diffuse nodular lymphoid hyperplasia ( dnlh ) of the gastrointestinal tract is a rare disease characterized by numerous small polypoid nodules in the small intestine , large intestine , or both ( 1 ) . the pathogenesis of dnlh is uncertain , but it may be related to the immune status . this condition may arise as compensation for insufficient intestinal lymphoid tissue in immunodeficiency , or it may be related to repeated immune stimulation of intestinal lymphoid tissue , such as infection , in immunocompetent patients ( 2,3 ) . it is associated with immunodeficiency , including common variable immunodeficiency ( cvid ) , selective iga deficiency , and human immunodeficiency virus ( hiv ) infection , and infections , such as giardia lamblia and helicobacter pylori ( 3 - 5 ) . although several cases of dnlh associated with cvid and giardiasis have been reported ( 6 - 8 ) , so far very few studies have reported a regression of the lymphoid nodules after the eradication of infection ( 6 ) . we herein describe a case of dnlh of the intestine associated with cvid and giardiasis which markedly improved after successfully treating giardiasis . a 41-year - old woman visited an out - patient clinic for an evaluation of dnlh that had been incidentally detected two years previously . she had been admitted to our hospital for the treatment of acute pyelonephritis one year prior . although she had received vaccines against hepatitis b , she did not produce antibody against hepatitis b. her family history was unremarkable . on physical examination , she had no signs of fever , weight loss , night sweats , or autoimmune phenomena . laboratory tests showed a hemoglobin level of 12.3 g / dl , a white blood cell count of 9,100/l , a platelet count of 266,000/l , and normal kidney and liver function tests . antinuclear antibody was skeleton level 2 ( 1 : 80 ) , and c3 and c4 were within the normal range . however , here serum immunoglobulin levels were markedly decreased , with immunoglobulin g ( igg ) of 175.0 mg / dl ( normal range : 751 - 1,560 mg / dl ) , iga of less than 7.3 mg / dl ( 82 - 453 ) , and igm of 36.6 mg / dl ( 46 - 304 ) . esophagogastroduodenoscopy ( egd ) showed numerous mucosal nodular lesions in the second portion of the duodenum , and campylobacter - like organism ( clo ) tests were negative . there were numerous small nodular lesions in the entire small bowel from the duodenum to the terminal ileum in a small bowel series ( fig . esophagogastroduodenoscopy ( egd ) and colonoscopy demonstrated numerous diffuse mucosal nodular lesions in the second portion of the duodenum ( a ) and colon ( b ) . on follow - up egd and colonoscopy , the size and number and of mucosal nodular lesions in the duodenum ( c ) and colon ( d ) had remarkably decreased compared with the lesions observed 2 years previously . a small bowel series showed numerous small nodular lesions throughout the entire small bowel loop from the duodenum to the terminal ileum . an endoscopic biopsy showed a relatively well preserved mucosal architecture and many hyperplastic lymphoid follicles with expansile reactive germinal centers and sharply delineated bands of mantle zones . ( a ) a low power view of the duodenal mucosal tissue showed relatively well - preserved villous epithelial architecture and well - formed lymphoid follicles in the lamina propria [ hematoxylin and eosin ( h&e ) staining , 40 ] . ( b ) a high power view showed expansile hyperplastic germinal centers demonstrating well - preserved polarity from the dark to light zone , characteristics of reactive germinal centers , and sharply delineated by a thin layer of mantle zone ( h&e staining , 200 ) . immunohistochemical staining showed the characteristic features of reactive lymphoid hyperplasia with cd20 ( c ) , cd3 ( d ) , and bcl-2 ( e ) . ( f ) no lymphoepithelial lesions were noted on immunohistochemical staining for cytokeratin ( 100 ) . 
  among the first line therapies for giardiasis , only metronidazole was available at our clinic . therefore , she received metronidazole [ 250 mg per os ( po ) ] three times a day for 5 days , but there was no response . as an alternative treatment , albendazole ( 400 mg po once a day for 5 days ) was prescribed ( 9 ) . tinidazole was then selected for the third treatment with a longer duration ( 2 g po once a day for 5 days ) , however , the giardiasis could not be eradicated . finally , we decided to treat suspected nitroimidazole - resistant giardia with metronidazole ( 500 mg po two times a day ) in combination with albendazole ( 400 mg po once a day ) . after 2 weeks of treatment , the results of a stool examination showed a negative result for giardia ( 10 ) . diffuse nodular lesions still existed from the duodenum to the colon , but they had remarkably decreased in size compared with the lesions that had been observed two years previously ( fig . her serum immunoglobulin levels were still very low after eradication with igg of 160.0 mg / dl , iga of less than 7.3 mg / dl , and igm of 14.9 mg / dl . although she refused to undergo immunoglobulin treatment , she was able to return to her normal daily life and physical activities without any complications until now . cvid , a heterogeneous disease associated with a failure to produce immune globulins and protective antibodies , is diagnosed by low levels of serum igg , iga , and/or igm , impaired antibody production to vaccination , and the exclusion of other causes of failure of immunoglobulin production ( 11,12 ) . in our case , the diagnosis of cvid was delayed by 2 years after the incidental detection of dnlh because the patient had no specific symptoms , except for intermittent diarrhea . since dnlh is associated with immunodeficiency , we performed careful history taking and several tests to determine her immunodeficient status . she could not produce hepatitis b surface antibody after vaccination , but she had no other immunodeficiency . it can cause various clinical features from asymptomatic infection to chronic diarrhea and severe malabsorption . giardia infection may be more intense and persistent in an immunodeficient host , such as in this case ( 13 ) . although our case showed treatment - resistant giardiasis , we were able to successfully eradicate g. lamblia after changing the therapeutic agents four times . the diffuse nodular lesions on the egd just before successfully treating the giardiasis were very similar compared with the lesions on an initial egd examination performed two years previously . the patient did not receive any other treatment except for eradication of giardiasis and the diffuse nodular lesions remarkably decreased after successfully treating giardiasis . therefore , we assumed that the giardia infection played an essential role in the development of dnlh in this case . the overall survival of cvid has improved due to replacement of immune globulin and improved microbial therapies . however , immunoglobulin can not control other important complications , including chronic lung disease , autoimmunity , gastrointestinal disease , and neoplasms , such as non - hodgkin 's lymphoma and gastric cancer ( 11,12 ) . while there is no standard follow - up schedule , it is important to keep monitoring the patient 's medical history , physical examination , and several tests ( 12 ) . although our patient refused immunoglobulin treatment , she was able to lead a normal , active life without severe infection after diagnosis of cvid . she has regularly visited on our clinic and had regular work - ups , including blood tests , chest x - ray , and cancer surveillance . in summary , we documented a case of dnlh of the intestine due to cvid and giardiasis . because dnlh is associated with immunodeficiency and parasitic infections , it is essential for patients with dnlh to be evaluated for these diseases . in addition , cvid patients should undergo long - term surveillance for various complications , including the development of malignancy .
diffuse nodular lymphoid hyperplasia of the gastrointestinal tract is a rare disease characterized by numerous small polypoid nodules in the small intestine , large intestine , or both . 
 it is associated with immunodeficiency and infection , such as giardia lamblia and helicobacter pylori . 
 although diffuse nodular lymphoid hyperplasia associated with common variable immunodeficiency ( cvid ) and giardiasis is already known , a few studies have reported a regression of the lymphoid nodules after the eradication of infection . 
 we herein describe a case of diffuse nodular lymphoid hyperplasia of the intestine associated with cvid and refractory giardiasis that markedly improved after successfully treating giardiasis .