susceptibility studies, further supporting the hypothesis of hematogenous spread of infection originating from the Bartholin abscess. Diagnosis of sternoclavicular septic arthritis, made from joint fluid culture, is often delayed or missed as a result of the insidious onset of subacute symptoms.6 Radiologic abnormalities are not always obvious; 85% of plain radiographs appear normal even in advanced disease, and only 25% of computed tomography scans demonstrate joint space widening or effusion.6 Certainly, the vague symptoms and normal radiologic studies contributed to our delay in diagnosis. Our patient clinically improved after joint aspiration, which served both as a diagnostic and therapeutic procedure in removing the remaining source of infection. Nonetheless, even in the setting of prompt treatment, patients with septic arthritis have a substantial risk of severe morbidity with long-term disability, including a 10% risk of mortality.5 At the time of this writing, our patient has completed 4 weeks of oral antibiotic therapy with slow clinical recovery. She reports no deficits in her range of motion and minimal symptoms of pain. Although rare, the complications of Bartholin gland abscess in pregnancy can be severe, resulting
in overwhelming infection and widespread hematogenous seeding. The rarity of clinical studies regarding abscess drainage in pregnancy makes recommendations regarding antibiotic coverage challenging, and empiric treatment in these patients has previously been suggested. The possible consequences of simple abscess drainage should not be underestimated in these patients, and close follow-up should be established to ensure clinical improvement.
Hemophagocytic Lymphohistiocytosis Associated With a Parvovirus B19 Infection During Pregnancy
CASE: We present a case of parvovirus B19 infection related to hemophagocytic lymphohistiocytosis during pregnancy. The patient experienced fever and pancytopenia. A bone marrow biopsy demonstrated hemophagocytosis and a giant proerythroblasts, which is characteristic of a parvovirus B19 infection. Viral serology for parvovirus B19 was positive. Prompt treatment was started because of the high level of certainty of viral-associated hemophagocytic lymphohistiocytosis, and the patient was successfully treated with prednisolone administration. She delivered a healthy newborn without any complications.
Michinori Mayama, MD, Masato Yoshihara, MD, Tetsuya Kokabu, MD, and Hidenori Oguchi, MD, PhD BACKGROUND: Hemophagocytic lymphohistiocytosis is potentially fatal. Prompt diagnosis and initiation of treatment are critical for ensuring the best possible prognosis.
REFERENCES 1. Kessous R, Barak A, Boaz S, Shteiner N, Moran-Gilad J, Weintraub A. Clinical and microbiological characteristics of Bartholin gland abscesses. Obstet Gynecol 2013;122:794–9. 2. Lopez-Zeno J, Ross E, O’Grady J. Septic shock complicating drainage of a Bartholin gland abscess. Obstet Gynecol 1990;76:915–6. 3. Luppi P. How immune mechanisms are affected by pregnancy. Vaccine 2003;21:3352–7. 4. Barton JR, Sibai BM. Severe sepsis and septic shock in pregnancy. Obstet Gynecol 2012;120:689–706. 5. Womack J. Septic arthritis of the sternoclavicular joint. J Am Board Fam Med 2012;25:908–12. 6. Ross JJ, Shamsuddin H. Sternoclavicular septic arthritis: review of 180 cases. Medicine 2004;83:139–48.
