Rural health challenges in Western Uganda: pernicious anemia masquerading as recurrent lower limb weakness—a case report

Abstract

Background

Pernicious anemia, also called Biemer’s disease, is an autoimmune disease and the most common cause of cobalamin deficiency globally. Various genetic, environmental, and immunological factors interplay to lead to its presentation. Pernicious anemia has a myriad of presentations, which can range from hematological and skin-related to neurological. Pernicious anemia has been reported among people of all ages worldwide, especially those over 60 years old. Its prevalence in the general population is about 0.1% and 1.9% for elderly patients over 60 years old. Like most other autoimmune diseases, females are more affected than males. However, there are case reports of pernicious anemia occurring in individuals at 40 years of age. The prevalence of pernicious anemia in Africa has been reportedly low, possibly owing to underdiagnosis.

Case presentation

This case identifies a 51-year-old Ugandan man from the tribe of Ankole who presented with lower limb weakness for about 2 months. He had a similar presentation 7 years prior for which he was treated for vitamin B12 deficiency. Initial blood counts revealed macrocytic anemia. Considering the recurrence of symptoms, serum cobalamin levels and serum intrinsic factor autoantibodies were tested and the diagnosis of pernicious anemia was confirmed. The patient improved on parenteral methylcobalamin therapy.

Conclusion

This case report highlights the importance of a high index of suspicion in early diagnosis of vitamin B12 deficiency as a cause of neurological symptoms and in considering the diagnosis and empiric therapy for pernicious anemia in a resource-limited context.

Background

Pernicious anemia, also called Biemer’s disease, is an autoimmune disease and the most common cause of cobalamin deficiency globally. Various genetic, environmental, and immunological factors interplay to lead to its presentation. It may co-occur with autoimmune conditions such as thyroid diseases, insulin-dependent diabetes mellitus, polyendocrinopathy, and vitiligo [1,2,3]. Pernicious anemia has a myriad of presentations that can range from hematological and skin-related to neurological [4]. Affected patients may present with symptoms of anemia such as palpitations, lethargy, dizziness, headache, and later neurological symptoms such as paresthesia, imbalance, dementia, psychosis, personality changes, and skin hyperpigmentation [1, 3]. Pernicious anemia (PA) has been reported among people of all ages worldwide, especially those over 60 years old [2, 3]. Its prevalence in the general population is about 0.1% and 1.9% for elderly patients over 60 years. The exact prevalence of PA in Africa is not known. Like most other autoimmune diseases, females are more affected than males. However, there are case reports of PA occurring in individuals at 40 years of age [5,6,7]. Here, we report the case of a 51-year-old man who presented with recurrent lower limb weakness and was later diagnosed with pernicious anemia in a resource-limited rural setting in Western Uganda.

Case presentation

A 51-year-old Ugandan man from the tribe of Ankole who had no documented chronic illness visited an outpatient department at Kampala International University-Teaching Hospital (KIU-TH) in Ishaka-Bushenyi in February 2024 in a wheelchair. His main complaint was lower limb weakness for about 2 months. The weakness was progressively worsening over days, making him walk at a slow pace with an abnormal gait and often times needing support. He reported no forgetfulness, loss of sensation, or abnormal sensation in any limb. He reported having no swelling, joint pain, muscle pain, or stiffness. Upon the review of other systems, he had no respiratory symptoms, no dyspepsia, normal bowel and micturition habits, no palpitations, no fever, and no weight loss. In his past medical history, he had a similar presentation in 2017 and was diagnosed to have vitamin B12 deficiency. The lumbar spine computed tomography (CT) scan performed during that time at Mayanja Memorial Hospital (in Mbarara, Western Uganda) showed mild lumbar spondylosis with no evidence of tumor or spinal cord compression. He was treated with parenteral methylcobalamin and oral folic acid and was advised to eat red meat. Had no known allergies to foods or drugs and no history of being dewormed in recent years. He denied taking any medication or herbal preparations and had no history of major abdominal surgery. He was from Bushenyi, Western Uganda, and was living with his wife and children. He denied a history of smoking and taking alcohol. His meals were mainly vegetables and occasionally meat and fish once or twice a week. There was no history of similar presentations or documented autoimmune conditions among siblings, parents, or children.

Physical examination revealed normal vital signs; the patient was afebrile and not wasted, with mild conjunctival pallor, no jaundice, no skin or nail findings noted, tongue changes, no palpable lymph nodes, and no lower limb edema. Systemic examination revealed the following: Glasgow coma scale was 15/15, there were negative signs of meningismus, his pupils were 3 mm each and reactive to light, and he had normal muscle power, tone, and sensation. However, he had a positive Romberg test and an unsteady gait. His muscles had normal bulkiness with no wasting or fasciculations, deep tendon reflexes and plantar reflexes showed normal findings focally, and no neurological deficits were noted. Abdominal examination showed normal findings; no tenderness or organomegaly was ascertained. On cardiorespiratory examination, the patient had bilateral equal air entry with normal vesicular breath sounds and normal S1 and S2 heart sounds with no added sound.

