REVIEWS OF INFECTIOUS DISEASES • VOL. 12, NO. 2 • MARCH-APRIL 1990 © 1990 by The University of Chicago. All rights reserved. 0162-0886/90/1202-0014$02.00
Acute Appendicitis Complicating Infectious Mononucleosis: Case Report and Review Antonio I.opez-Navidad, Pere Domingo, J osep Cadafalch, J ordi Farrerons, Luis Allende, and Ramon Bordes
From the Departments of Internal Medicine, Surgery, and Pathology, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain
The clinical manifestations of infectious mononucleosis (1M) represent the final result of the extensive lymphoproliferative T cell response directed against Epstein-Barr virus (EBV)-infected B lymphocytes [1]. The production of great numbers of activated T lymphocytes and the lymphocytic infiltration of organs and tissues cause generalized lymph node hyperplasia, hepatosplenomegaly, tonsillar and adenoidal changes, as well as the characteristic blood picture with the finding of large numbers of atypical lymphocytes [1, 2]. Virtually all organs and tissues may be involved in 1M, a fact that may explain the protean presentation of the disease [3]. Abdominal pain is an uncommon clinical feature of 1M and is usually attributed to involvement of the spleen, intraabdominallymph nodes, gut-associated lymphoid tissue (GALT), and/or hepatitis [4].
Involvement of GALT might be expected in 1M because of the marked tropism of EBV for lymphocytes; however, only isolated cases of such involvement have been reported in the literature [4-6]. Despite the fact that the appendix is primarily a lymphatic organ, acute appendicitis has rarely been reported in association with 1M [7-10]. Such cases have been cited in isolated reports and general reviews of the disease, but neither these reports nor a recent textbook devoted to 1M [11] recognizes acute appendicitis as a complication of 1M. To date, there has been no comprehensive review of acute appendicitis complicating 1M. We report a case of acute appendicitis that developed during the acute phase of 1M. Because of the diagnostic challenge presented by this case and the unique histopathologic findings in the appendix, we reviewed other cases published in the literature.
Received for publication 29 August 1988and in revised form 20 July 1989. The authors are indebted to Dr. Gary R. Pearson (Department of Microbiology, Georgetown University Medical Center, Washington, D.C.) for performing the anticomplementary immunofluorescent staining of the appendix for EBNA and for his critical reviewof the manuscript, to Dr. Lothar Sand for his translation of German articles, and to Sr. Juan Carlos Nieto for his technical assistance. Please address requests for reprints to Dr. Pere Domingo, Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Avgda Sant Antoni M" Claret, 167, 08025 Barcelona, Spain.
Case Presentation A 17-year-old boy was admitted to the hospital with a 2-day history of colicky abdominal pain in the right lower quadrant, vomiting, and diarrhea. Three weeks earlier, he had complained of malaise, fever, and sore throat; septic tonsillitis was diagnosed and sequentially treated with amoxicillin, erythromycin, and penicillin, without improvement. On examination, the patient had a fever of 39°C; his throat was in-
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Downloaded from http://cid.oxfordjournals.org/ at New York University on July 26, 2015
Acute appendicitis is an uncommon complication of infectious mononucleosis (1M) and can readily be misdiagnosed because of the acute abdominal pain with which patients with 1M occasionally present. A case report is presented of a patient with 1M who developed acute appendicitis during the acute phase of the illness. The appendicitis progressed to the formation of an abscess, which was evacuated at surgery. Histologic examination of the appendix showed absence of lymphoid follicles in the mucosal layer and intense lymphoid infiltration of the mucosa and submucosa by a mixed diffuse proliferation of lymphoid cells with groups of immunoblasts scattered among them. The lymphoid infiltrate was mainly composed of T lymphocytes; the anticomplementary immunofluorescent staining of the appendix for EBNA (Epstein-Barr nuclear antigen) was negative.Three cases of appendicitis complicating 1M published in the literature are reviewed. All had clinical and histopathologic features similar to those of our patient and were cured after surgery. Our case report together with the literature review confirms that appendicitis in the acute phase of 1M has distinct clinical and histopathologic features and thus has to be considered a true complication of 1M rather than merely a simultaneous disease.