CONCLUSION: Hemophagocytic lymphohistiocytosis should be considered when encountering unexplained cytopenia and fever. Prednisolone was an effective treatment. (Obstet Gynecol 2014;124:438–41) DOI: 10.1097/AOG.0000000000000385
From the Department of Obstetrics, Perinatal Medical Center, Toyota Memorial Hospital, Toyota, Aichi, Japan. The authors thank Shinichi Mizuno for his knowledge of hemophagocytic lymphohistiocytosis, and Yasuyuki Kishigami for checking our manuscript and providing constructive comments from preparation to revision. Corresponding author: Michinori Mayama, 20-2, Misato-cho, Toyota, Aichi, Japan; e-mail: [email protected]. © 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
438
Mayama et al
Hemophagocytic Lymphohistiocytosis
H
emophagocytic lymphohistiocytosis is a rare disorder characterized by systemic benign proliferation of histiocytes in a hyperinflammatory state and phagocytosis of hematopoietic elements. Hemophagocytic lymphohistiocytosis can be classified according to the underlying etiology into either familial or acquired forms. Familial hemophagocytic lymphohistiocytosis often occurs during infancy and early childhood, and
OBSTETRICS & GYNECOLOGY
it is associated with an autosomal recessive inheritance pattern in most cases. Acquired hemophagocytic lymphohistiocytosis generally occurs in older children and adults who have no known genetic causes or family history, and it is associated with various infectious, malignant, metabolic, and rheumatologic conditions.1 The major signs and symptoms of hemophagocytic lymphohistiocytosis are fever, hepatosplenomegaly, and cytopenia in at least two cell lines. Less frequently observed symptoms are rash, lymphadenopathy, icterus, and neurologic symptoms. Hemophagocytic lymphohistiocytosis is potentially fatal, and early initiation of treatment is necessary for the best possible prognosis. However, establishing a diagnosis quickly is often challenging because of the nonspecific symptoms of hemophagocytic lymphohistiocytosis. Hemophagocytic lymphohistiocytosis is a rare disorder, especially in cases involving pregnancies. A nationwide survey in Japan reported that among 567 patients with hemophagocytic lympohistiocytosis, 301 cases (53.1%) were related to infection.2 In the infection-associated cases, Epstein–Barr virus is a predominant cause (163 cases, 54.2%), and only three cases (1.0%) were caused by parvovirus B19.2
CASE A 28-year-old woman, gravida 2 para 2, at 20 1/7 weeks of gestation with a 3-day history of fatigue, dizziness, and fever was admitted to the hospital. Pancytopenia was detected at the hospital, and the patient was then transferred to our hospital. Mild anemia had been detected in the patient during the first trimester and was managed with oral iron therapy. She had not been experiencing any other complications during this pregnancy. On admission, her vital signs were as follows: temperature 38.1˚C; blood pressure 101/50 mm Hg; and heart rate 111 beats per minute. No symptoms of significant swelling of superficial lymph nodes, hepatomegaly, or splenomegaly were observed during the physical examination. Initial laboratory results showed pancytopenia with a hemoglobin level of 4.2 g/dL, a white blood cell count of 600/microliter (neutrophils 44%, lymphocytes 39%, monocytes 11%), and a platelet count of 83,000/
Box 1. Diagnostic Criteria for Hemophagocytic Lymphohistiocytosis3 Molecular diagnosis of hemophagocytic lymphohistiocytosis or the presence of at least five of eight criteria: 1. Fever 2. Splenomegaly 3. Cytopenia (affecting at least two lineages in the peripheral blood) Hemoglobin less than 9.0 g/dL, platelets less than 100,000/microliter, neutrophils less than 1,000/ microliter 4. Hypertriglyceridemia or hypofibrinogenia Fasting triglycerides 3.0 mmol/L or more (265 mg/dL or more), fibrinogen 1.5 g/L or less 5. Hemophagocytosis in bone marrow, spleen, or lymph nodes 6. Low or absent natural killer cell activity 7. Ferritin 500 ng/mL or more 8. Soluble CD25 (soluble interleukin-2 receptor) 2,400 units/mL or more Modified from Henter JI, Horne A, Arico´ M, Egeler RM, Filipovich AH, Imashuku S. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124–31. Copyright 2006 Wiley-Liss, Inc.
microliter. An elevation of lactate dehydrogenase 277 international units/L (119–229 international units/L) and serum ferritin 1,269.2 ng/mL (5.0–177.6 ng/mL) were observed, but her liver and kidney function test results, plasma electrolytes, and coagulation status were all within normal limits. An ultrasonography revealed no evidence of fetal distress or fetal hydrops. A bone marrow biopsy detected increased numbers of histiocytes engulfing erythroid precursors, as well as neutrophils and platelets. Giant proerythroblasts, which are characteristic of parvovirus B19 infections, were also detected (Fig. 1A and 1B). Hemophagocytic syndrome associated with a parvovirus B19 infection was suspected. We began the administration of prednisolone in 40-mg daily dosages. The patient received a transfusion with 4 units of red blood cells to treat severe anemia. Her red blood cell, white blood cell, and platelet counts began to recover, so we started tapering prednisolone dosages
Fig. 1. Bone marrow biopsy revealed histiocytes with hemophagocytosis (A) and giant proerythroblast (B). Mayama. Hemophagocytic Lymphohistiocytosis. Obstet Gynecol 2014.
