What Is the Differential Diagnosis of White Vulvar Lesions?

Patient Presentation
An 11-year-old healthy female came to clinic after having noticing a “bump” in her vaginal area after taking a shower. Her mother was uncertain what it was and so had made the appointment. She denied having any significant pain, itching, discharge or actual bleeding. She was premenarchal. She had normal bowel movements and urination. She denied any trauma to the area or potential sexual abuse. The past medical and family histories, and review of systems were non-contributory.

The pertinent physical exam showed a healthy female with normal vital signs who was tracking at the 75-90% for growth parameters. Her abdominal and spine exams were normal. Her genitourinary examination showed a small slightly elevated hematoma at the posterior fourcette. Areas of the labia major and minora looked to have thinned tissue and there was hypopigmentation that was linear around the edges of the labia minora and which extended along the center of the perineal body. There was some minor erythema of the areas around the hypopigmentation. There were other areas of hypopigmentation that were 3-5 mm in size on the labia majora and minora. The hymen was intact and the tissues and anatomy otherwise appeared normal.

The diagnosis of possible lichen sclerosis et atrophicus (LSA) was made. In retrospect, she said that she had had some pruritus in her genital area for the past few days and had been itching the area more. Pictures were taken for the medical record. The pediatrician checked the medical literature which recommended strong steroid treatment but possibly biopsy before treatment, so gynecology was consulted. They agreed that this was LSA and recommended steroid use without a biopsy. They would see the patient in about 3-4 weeks for followup.

Discussion
Lichen sclerosis et atrophicus (LSA) is a chronic inflammatory disease with a strong autoimmune association but its cause is unknown. Usually seen in middle-aged women (40-60 years), it can occur in females and males of all ages, but prepubertal females are more common in the pediatric age group. Treatment includes stronger steroid medications or anti-inflammatory medications and pediatric patients usually have resolution with time. The classic presentation of LSA are genital lesions that are hypopigmentation in an hour-glass or a figure of 8 distribution for females as it involves the vulva, perineum and anal areas. Tissues appear thinned and there can be some erythema as well. Patients can be asymptomatic, have some pruritus or pain. Extra genital lesions can also be seen. A review of LSA can be found here

Learning Point
The differential diagnosis of white vulvar lesions includes:

  • Hypopigmentation
    • Normal variant
    • Post-inflammatory including general vulvovaginitis
    • Vitiligo
  • Angioedema
  • Atopic dermatitis
  • Psoriasis
  • Seborrheic dermatitis
  • Lichen sclerosis et atrophicus
  • Lichen planus
  • Lichen simplex chronicus
  • Morphea or localized sclerosis
  • Mycosis, ex. tinea versicolor
  • Ulcer
  • Lipschultz
  • Herpes simplex
  • Syphilis
  • Other infections
  • Trauma
    • Scratching
    • Tight clothing
    • Burn
    • Sexual assault
  • Systemic autoimmune
    • Bechet’s
      Scleroderma
  • Malignancies – very rare
    • Basal cell carcinoma
    • Squamous cell carcinoma
    • Leukemia/lymphoma
  • Xanthoma

    Questions for Further Discussion
    1. What is a Lipschultz ulcer? A review can be found here
    2. How are straddle injuries treated? A review can be found here
    3. What are some presentations for child sexual abuse? A review can be found here

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for these topics: Vulvar Disorders and Skin Conditions.

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    To view videos related to this topic check YouTube Videos.

    Resende FS, Conforti C, Giuffrida R, de Barros MH, Zalaudek I. Raised vulvar lesions: be aware! Dermatol Pract Concept. 2018;8(2):158-161. doi:10.5826/dpc.0802a16

    Charamanta M, Soldatou A, Michala L. Vulvar Ulcers in Children: Dramatic But Self-Limited. Pediatric Emergency Care. 2021;37(2):70. doi:10.1097/PEC.0000000000002004

    Orszulak D, Dulska A, Nizinski K, et.al. Pediatric Vulvar Lichen Sclerosus – A Review of the Literature. Int J. Environ. Res. Public Health. 2021:18;7153.

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa

  • How is Cyclic Vomiting Syndrome Treated?

