exams | Day 0 | Day 10 | Day 14 | Day 21 |
---|---|---|---|---|
Hb (g/L) | 126 | 94 | 95 | 93 |
HCT (%) | 39.9 | 32.8 | 33.2 | 30.7 |
VCM (fL) | 73 | 74 | ||
Leucocytes (cel/mm3) | 16,310 | 8,800 | 8,400 | 7,200 |
Platelets (platelets/mm3) | 572.000 | 415.000 | 367.000 | 282.000 |
CRP (mg/dL) | 3.59 | 0.19 | 3.00 | |
Glucose (mmol/dL) | 4.77 | 4.22 | 4.66 | 4.66 |
Urea (mmol/dL) | 11.78 | 6.43 | 2.86 | 7.50 |
Creatinine ( |
7.07 | 4.42 | 4.42 | 5.30 |
Na (mmol/L) | 142 | 141 | 141 | 141 |
K (mmol/L) | 3.0 | 3.3 | 4.5 | 3.7 |
Mg (mmol/L) | 0.4 | 1.0 | 0.65 | |
Ca (mmol/L) | 2.08 | 2.15 | ||
AST ( |
0.42 | 0.73 | 0.95 | |
ALT ( |
0.92 | 1.39 | 1.75 | |
Serum protein (g/L) | 58 | 43 | 45 | 43 |
Albumin (g/L) | 37 | 23 | 25 | 23 |
Cobalamin (pmol/mL) | 379.9 | |||
Folic acid (nmol/L) | 7.6 | |||
Copper ( |
3.61 | |||
Zinc ( |
52 | |||
Aluminum ( |
2 | |||
Iron ( |
41 | |||
Ferritin (ng/mL) | 104 |
ALT: alanine aminotransferase; AST: aspartate aminotransferase; Ca: calcium; CRP: c-reactive protein; Hb: hemoglobin; HTO: hematocrit; K: potassium; Mg: magnesium; and Na: sodium.
Serum immunoglobulins assays.
Parameter | Value |
---|---|
IgA (mg/dL) | <6.6 |
IgG (mg/dL) | 232.0 |
IgM (mg/dL) | 9.5 |
IgA: immunoglobulin A; IgG: immunoglobulin G; and IgM: immunoglobulin M.
(a) Duodenal villous blunting, HE stain, 10x. (b) Duodenal villous blunting, oedema, HE stain, 10x. (c) Intraepithelial lymphocytosis and lack of plasma cells, HE stain, 10x. (d) Immunohistochemistry CD3-T lymphocytes positive. (e) Immunohistochemistry MUM 1 plasma cells negative.
Sagittal and axial T2 weighted MRI images. Vertebral height, disc height, alignment, and bone marrow signal are within normal limits. The canal and neural exit foramina are capacious at all levels.
We describe the case of a previously healthy patient with chronic diarrhea and significant weight loss associated with symptoms of posterior spinal cord syndrome. CVID comprises a heterogeneous group of diseases characterized by abnormal antibody production. It affects men and women equally and the clinical manifestations may begin at any age [
Recurrent infections are CVID most common clinical manifestation. These infections usually occur at respiratory and gastrointestinal tract. Beside recurrence, atypical pathogens and more severe course are key points to diagnosis. Bacterial infections by encapsulated organism, such as
Over 60% of patients with CVID have digestive disorders [
An increasing awareness of neurologic problems in common variable immunodeficiency has been reported, despite lack of data about its incidence. In the series of Webster, meningitis was described as the most common neurologic manifestation [
A high prevalence of autoimmune manifestations characterizes common variable immunodeficiency [
Posterior cord syndrome is a condition caused by lesion of the posterior portion of the spinal cord, responsible for proprioceptive sensibility. Main signs and symptoms are loss of proprioception and vibration sensation, ataxic gait, positive Romberg sign, hypotonia, and abolition of deep tendon reflexes. Our patient developed most of these symptoms. Posterior cord syndrome can be caused by systemic diseases, such as syphilis and deficiency of cobalamin and trace elements, such as copper, zinc, and aluminum. In a series of 13 cases of CVID, Agarwal et al. observed reduced serum zinc levels in most patients [
Common variable immunodeficiency is a big challenge for doctors in primary care centers. The myriad of clinical symptoms and associated disorders can cause delays in diagnosis and treatment. In this case we highlighted the association of gastrointestinal and neurologic disease due to trace elements deficiency. Studies of trace elements malabsorption in CVID are much desirable. Moreover, physicians must be aware that gastrointestinal and neurologic disorders may be related to each other and remember to request trace elements laboratory assessment.
The authors declared that there is no conflict of interests regarding the publication of this paper.
All authors have participated significantly in writing this paper and approving its content.