Giardiasis mimicking celiac disease in a patient of common variable immunodeficiency.

An adolescent boy presented to pediatrics outpatient department with complaints of recurrent diarrhea, nausea, vomiting, and pedal edema since 3-4 months, with no relief even after taking treatment. His investigation revealed decreased serum IgA, IgG, and IgM levels with hypoproteinemia. Duodenal biopsy showed features of celiac disease (CD), but tissue transglutaminase IgA was negative. In stool examination, plenty of Giardia lamblia cysts and eggs of Hymenolepis nana were present. He improved on treatment and remained asymptomatic for 4 months. However, he again developed symptoms and succumbed to his illness. In patients of common variable immunodeficiency (CVID), who present with features of CD, coinfection, especially with G. lamblia and other parasites must always be kept in mind. The aim is to report a case of recurrent giardiasis with CVID mimicking CD from Western Rajasthan, India.

INTRODUCTION

Incidence of intestinal infections with parasites is higher in developing countries due to the poor sanitary conditions, poor personal hygiene, and use of contaminated drinking water.[1] Such infections are more common in the immunocompromised persons.[2] Common variable immunodeficiency (CVID) is a heterogeneous group of disorders having both B-cell and T-cell dysfunctions. The usual presenting features of CVID are recurrent infections of different organs of the body. The gastrointestinal tract (GIT) infections include features of malabsorption or chronic diarrhea, protein-losing enteropathy, and recurrent infection of the small bowel with bacteria such as Campylobacter or Yersinia species or with parasites such as Giardia lamblia.[3] The loss of intestinal villi is frequently seen in the biopsy findings of patients with CVID.[3] All these features mimic celiac disease (CD), which is a chronic inflammatory small bowel disorder arising due to irritant gluten in persons due to genetic and possibly other environmental cofactors.[4] Here is a case of recurrent Giardiasis who presented with clinical as well as histolopathological features of CD, and on subsequent investigations, he was found to be suffering from CVID.

CASE REPORT

A 16-year-old male presented to pediatric outpatient department with a history of loose stool (5–10 episodes daily, not associated with mucous or blood), pedal edema (which increased in the evening), nausea and vomiting (10–15 episodes per day), and puffiness of eyes from 3 to 4 months. He also complained of burning micturition and decreased urine output for 15–20 days and suprapubic pain from 2 days. He had consulted several physicians in local area but with no relief. His previous reports showed the presence of giardia cysts in stool microscopy, negative stool occult blood, and negative Sudan-III test. The liver function test was normal except raised alkaline phosphatase (606 U/L). Total protein was decreased (3.9 g/dl) and albumin (2.2 g/dl) and globulin (1.7 g/dl) were also low. Complete blood counts, blood sugar, kidney function test, serum uric acid, and 24 h urine protein excretion were within normal limit. Anti-HIV, HbsAg, and anti-HCV antibodies were negative.

On general examination, the physical condition of the patient was normal and vitals were stable. Pedal edema was pitting in nature. There were no other significant systemic findings. A presumptive diagnosis of chronic diarrhea under evaluation with urinary tract infection was made, and the patient was admitted to the pediatric ward. On hematological examinations, all parameters were within normal limits except neutrophilia (85%). Total protein (3.26 g/dl), albumin (1.48 g/dl), and globulin (1.78 g/dl) levels were decreased. Serum sodium and potassium levels were within normal limit. Urine routine microscopy showed trace proteinuria and culture showed insignificant growth of microorganism. Renal function tests and liver function tests were normal. Total, direct, and indirect bilirubin levels were within normal limits. Ultrasonography of abdomen and pelvis showed mild hepatomegaly and mild ascites. Tissue transglutaminase (tTG) IgA was 2.72 IU/ml (<10 IU/ml is Negative). Colonoscopy till 5 cm of terminal ileum showed normal mucosa, without any growth or ulcer. Gastrointestinal endoscopy was done up to D2 level. Milky fluid was seen coming from duodenum, with edematous mucosa in D1 region and multiple whitish spots in D2 region. Biopsy was taken from D2 region and sent for histopathological examination which showed blunting of villi, heavy epithelial infiltration of lymphocytes involving the surface epithelium, and deeper crypts with lamina propria showing edema and inflammation predominantly with plasma cells mixed with lymphocytes and eosinophils [Figure 1]. Muscularis mucosa was normal. Furthermore, there was Paneth cell hyperplasia. These findings were consistent with those of CD. Computed tomography abdomen with enterography was also done which showed features of pancolitis, possibly infective colitis. When stool examination was done, it showed the presence of plenty of cysts of G. lamblia and eggs of Hymenolepis nana [Figure 2]. Furthermore, serum IgA level was 0.483 (normal range 0.57–5.34 g/L), IgG level was 2.70 g/L (normal range 6.5–16.2 g/L), and IgM level was 0.29 g/L (normal range 0.30–2.65 g/L). All serum immunoglobulins were low, arousing a suspicion of CVID. Patient was administered nitazoxanide (500 mg 1 tablet BD for 3 days), praziquantel 600 mg stat, metronidazole 400 mg tid for 7 days, cefixime (200 mg BD), tetracycline 250 mg BD, folic acid 5 mg, and injection trineurosol-H (vitamin B1, B6, and B12) along with plenty of electrolytes and fluids and gluten-free high protein diet. There was symptomatic relief and patient was discharged after 8 days.