    Patient Presentation
    A 13-year-old female came to clinic after a 12 hour emergency room visit for severe emesis, nausea, headache and abdominal pain 2 days previously. She had about 2 hours of nausea, milder abdominal pain and headache that was frontal with radiation to bilateral temples. She had no photophobia or phonophobia. She then began to have multiple episodes of emesis over the next 2-3 hours and her nausea, headache and abdominal pain became worse. After another 4 hours, she began to feel better and was much improved after sleeping. The emergency room diagnosed her with a severe migraine as she didn’t have or develop any infectious symptoms and her laboratory testing showed electrolytes that were consistent with emesis and dehydration. Her abdominal and head computed tomographic studies were negative. The first day after the emergency room visit she was more tired, but in the office she and her mother deny any problems. The past medical history showed that she had some intermittent headaches and these mainly occurred with illnesses or with poor sleep. She had started her menses about 7 months previously and they were intermittent. The family history is strongly positive for migraines on the maternal side including her mother, older sister and maternal aunt. This maternal aunt’s daughter has cyclic vomiting syndrome, and her other son had migraines.

    The pertinent physical exam showed normal vital signs and her weight was back to her pre-emesis weight. Her examination was unremarkable.

    The diagnosis of a likely first migraine was made. Her mother had many questions about potential treatment and also cyclic vomiting syndrome. “They only recently diagnosed her cousin with the cyclic vomiting after a long time having lots of problems. They are looking at my nephew too. I just want to be proactive about this if she is going to have a lot more problems,” her mother stated. The pediatrician acknowledged the mother and patient’s concerns by saying, “With this family history we’ll need to be really aware. Maybe you’ll never have another episode like this one, but we need to start keeping track of the symptoms early on, so we can see if there are any patterns. If you have more it may be migraine but it could be cyclic vomiting. I’m going to go over using a symptom diary. It’s an important part of the evaluation for these types of problems. It’s just like keeping track of sugar measurements for people with diabetes. It helps us figure out problems and how to treat them. Also treatment for migraines and cyclic vomiting is similar. Healthy lifestyle changes like making sure you have consistent sleep, exercise, and don’t get dehydrated are really important. If you have more episodes we can talk about maybe starting a medicine to prevent them. If you start to feel that nausea, headache or abdominal pain again, then you can use a medicine to try to stop it before it starts like your mom does. It’s called a triptan and I’ll go over how to use it,” she counseled.

    The patient’s clinical course showed another episode in the next 4 months that responded to triptan use and did not require an emergency room visit.

    Discussion
    Cyclic vomiting syndrome (CVS) “…is characterized by episodic attacks of intense nausea and emesis, with predictably cyclic timing of episodes, and complete resolution of symptoms between attacks.” It can be very difficult to diagnose and likely is underreported. Incidence is thought to be around 3.5/1000,000 persons. There are four phases to the clinical syndrome:

    • Prodromal phase is often brief (1-2 hours) where patients can have intensive nausea, abdominal pain, pallor and tiredness
      • Other symptoms may include headache, mood changes, phono- or photophobic, yawning, and systemic autonomic nervous symptoms. These can continue through the vomiting and recovery phases as well.
    • Vomiting phase
      • Lasts usually hours
      • First hour has the most emesis (6+ times) that usually wanes over the next 4-8 hours
      • May need intravenous hydration in many cases or hospitalizations
    • Recovery phase begins with when the nausea remits and continues until the patient has recovered their appetite, body weight lost during vomiting phase and strength. Patients usually sleep during this period. This is also usually a brief period of about 6 hours, but symptoms can linger for up to 1 week.
    • Interepisodic phase where patients are symptom free

    It can be difficult to tell if the episodes are recurrent emesis or an episodic attack. While the symptoms patients experience and the timing and duration are different, they are often stereotypical for an individual patient. “Attacks can last from hours to days (between 1h and 10 days, mean 2 days). Typically, attacks have a predictable periodicity…[and t]his periodicity is the discriminating criterion for …classification [as CVS]. This periodicity is variable for each patient.”