A
VOL. 124, NO. 2, PART 2, AUGUST 2014
B
Mayama et al
Hemophagocytic Lymphohistiocytosis
439
40mg
30mg 20mg
15mg
20mg Prednisolone
25
20
WBC (x 103 μL)
15
Hemoglobin (g/dL) Platelets (x 104 μL)
10
Fig. 2. Clinical course. Medication dosages and changes in white blood cells (WBC), hemoglobin, and platelets are shown.
5
0
0
1
5
20
40
60
84
100
124
Days post admission
gradually on hospital day 5 (Fig. 2). Additional serological test results showed parvovirus B19 antibody titers of immunoglobulin M and immunoglobulin G of 9.10 and 7.25; 2 weeks later, they were 9.88 and 8.48 (normal range less than 0.79 and less than 0.79). Viral serology tests for Epstein–Barr virus and cytomegalovirus were negative. These results confirmed the diagnosis of hemophagocytic lymphohistiocytosis associated with parvovirus B19 infection. During the remainder of her pregnancy, excellent disease management was maintained without fetal distress or fetal growth restriction. At 37 4/7 weeks of gestation, she delivered a 2,876-g male newborn by normal vaginal delivery with Apgar scores of 9 and 10 at 1 minute and 5 minutes, respectively.
COMMENT Early diagnosis of hemophagocytic lymphohistiocytosis and prompt initiation of treatment are essential because delaying therapy may lead to irreversible multiple organ failure. The diagnostic criteria of hemophagocytic lymphohistiocytosis are listed in Box 1. These criteria have been widely used; however, other diagnostic criteria, especially for acquired hemophagocytic lymphohistiocytosis in adults, are necessary because these criteria were mainly composed using the data of familial hemophagocytic lymphohistiocytosis in pediatric cases.4 Timely diagnosis is often challenging because of the nonspecific clinical presentations of hemophagocytic lymphohistiocytosis. Bone marrow biopsy is necessary for the differential diagnosis of cytopenia, and the detection of hemophagocytosis in bone marrow is supportive of a diagnosis. However, it is not sensitive
440
Mayama et al
Hemophagocytic Lymphohistiocytosis
Mayama. Hemophagocytic Lymphohistiocytosis. Obstet Gynecol 2014.
enough to support a definitive diagnosis.1 Hemophagocytosis may not be found in initial biopsy samples, and yet it may linger in later biopsy samples.5 The pathogenesis of both genetic and acquired hemophagocytic lymphohistiocytosis is some form of impairment in the function of cytotoxic T lymphocytes and natural killer cells, although the exact mechanism is less clear for acquired hemophagocytic lymphohistiocytosis.1 Measuring levels of soluble interleukin-2 receptors (sCD25), which reflect the activation of T cells, and natural killer cell activity are more specific tests compared with other diagnostic criteria because these tests are based on the pathogenesis of hemophagocytic lymphohistiocytosis. Nevertheless, the utilization of these assays is limited because most medical centers cannot conduct these tests in their own hospitals. Therefore, clinicians should maintain a high level of suspicion of hemophagocytic lymphohistiocytosis in any patient with unexplained cytopenia and fever and should not delay treatment. This patient only met four of the eight criteria: fever; pancytopenia; hemophagocytosis in bone marrow; and a high level of ferritin on admission. The detection of a parvovirus B19 infection during the bone marrow biopsy indicated the virus associated with hemophagocytic lymphohistiocytosis was present in this case. Although a definitive diagnosis could not be made without measuring levels of soluble IL-2 receptors and natural killer cell activity, a test unavailable at our institution, we believed that the data we had were sufficient to make the diagnosis and begin therapy.1 Therefore, we started the administration of prednisolone promptly, which led to a favorable outcome for both mother and newborn.