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Figure 1. Photomicrograph of the appendix showing an intense lymphocytic infiltration of mucosa and submucosa (hematoxylin-eosin stain; original magnification, X 1(0) .
phoid follicles had disappeared from the mucosal layer. The lymphoid infiltrate was mainly composed of mature lymphocytes with groups of immunoblasts scattered among them; these cells typically had a big nucleus, frequent mitoses, and a basophilic cytoplasm (figure 2). The mucosal glands also appeared to be infiltrated by lymphocytes with frequent mitoses and to have partially lost their mucus-secreting ability. Staining with monoclonal antibodies demonstrated that the appendiceal infiltrate consisted predominately of T lymphocytes. Furthermore, the appendix specimen was stained byanticomplementary immunofluorescence for EBNA (Epstein-Barr nuclear antigen) with negative results (Dr. Gary R. Pearson, Department of Microbiology, Georgetown University Medical Center). After surgery, antibiotic therapy was continued for 10 days. The postoperative course was uneventful, and the patient wasdischarged in good health 20 days after admission. Literature Review The MEDLINE database was searched through May 1988 for cases of acute appendicitis complicating 1M. Cases were included only if the diagnosis of 1M fulfilled the criteria stated by Penman [12] and if the patients developed acute appendicitis, documented at laparotomy, during the acute phase of 1M. The three cases found are summarized in table 1. An additional case reported by Fisher et al. [9] is not included in the table because of the lack of data.
Downloaded from http://cid.oxfordjournals.org/ at New York University on July 26, 2015
flamed, with large erythematous tonsils covered by a purulent exudate. Cervical, axillary, and inguinal lymph nodes were enlarged and tender, with fading macular skin rash over the trunk. Abdominal examination showed guarding and tenderness of the lower abdomen with rebound tenderness in the right lower quadrant. The spleen tip was palpable. On rectal examination the right iliac fossa was not tender. Thoracic and abdominal radiographs were normal. The white blood cell (WBC) count on admission was 15,700/mm J , with 570/0 neutrophils, 2% band forms, 36% lymphocytes (of which 21 % were atypical lymphocytes), and 5010 monocytes. The hemoglobin concentration was 13.7 g/dL, the albumin 29 giL (normal, 36-51), and y-globulins 17.3g/dL (normal 8.5 to 14). The AST (aspartate aminotransferase) value was 43 U/L (normal,
Acute Appendicitis Complicating Infectious Mononucleosis: Case Report and Review Antonio I.opez-Navidad, Pere Domingo, J osep Cadafalch, J ordi Farrerons, Luis Allende, and Ramon Bordes
From the Departments of Internal Medicine, Surgery, and Pathology, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain
The clinical manifestations of infectious mononucleosis (1M) represent the final result of the extensive lymphoproliferative T cell response directed against Epstein-Barr virus (EBV)-infected B lymphocytes [1]. The production of great numbers of activated T lymphocytes and the lymphocytic infiltration of organs and tissues cause generalized lymph node hyperplasia, hepatosplenomegaly, tonsillar and adenoidal changes, as well as the characteristic blood picture with the finding of large numbers of atypical lymphocytes [1, 2]. Virtually all organs and tissues may be involved in 1M, a fact that may explain the protean presentation of the disease [3]. Abdominal pain is an uncommon clinical feature of 1M and is usually attributed to involvement of the spleen, intraabdominallymph nodes, gut-associated lymphoid tissue (GALT), and/or hepatitis [4].
Involvement of GALT might be expected in 1M because of the marked tropism of EBV for lymphocytes; however, only isolated cases of such involvement have been reported in the literature [4-6]. Despite the fact that the appendix is primarily a lymphatic organ, acute appendicitis has rarely been reported in association with 1M [7-10]. Such cases have been cited in isolated reports and general reviews of the disease, but neither these reports nor a recent textbook devoted to 1M [11] recognizes acute appendicitis as a complication of 1M. To date, there has been no comprehensive review of acute appendicitis complicating 1M. We report a case of acute appendicitis that developed during the acute phase of 1M. Because of the diagnostic challenge presented by this case and the unique histopathologic findings in the appendix, we reviewed other cases published in the literature.