The complete blood count carried out in the preceding 2 weeks before the review showed macrocytosis with a mean corpuscular volume (MCV) of 114.4 fl (Table 1). The current blood count showed a mild decrease in all three cell lines, indicating macrocytic anemia (hemoglobin of 9.7 g/dl and MCV of 115 fl) (Table 2). With a positive history of vitamin B12 deficiency, serum vitamin B12 level was ordered and found to be low ( < 61 pmol/L) (Table 3). Given the recurrence, we ordered intrinsic factor antibodies (the blood sample was shipped to South Africa owing to a lack of a facility to perform the test in our area), which were positive (Table 3), thereby confirming pernicious anemia as a cause of recurrent B12 deficiency and the hematologic and neurologic manifestations. The patient was started on intramuscular methylcobalamin 1 mg daily for 1 week and oral folic acid 5 mg daily. He then received 1 mg of methylcobalamin weekly for a month and was scheduled for regular monthly reassessment and lifelong parenteral methylcobalamin therapy. During his follow-up, after the 4th to 6th month of being on the injection, he reported marked progressive improvement and was able to walk without support.

Table 1 Complete blood count carried out 2 weeks earlier

Table 2 Complete blood count carried out on the day of assessment

Table 3 Other laboratory workups performed

Discussion

Cobalamin is found largely in animal-based foods such as eggs, meat, and dairy products. The absorption of cobalamin at the terminal ileum is largely dependent on the intrinsic factor, a glycoprotein secreted by gastric parietal cells. Small amounts of cobalamin can be absorbed independent of the intrinsic factor (IF). Pernicious anemia (PA) is characterized by the presence of autoantibodies (IgG type) against the intrinsic factor and parietal cell. Intrinsic factor autoantibodies type I target the binding site of cobalamin, while type II are directed against IF’s binding to the mucosal epithelium of the terminal ileum, thereby interfering with normal cobalamin absorption. The peak postprandial serum cobalamin level is reached after 3–8 hours in these patients compared with 2 hours in normal individuals [1, 2].

PA has been reported among people of all ages worldwide, especially those over 60 years old [2, 3]. The prevalence of pernicious anemia in Africa has been reportedly low. The low prevalence may be explained by numerous diagnostic challenges in this setting. These factors may include a myriad of clinical presentations, a low index of suspicion, simultaneous occurrence with microcytic/normocytic anemias, the complexity of investigations, unavailability, and high costs of diagnostic investigations [1, 8]. In Uganda, vitamin B12 deficiency has been associated with nutritional deficiency, metformin use among those with diabetes mellitus, patients with the human immunodeficiency virus (HIV), pregnant women, and psychiatry patients [9, 10].

The presentation is often stealthy; the classic triad includes glossitis, jaundice, and myeloneuropathy [1, 3, 11, 12]. In our case study, the patient presented with neurological symptoms and macrocytic anemia.

A high index of suspicion, early diagnosis, and treating pernicious anemia are crucial in halting the progression of the disease. Late diagnosis may cause severe neurological disabilities [8]. If not treated early, fatal anemia and/or irreversible neurologic impairments may develop [1, 3]. A study in Italy reported an increased risk of gastric cancers and type I gastric neuroendocrine tumors in patients with PA [6]. Therefore, empiric therapy may be recommended in settings where complete laboratory workups are not feasible. For instance, in our case, we could not perform endoscopy and gastric mucosa studies (owing to unavailability of the test at the facility during the time of reviewing this patient).

Megaloblastic anemia has also been reported among patients with helminth infestations due to malabsorption [13, 14]. The stool analysis test of our patient was positive for Taenia sagnata and Strongyloides stercoralis, which might have contributed to the anemia.

The prevalence of PA is probably beyond the existing figures [6]. There was possibly a low index of suspicion for PA in this patient during the initial visit 7 years prior and the cobalamin deficiency was attributed to dietary intake. Routine screening of serum levels is only recommended for patients with risk factors, particularly, chronic gastrointestinal conditions, autoimmune diseases, and older age [15]. This case study serves as a remainder to healthcare workers on the importance of extended screening for high-risk patients, particularly those with anemia and/or neurologic symptoms. Homocysteine and methylmalonic acid are also among the important diagnostic elements for cobalamin deficiency as they can determine the clinical syndrome [8]. However, in this case, they were not carried out owing to the limited availability of the test in the local setting and the high costs of outsourcing.

The British Society of Haematology recommends much more aggressive parenteral therapy for patients with neurological manifestations than those without [15, 16]. Although it is called pernicious anemia, parenteral cobalamin therapy leads to the reversibility of bone marrow and most of the associated symptoms [1]. There are limited reports on this subject matter in most developing countries, particularly in Africa. Our patient reported improvement in walking after receiving several injections of methylcobalamin over the course of 6 months.

Conclusion

This case reveals a gap in diagnosing pernicious anemia in resource-limited settings and developing countries, particularly in rural regions. The epidemiological characteristics of pernicious anemia in such regions have been documented to be low, probably owing to incapacitated laboratory milestones. The scarcity of existing literature causes the problem to be overlooked. A high index of suspicion, early screening, and diagnosis are key to early treatment and hence, good patient outcomes. More studies should be performed to update the figures on the magnitude of pernicious anemia in developing countries. In a resource-limited setting, where most of the diagnostic workups may not be available, we suggest starting empiric methylcobalamin in patients suspected of having PA until the diagnosis is ruled out.