OBSTETRICS & GYNECOLOGY
The main therapy used for hemophagocytic lymphohistiocytosis is suppression of exaggerated immune response through the use of immunosuppressive agents. A combined therapy of etoposide and dexamethasone, with or without intrathecal methotrexate and hydrocortisone, is recommended as a standard treatment in the HLA-94 protocol.6 However, corticosteroids or intravenous immune globulin are often used for hemophagocytic lymphohistiocytosis during pregnancy because of the risk of etoposide to the fetus, and these treatments have provided positive outcomes.7 Cyclosporine A is also an important treatment option. It was reported that cyclosporine A was effective in a corticosteroidsresistant case during pregnancy.5 Hemophagocytic lymphohistiocytosis is a rare disease, especially in cases involving pregnancies, so we do not have a standard treatment for cases during pregnancy. We have presented a case in which viral-associated hemophagocytic lymphohistiocytosis during pregnancy was successfully treated entirely through the administration of prednisolone. Prednisolone is classified as a category C by the U. S. Food and Drug Administration, and it can be inactivated in placenta.8 Prednisolone should be considered a treatment option for hemophagocytic lymphohistiocytosis during pregnancy.
REFERENCES
Early Hysteroscopic Removal of Intratubal Microinserts With Urologic Stone Retrieval Forceps
inserts used for hysteroscopic sterilization. Although early removal can be attempted hysteroscopically, hysteroscopic grasping forceps may be inadequate to grasp deeply positioned inserts.
Lisa M. Goldthwaite, MD, Lindsay Edwards, MD, PhD, and Kristina Tocce, MD, MPH BACKGROUND: Nickel hypersensitivity reactions can be an indication for the removal of intratubal microFrom the Division of Family Planning, Department of Obstetrics and Gynecology, University of Colorado Denver School of Medicine, Aurora, Colorado. Corresponding author: Lisa M. Goldthwaite, MD, University of Colorado Denver School of Medicine, Department of Obstetrics and Gynecology, 12631 E. 17th Avenue, Box B-198-2, Aurora, CO 80045; e-mail: lisa.goldthwaite@ ucdenver.edu. Financial Disclosures Kristina Tocce, MD, MPH, has served as a physician consultant for Conceptus and participated in the Bayer HeathCare Essure National Advisory Board Meeting in January 2014. The other authors did not report any potential conflicts of interest. © 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
VOL. 124, NO. 2, PART 2, AUGUST 2014
1. Roman LK, Gary JS. Secondary hemophagocytic lymphohistiocytosis in adults: an update on diagnosis and therapy. Clin Adv Hematol Oncol 2012;10:726–32. 2. Ishii E, Ohga S, Imashuku S, Yasukawa M, Tsuda H, Miura I, et al. Nationwide survey of hemophagaocytic lymphohistiocytosis in Japan. Int J Hematol 2007;86:58–65. 3. Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124–31. 4. Hejblum G, Lambotte O, Galicier L, Coppo P, Marzac C, Aumont C, et al. A web-based Delphi study for eliciting helpful criteria in the positive diagnosis of hemophagocytic syndrome in adult patients. PLos One 2014;9:e94024. 5. Yamaguchi K, Yamamoto A, Hisano M, Natori M, Murashima A. Herpes simplex virus 2-associated hemophagocytic lymphohistiocytosis in a pregnant patient. Obstet Gynecol 2005;105:1241–4. 6. Henter JI, Horne A, Arico M, Egeler RM, Elinder G, Filipovich AH, et al. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood 2002;100:2367–73. 7. Dunn T, Cho M, Medeiros B, Logan A, Ungewickell A, Liedtke M. Hemophagocytic lymphohistiocytosis in pregnancy: a case report and review of treatment options. Hematology 2012;17:325–28. 8. Murphy VE1, Fittock RJ, Zarzycki PK, Delahunty MM, Smith R, Clifton VL. Metabolism of synthetic steroids by the human placenta. Placenta 2007;28:39–46.