    Symptom absence between episodes is also a key feature.
    Some patients may be able to recognize potential triggers such as lack of sleep, exercise, excitement/stress, menstruation, and potentially certain foods (i.e. cheeses, chocolate, acidic or salty foods).
    Natural history is that symptoms may resolve within 10 years (about 60% of children). About 50% go on to have a migraine syndrome. CVS is thought to be linked to migraine by several mechanisms mainly as both are primary brain disorders. The differential diagnosis of CVS includes:

    • Central nervous system
      • Migraine
      • Epilepsy/seizure
      • Intracranial masses
      • Cannabis-induced hyperemesis syndrome
      • Autonomic dysfunction
    • Gastrointestinal
      • Gastroesophageal reflux disease
      • Obstruction
      • Inflammatory bowel disease
      • Celiac disease
      • Cholecystitis
      • Peptic ulcer disease
    • Metabolic
      • Inborn errors of metabolism
      • Mitochondrial disease gastrointestinal problems including gastroesophageal reflux disease, obstruction, inflammatory bowel disease
    • Renal
        Hydronephrosis

    If the patient does not have resolution of their symptoms between attacks or has other central nervous system (CNS) problems such as developmental or intellectual problems, seizures, evidence of encephalopathy, or it appears that the attacks may precipitate CNS problems, or that there are additional gastrointestinal symptoms (i.e. gastrointestinal bleeding) then these are red flags that should be evaluated.

    Learning Point
    Treatment for CVS includes:

    • Lifestyle changes – consistent food and fluid intake, sleep, and exercise
    • Interepisodic phase
      • Prophylactic medication for those that are severe (> 2 day duration, hospitalization) or frequent (> every 4-6 weeks)
      • < 5 years old = cyproheptadine
      • > 5 years old = amitriptyline. This is the most effective agent overall
      • Consider propranolol as second line
      • There are other options if these are not tolerated or give insufficient control
    • Prodromal phase
      • Triptans used as an abortive medication – sumatriptan, rizatriptan, zolmitripan
      • Benzodiazepines may be helpful for panic anxiety or anticipation of vomiting phase
    • Vomiting phase
      • Intravenous fluids with glucose to provide energy
      • Intravenous, rectal or dermal formulations of
        • Antiemetics – ondanstron, granisetron
        • Analgesics – ketorolac
        • Sedatives – z, diphenhydramine
      • Environment that is dark, quiet
    • Recovery phase
      • Management of symptoms as needed

    Questions for Further Discussion
    1. Explain the physiology that causes emesis? A review can be found here
    2. What are different types of headaches? A review can be found here
    3. What causes vomiting? A review can be found here

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for these topics: Nausea and Vomiting and Migraine.

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    To view videos related to this topic check YouTube Videos.

    Donnet A, Redon S. Cyclic Vomiting Syndrome in Children. Curr Pain Headache Rep. 2018;22(4):30. doi:10.1007/s11916-018-0684-6

    Li BUK. Managing cyclic vomiting syndrome in children: beyond the guidelines. Eur J Pediatr. 2018;177(10):1435-1442. doi:10.1007/s00431-018-3218-7

    Kovacic K, Li BUK. Cyclic vomiting syndrome: A narrative review and guide to management. Headache. 2021;61(2):231-243. doi:10.1111/head.14073

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa

    How Effective are Rotavirus Vaccines?

    Patient Presentation
    A 15-month-old male came to the emergency room because of diarrhea for < 24 hours that was not improving, fever to 100.8°F and fatigue. He had loose, watery non-bilious, non-mucous stools that would come out of his diapers. He had been trying to drink and had not vomited but was taking less and less orally over the day. His father was not able to tell when his last urine was because of the diarrhea. "There was an email yesterday that the daycare had another child with rotavirus," he offered.

    The past medical history showed he had two ear infections and several viral infections including a documented influenza infection. Record review noted he was vaccinated for some diseases but not rotavirus.

    The pertinent physical exam showed a very tired appearing male who was curled up in his father’s lap. He was alert and could cry appropriately but without tears. His vital signs showed heart rate of 106 beats/minute, blood pressure of 86/52, temperature of 100.5°F, and weight of 11.25 kg which was down from 12.36 kg in a visit the week before in his physician’s office. His mucous membranes were tacky and his capillary refill was > 3 seconds. His abdomen seemed overall slightly diffusely tender but without guarding, masses or organomegaly.