Received for publication 29 August 1988and in revised form 20 July 1989. The authors are indebted to Dr. Gary R. Pearson (Department of Microbiology, Georgetown University Medical Center, Washington, D.C.) for performing the anticomplementary immunofluorescent staining of the appendix for EBNA and for his critical reviewof the manuscript, to Dr. Lothar Sand for his translation of German articles, and to Sr. Juan Carlos Nieto for his technical assistance. Please address requests for reprints to Dr. Pere Domingo, Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Avgda Sant Antoni M" Claret, 167, 08025 Barcelona, Spain.
Case Presentation A 17-year-old boy was admitted to the hospital with a 2-day history of colicky abdominal pain in the right lower quadrant, vomiting, and diarrhea. Three weeks earlier, he had complained of malaise, fever, and sore throat; septic tonsillitis was diagnosed and sequentially treated with amoxicillin, erythromycin, and penicillin, without improvement. On examination, the patient had a fever of 39°C; his throat was in-
297
Downloaded from http://cid.oxfordjournals.org/ at New York University on July 26, 2015
Acute appendicitis is an uncommon complication of infectious mononucleosis (1M) and can readily be misdiagnosed because of the acute abdominal pain with which patients with 1M occasionally present. A case report is presented of a patient with 1M who developed acute appendicitis during the acute phase of the illness. The appendicitis progressed to the formation of an abscess, which was evacuated at surgery. Histologic examination of the appendix showed absence of lymphoid follicles in the mucosal layer and intense lymphoid infiltration of the mucosa and submucosa by a mixed diffuse proliferation of lymphoid cells with groups of immunoblasts scattered among them. The lymphoid infiltrate was mainly composed of T lymphocytes; the anticomplementary immunofluorescent staining of the appendix for EBNA (Epstein-Barr nuclear antigen) was negative.Three cases of appendicitis complicating 1M published in the literature are reviewed. All had clinical and histopathologic features similar to those of our patient and were cured after surgery. Our case report together with the literature review confirms that appendicitis in the acute phase of 1M has distinct clinical and histopathologic features and thus has to be considered a true complication of 1M rather than merely a simultaneous disease.
Lopez-Navidad et al.
298
Figure 1. Photomicrograph of the appendix showing an intense lymphocytic infiltration of mucosa and submucosa (hematoxylin-eosin stain; original magnification, X 1(0) .
phoid follicles had disappeared from the mucosal layer. The lymphoid infiltrate was mainly composed of mature lymphocytes with groups of immunoblasts scattered among them; these cells typically had a big nucleus, frequent mitoses, and a basophilic cytoplasm (figure 2). The mucosal glands also appeared to be infiltrated by lymphocytes with frequent mitoses and to have partially lost their mucus-secreting ability. Staining with monoclonal antibodies demonstrated that the appendiceal infiltrate consisted predominately of T lymphocytes. Furthermore, the appendix specimen was stained byanticomplementary immunofluorescence for EBNA (Epstein-Barr nuclear antigen) with negative results (Dr. Gary R. Pearson, Department of Microbiology, Georgetown University Medical Center). After surgery, antibiotic therapy was continued for 10 days. The postoperative course was uneventful, and the patient wasdischarged in good health 20 days after admission. Literature Review The MEDLINE database was searched through May 1988 for cases of acute appendicitis complicating 1M. Cases were included only if the diagnosis of 1M fulfilled the criteria stated by Penman [12] and if the patients developed acute appendicitis, documented at laparotomy, during the acute phase of 1M. The three cases found are summarized in table 1. An additional case reported by Fisher et al. [9] is not included in the table because of the lack of data.
Downloaded from http://cid.oxfordjournals.org/ at New York University on July 26, 2015
flamed, with large erythematous tonsils covered by a purulent exudate. Cervical, axillary, and inguinal lymph nodes were enlarged and tender, with fading macular skin rash over the trunk. Abdominal examination showed guarding and tenderness of the lower abdomen with rebound tenderness in the right lower quadrant. The spleen tip was palpable. On rectal examination the right iliac fossa was not tender. Thoracic and abdominal radiographs were normal. The white blood cell (WBC) count on admission was 15,700/mm J , with 570/0 neutrophils, 2% band forms, 36% lymphocytes (of which 21 % were atypical lymphocytes), and 5010 monocytes. The hemoglobin concentration was 13.7 g/dL, the albumin 29 giL (normal, 36-51), and y-globulins 17.3g/dL (normal 8.5 to 14). The AST (aspartate aminotransferase) value was 43 U/L (normal,