CASE: Three days after hysteroscopic sterilization, the patient presented with a rash consistent with a nickel hypersensitivity reaction. Ten days after placement, we successfully performed hysteroscopic removal of an intratubal microinsert with tri-prong urologic stone retrieval forceps after standard hysteroscopic grasping forceps was unable to reach the deeply positioned device. Within 36 hours of bilateral microinsert removal, all symptoms resolved. CONCLUSION: In difficult cases, 1-mm tri-prong urologic stone retrieval forceps can be useful for early hysteroscopic removal of intratubal microinserts. (Obstet Gynecol 2014;124:441–4) DOI: 10.1097/AOG.0000000000000338
T
he Essure system is a hysteroscopic sterilization system using intratubal microinserts consisting of an inner coil composed of stainless steel and polyethylene terephthalate fibers contained within an outer coil of nitinol (nickel and titanium).1 Approved for use by the U.S. Food and Drug Administration in 2002,
Goldthwaite et al
Hysteroscopic Microinsert Removal
441
in overwhelming infection and widespread hematogenous seeding. The rarity of clinical studies regarding abscess drainage in pregnancy makes recommendations regarding antibiotic coverage challenging, and empiric treatment in these patients has previously been suggested. The possible consequences of simple abscess drainage should not be underestimated in these patients, and close follow-up should be established to ensure clinical improvement.
Hemophagocytic Lymphohistiocytosis Associated With a Parvovirus B19 Infection During Pregnancy
CASE: We present a case of parvovirus B19 infection related to hemophagocytic lymphohistiocytosis during pregnancy. The patient experienced fever and pancytopenia. A bone marrow biopsy demonstrated hemophagocytosis and a giant proerythroblasts, which is characteristic of a parvovirus B19 infection. Viral serology for parvovirus B19 was positive. Prompt treatment was started because of the high level of certainty of viral-associated hemophagocytic lymphohistiocytosis, and the patient was successfully treated with prednisolone administration. She delivered a healthy newborn without any complications.
Michinori Mayama, MD, Masato Yoshihara, MD, Tetsuya Kokabu, MD, and Hidenori Oguchi, MD, PhD BACKGROUND: Hemophagocytic lymphohistiocytosis is potentially fatal. Prompt diagnosis and initiation of treatment are critical for ensuring the best possible prognosis.
REFERENCES 1. Kessous R, Barak A, Boaz S, Shteiner N, Moran-Gilad J, Weintraub A. Clinical and microbiological characteristics of Bartholin gland abscesses. Obstet Gynecol 2013;122:794–9. 2. Lopez-Zeno J, Ross E, O’Grady J. Septic shock complicating drainage of a Bartholin gland abscess. Obstet Gynecol 1990;76:915–6. 3. Luppi P. How immune mechanisms are affected by pregnancy. Vaccine 2003;21:3352–7. 4. Barton JR, Sibai BM. Severe sepsis and septic shock in pregnancy. Obstet Gynecol 2012;120:689–706. 5. Womack J. Septic arthritis of the sternoclavicular joint. J Am Board Fam Med 2012;25:908–12. 6. Ross JJ, Shamsuddin H. Sternoclavicular septic arthritis: review of 180 cases. Medicine 2004;83:139–48.
CONCLUSION: Hemophagocytic lymphohistiocytosis should be considered when encountering unexplained cytopenia and fever. Prednisolone was an effective treatment. (Obstet Gynecol 2014;124:438–41) DOI: 10.1097/AOG.0000000000000385
From the Department of Obstetrics, Perinatal Medical Center, Toyota Memorial Hospital, Toyota, Aichi, Japan. The authors thank Shinichi Mizuno for his knowledge of hemophagocytic lymphohistiocytosis, and Yasuyuki Kishigami for checking our manuscript and providing constructive comments from preparation to revision. Corresponding author: Michinori Mayama, 20-2, Misato-cho, Toyota, Aichi, Japan; e-mail: [email protected]. © 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
438
Mayama et al
Hemophagocytic Lymphohistiocytosis
H
emophagocytic lymphohistiocytosis is a rare disorder characterized by systemic benign proliferation of histiocytes in a hyperinflammatory state and phagocytosis of hematopoietic elements. Hemophagocytic lymphohistiocytosis can be classified according to the underlying etiology into either familial or acquired forms. Familial hemophagocytic lymphohistiocytosis often occurs during infancy and early childhood, and
OBSTETRICS & GYNECOLOGY