Figure 1

Duodenal biopsy showing dense submucosal infiltration of lymphocytes, plasma cells, and eosinophils (H and E, ×40)

Figure 2

Direct and iodine wet mount of stool (×40), presence of cysts of Giardia lamblia, and eggs of Hymenolepis nana

His condition remained stable for about 4 months, after which he was readmitted with complaints of loose stool and edema of lower limbs. This time, stool routine and microscopic examination was normal. Repeat serum tTG IgA was <3 IU/mL (negative), serum IgG was 4.7 g/L (low), and serum IgM was 0.66 g/L (normal). Serum anti-Saccharomyces cerevisiae antibody IgA and IgG was also done to rule out the possibility of inflammatory bowel disease, both of which were <3 AU/mL (<12 AU/mL is negative). Increased levels of serum glutamate pyruvate transaminase (59 IU/L), serum glutamic oxaloacetic transaminase (56 IU/L), and serum lactate dehydrogenase level (624 U/L) were found. At the same time, the level of total serum protein (2.67 g/dl) and serum albumin (1.6 g/dl) were found to be decreased. Colonoscopy showed normal study. He was treated with ciprofloxacin, metronidazole, and injections of albumin. His conditions became stable, and he was discharged after 7 days with an advice to take multivitamin and iron tablets along with gluten-free, protein-rich diet.

On further follow-up, he remained well for 2 months, after which his condition started to deteriorate again, and he was admitted to a local hospital in critical condition where he died.

DISCUSSION

Almost half of the patients with CVID have GIT problems. The increased tendency of G. lamblia infection has been noted in CVID patients leading to damage of enterocytes, subtotal villous atrophy, and development of a nodular mucosal pattern.[3] This case presented with G. lamblia and H. nana infestations, along with low immunoglobulin levels and the duodenal biopsy characteristically resembling to CD. The patient's serum tTG IgA was negative even when he was on gluten-containing diet. These findings are not in favor of CD. IgG-based tTG and deamidated gliadin peptides test, which should be done in patients with low IgA level, could not be done in this case. However, repeated decrease in the immunoglobulin levels and recurrent gastrointestinal infections resulting into diarrhea suggests that the patient had CVID. As discussed, giardiasis and CVID both have the potential to cause villous atrophy. There are many case reports and studies relating to CVID and Giardiasis.[3567] For more than 20 years, IVIG has been used in the treatment of a wide range of primary and secondary immunodeficiency including CVID.[8] In this case, no immunoglobulin could be prescribed, which definitely might have changed the scenario. Furthermore, there was a coinfection of G. lamblia and H. nana, which might have possibly added to the severity of the GIT symptoms such as chronic diarrhea. The cause of his death may be multifactorial including recurrent gastrointestinal infections, severe malabsorption and nutritional deficiency, severe weakness or electrolyte imbalance, and others.

CONCLUSION

Parasitological coinfection must always be kept in mind when investigating a patient of CVID, presenting with features of CD, especially G. lamblia and others. The severity of illness in such cases can lead to increased morbidity and mortality.

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Conflicts of interest

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