it is associated with an autosomal recessive inheritance pattern in most cases. Acquired hemophagocytic lymphohistiocytosis generally occurs in older children and adults who have no known genetic causes or family history, and it is associated with various infectious, malignant, metabolic, and rheumatologic conditions.1 The major signs and symptoms of hemophagocytic lymphohistiocytosis are fever, hepatosplenomegaly, and cytopenia in at least two cell lines. Less frequently observed symptoms are rash, lymphadenopathy, icterus, and neurologic symptoms. Hemophagocytic lymphohistiocytosis is potentially fatal, and early initiation of treatment is necessary for the best possible prognosis. However, establishing a diagnosis quickly is often challenging because of the nonspecific symptoms of hemophagocytic lymphohistiocytosis. Hemophagocytic lymphohistiocytosis is a rare disorder, especially in cases involving pregnancies. A nationwide survey in Japan reported that among 567 patients with hemophagocytic lympohistiocytosis, 301 cases (53.1%) were related to infection.2 In the infection-associated cases, Epstein–Barr virus is a predominant cause (163 cases, 54.2%), and only three cases (1.0%) were caused by parvovirus B19.2
CASE A 28-year-old woman, gravida 2 para 2, at 20 1/7 weeks of gestation with a 3-day history of fatigue, dizziness, and fever was admitted to the hospital. Pancytopenia was detected at the hospital, and the patient was then transferred to our hospital. Mild anemia had been detected in the patient during the first trimester and was managed with oral iron therapy. She had not been experiencing any other complications during this pregnancy. On admission, her vital signs were as follows: temperature 38.1˚C; blood pressure 101/50 mm Hg; and heart rate 111 beats per minute. No symptoms of significant swelling of superficial lymph nodes, hepatomegaly, or splenomegaly were observed during the physical examination. Initial laboratory results showed pancytopenia with a hemoglobin level of 4.2 g/dL, a white blood cell count of 600/microliter (neutrophils 44%, lymphocytes 39%, monocytes 11%), and a platelet count of 83,000/
Box 1. Diagnostic Criteria for Hemophagocytic Lymphohistiocytosis3 Molecular diagnosis of hemophagocytic lymphohistiocytosis or the presence of at least five of eight criteria: 1. Fever 2. Splenomegaly 3. Cytopenia (affecting at least two lineages in the peripheral blood) Hemoglobin less than 9.0 g/dL, platelets less than 100,000/microliter, neutrophils less than 1,000/ microliter 4. Hypertriglyceridemia or hypofibrinogenia Fasting triglycerides 3.0 mmol/L or more (265 mg/dL or more), fibrinogen 1.5 g/L or less 5. Hemophagocytosis in bone marrow, spleen, or lymph nodes 6. Low or absent natural killer cell activity 7. Ferritin 500 ng/mL or more 8. Soluble CD25 (soluble interleukin-2 receptor) 2,400 units/mL or more Modified from Henter JI, Horne A, Arico´ M, Egeler RM, Filipovich AH, Imashuku S. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124–31. Copyright 2006 Wiley-Liss, Inc.
microliter. An elevation of lactate dehydrogenase 277 international units/L (119–229 international units/L) and serum ferritin 1,269.2 ng/mL (5.0–177.6 ng/mL) were observed, but her liver and kidney function test results, plasma electrolytes, and coagulation status were all within normal limits. An ultrasonography revealed no evidence of fetal distress or fetal hydrops. A bone marrow biopsy detected increased numbers of histiocytes engulfing erythroid precursors, as well as neutrophils and platelets. Giant proerythroblasts, which are characteristic of parvovirus B19 infections, were also detected (Fig. 1A and 1B). Hemophagocytic syndrome associated with a parvovirus B19 infection was suspected. We began the administration of prednisolone in 40-mg daily dosages. The patient received a transfusion with 4 units of red blood cells to treat severe anemia. Her red blood cell, white blood cell, and platelet counts began to recover, so we started tapering prednisolone dosages
Fig. 1. Bone marrow biopsy revealed histiocytes with hemophagocytosis (A) and giant proerythroblast (B). Mayama. Hemophagocytic Lymphohistiocytosis. Obstet Gynecol 2014.
A
VOL. 124, NO. 2, PART 2, AUGUST 2014
B
Mayama et al
Hemophagocytic Lymphohistiocytosis
439
40mg
30mg 20mg
15mg
20mg Prednisolone
25
20
WBC (x 103 μL)
15
Hemoglobin (g/dL) Platelets (x 104 μL)
10
Fig. 2. Clinical course. Medication dosages and changes in white blood cells (WBC), hemoglobin, and platelets are shown.
5
0
0
1
5
20
40
60
84
100
124
Days post admission
gradually on hospital day 5 (Fig. 2). Additional serological test results showed parvovirus B19 antibody titers of immunoglobulin M and immunoglobulin G of 9.10 and 7.25; 2 weeks later, they were 9.88 and 8.48 (normal range less than 0.79 and less than 0.79). Viral serology tests for Epstein–Barr virus and cytomegalovirus were negative. These results confirmed the diagnosis of hemophagocytic lymphohistiocytosis associated with parvovirus B19 infection. During the remainder of her pregnancy, excellent disease management was maintained without fetal distress or fetal growth restriction. At 37 4/7 weeks of gestation, she delivered a 2,876-g male newborn by normal vaginal delivery with Apgar scores of 9 and 10 at 1 minute and 5 minutes, respectively.
COMMENT Early diagnosis of hemophagocytic lymphohistiocytosis and prompt initiation of treatment are essential because delaying therapy may lead to irreversible multiple organ failure. The diagnostic criteria of hemophagocytic lymphohistiocytosis are listed in Box 1. These criteria have been widely used; however, other diagnostic criteria, especially for acquired hemophagocytic lymphohistiocytosis in adults, are necessary because these criteria were mainly composed using the data of familial hemophagocytic lymphohistiocytosis in pediatric cases.4 Timely diagnosis is often challenging because of the nonspecific clinical presentations of hemophagocytic lymphohistiocytosis. Bone marrow biopsy is necessary for the differential diagnosis of cytopenia, and the detection of hemophagocytosis in bone marrow is supportive of a diagnosis. However, it is not sensitive
440
Mayama et al
Hemophagocytic Lymphohistiocytosis
Mayama. Hemophagocytic Lymphohistiocytosis. Obstet Gynecol 2014.
enough to support a definitive diagnosis.1 Hemophagocytosis may not be found in initial biopsy samples, and yet it may linger in later biopsy samples.5 The pathogenesis of both genetic and acquired hemophagocytic lymphohistiocytosis is some form of impairment in the function of cytotoxic T lymphocytes and natural killer cells, although the exact mechanism is less clear for acquired hemophagocytic lymphohistiocytosis.1 Measuring levels of soluble interleukin-2 receptors (sCD25), which reflect the activation of T cells, and natural killer cell activity are more specific tests compared with other diagnostic criteria because these tests are based on the pathogenesis of hemophagocytic lymphohistiocytosis. Nevertheless, the utilization of these assays is limited because most medical centers cannot conduct these tests in their own hospitals. Therefore, clinicians should maintain a high level of suspicion of hemophagocytic lymphohistiocytosis in any patient with unexplained cytopenia and fever and should not delay treatment. This patient only met four of the eight criteria: fever; pancytopenia; hemophagocytosis in bone marrow; and a high level of ferritin on admission. The detection of a parvovirus B19 infection during the bone marrow biopsy indicated the virus associated with hemophagocytic lymphohistiocytosis was present in this case. Although a definitive diagnosis could not be made without measuring levels of soluble IL-2 receptors and natural killer cell activity, a test unavailable at our institution, we believed that the data we had were sufficient to make the diagnosis and begin therapy.1 Therefore, we started the administration of prednisolone promptly, which led to a favorable outcome for both mother and newborn.
OBSTETRICS & GYNECOLOGY
The main therapy used for hemophagocytic lymphohistiocytosis is suppression of exaggerated immune response through the use of immunosuppressive agents. A combined therapy of etoposide and dexamethasone, with or without intrathecal methotrexate and hydrocortisone, is recommended as a standard treatment in the HLA-94 protocol.6 However, corticosteroids or intravenous immune globulin are often used for hemophagocytic lymphohistiocytosis during pregnancy because of the risk of etoposide to the fetus, and these treatments have provided positive outcomes.7 Cyclosporine A is also an important treatment option. It was reported that cyclosporine A was effective in a corticosteroidsresistant case during pregnancy.5 Hemophagocytic lymphohistiocytosis is a rare disease, especially in cases involving pregnancies, so we do not have a standard treatment for cases during pregnancy. We have presented a case in which viral-associated hemophagocytic lymphohistiocytosis during pregnancy was successfully treated entirely through the administration of prednisolone. Prednisolone is classified as a category C by the U. S. Food and Drug Administration, and it can be inactivated in placenta.8 Prednisolone should be considered a treatment option for hemophagocytic lymphohistiocytosis during pregnancy.
REFERENCES
Early Hysteroscopic Removal of Intratubal Microinserts With Urologic Stone Retrieval Forceps
inserts used for hysteroscopic sterilization. Although early removal can be attempted hysteroscopically, hysteroscopic grasping forceps may be inadequate to grasp deeply positioned inserts.
Lisa M. Goldthwaite, MD, Lindsay Edwards, MD, PhD, and Kristina Tocce, MD, MPH BACKGROUND: Nickel hypersensitivity reactions can be an indication for the removal of intratubal microFrom the Division of Family Planning, Department of Obstetrics and Gynecology, University of Colorado Denver School of Medicine, Aurora, Colorado. Corresponding author: Lisa M. Goldthwaite, MD, University of Colorado Denver School of Medicine, Department of Obstetrics and Gynecology, 12631 E. 17th Avenue, Box B-198-2, Aurora, CO 80045; e-mail: lisa.goldthwaite@ ucdenver.edu. Financial Disclosures Kristina Tocce, MD, MPH, has served as a physician consultant for Conceptus and participated in the Bayer HeathCare Essure National Advisory Board Meeting in January 2014. The other authors did not report any potential conflicts of interest. © 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
VOL. 124, NO. 2, PART 2, AUGUST 2014
1. Roman LK, Gary JS. Secondary hemophagocytic lymphohistiocytosis in adults: an update on diagnosis and therapy. Clin Adv Hematol Oncol 2012;10:726–32. 2. Ishii E, Ohga S, Imashuku S, Yasukawa M, Tsuda H, Miura I, et al. Nationwide survey of hemophagaocytic lymphohistiocytosis in Japan. Int J Hematol 2007;86:58–65. 3. Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124–31. 4. Hejblum G, Lambotte O, Galicier L, Coppo P, Marzac C, Aumont C, et al. A web-based Delphi study for eliciting helpful criteria in the positive diagnosis of hemophagocytic syndrome in adult patients. PLos One 2014;9:e94024. 5. Yamaguchi K, Yamamoto A, Hisano M, Natori M, Murashima A. Herpes simplex virus 2-associated hemophagocytic lymphohistiocytosis in a pregnant patient. Obstet Gynecol 2005;105:1241–4. 6. Henter JI, Horne A, Arico M, Egeler RM, Elinder G, Filipovich AH, et al. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood 2002;100:2367–73. 7. Dunn T, Cho M, Medeiros B, Logan A, Ungewickell A, Liedtke M. Hemophagocytic lymphohistiocytosis in pregnancy: a case report and review of treatment options. Hematology 2012;17:325–28. 8. Murphy VE1, Fittock RJ, Zarzycki PK, Delahunty MM, Smith R, Clifton VL. Metabolism of synthetic steroids by the human placenta. Placenta 2007;28:39–46.
CASE: Three days after hysteroscopic sterilization, the patient presented with a rash consistent with a nickel hypersensitivity reaction. Ten days after placement, we successfully performed hysteroscopic removal of an intratubal microinsert with tri-prong urologic stone retrieval forceps after standard hysteroscopic grasping forceps was unable to reach the deeply positioned device. Within 36 hours of bilateral microinsert removal, all symptoms resolved. CONCLUSION: In difficult cases, 1-mm tri-prong urologic stone retrieval forceps can be useful for early hysteroscopic removal of intratubal microinserts. (Obstet Gynecol 2014;124:441–4) DOI: 10.1097/AOG.0000000000000338
T
he Essure system is a hysteroscopic sterilization system using intratubal microinserts consisting of an inner coil composed of stainless steel and polyethylene terephthalate fibers contained within an outer coil of nitinol (nickel and titanium).1 Approved for use by the U.S. Food and Drug Administration in 2002,
Goldthwaite et al
Hysteroscopic Microinsert Removal
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