    The diagnosis of acute gastroenteritis with dehydration was made. Two emergency room professionals felt that the smell of the diarrhea was consistent with rotavirus based on their past clinical experience. The work-up included starting an IV and drawing blood that was consistent with pre-renal dehydration. He started to appear somewhat better after his second IV fluid bolus, and after the third one, he started to drink some. His abdominal pain also seemed to improve. He was monitored in the emergency room overnight, and while he had more diarrhea, he started to have more free urine output and was drinking well before discharge.

    Discussion
    Rotaviruses (RV) are a leading cause of severe, acute, dehydrating diarrhea for children particularly those under age 5 years globally. As RVs are highly contagious and in the pre-RV era they caused an estimated 30-50% of hospitalizations for gastroenteritis yearly or about 111 million cases yearly. They also caused an estimated 500,000/year pediatric deaths.

    RV are double-stranded RNA viruses of the genus Rotavirus. There are 11 species with type A being the most common cause of acute gastroenteritis. RV is transmitted mainly through the oral-fecal and hand-to-hand routes with the gastrointestinal system being the primary site of infection. Incubation is only 16-18 hours. RV is excreted in the feces in massive amounts for 5-7 days, but only a few particles (10-100) can cause infection. RV is also “…highly resistant to environmental factors, including temperature and pH, which enhances their infectious potential.”

    Clinical symptoms include non-bloody (usually) diarrhea, and can also include nausea, emesis, and abdominal pain. Electrolyte imbalance and dehydration can easily occur because of multiple loose or liquid stools that can be smaller or voluminous. Dehydration itself obviously can have its own severe consequences which as noted above can cause significant morbidity and mortality. Systemic symptoms such as fever, and fatigue are common. The diarrhea occurs through osmotic, secretory and neurogenic pathways. Laboratory testing is consistent with a limited inflammatory response. Other systemic problems can occur through viremia and antigenemia including seizures and other central nervous system disease, biliary atresia, lower respiratory tract infections, and there appears to be a role in autoimmunity including Celiac disease, and Diabetes mellitus type 1. Disease does protect against subsequent infections, but remember there are more than 1 species. While the majority of infections occur in those under age 5, it can still occur in older ages.

    Learning Point
    RV vaccine introduction has been an extraordinary global public health achievement. RV vaccination is recommended for young children globally since 2006. The timing and number of doses depends on the particular vaccine, with most starting after 6 weeks of age. These are live-attenuated vaccines which are highly effective in reducing the proportion of RV associated acute gastroenteritis by 50% overall globally, with also a concurrent significant reduction in mortality. Estimates of effectiveness are around 90%, 80% and 40-50% for high, middle and low-mortality countries depending on the specific vaccine. This heterogeneity of effectiveness is based on country with more occurring in lower to mid- mortality countries and is likely multifactorial including nutritional status, co-infections, microbiome, maternal antibiotics and co-administration of polio vaccine.

    Potential common vaccine adverse effects include appetite loss, fussiness, diarrhea, abdominal pain, emesis, fever and weakness. Overall safety is excellent with current vaccines. In 1999, the first RV vaccine RotaShield was withdrawn because of increased risk of intussception which has not been seen with subsequent RV vaccines.

    Questions for Further Discussion
    1. How is Norovirus similar to Rotavirus? A review can be found here
    2. What is the physiology of vomiting? A review can be found here
    3. What causes abdominal pain? A review can be found here

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for these topics: Rotavirus Infections and Diarrhea.

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    To view videos related to this topic check YouTube Videos.

    Caddy S, Papa G, Borodavka A, Desselberger U. Rotavirus research: 2014-2020. Virus Res. 2021;304:198499. doi:10.1016/j.virusres.2021.198499

    Cates JE, Tate JE, Parashar U. Rotavirus vaccines: progress and new developments. Expert Opin Biol Ther. 2022;22(3):423-432. doi:10.1080/14712598.2021.1977279

    Karolina Pawluszkiewicz, Ryglowski PJ, Idzik N, et al. Rotavirus Infections: Pathophysiology, Symptoms, and Vaccination. Pathogens. 2025;14(5):480. doi:10.3390/pathogens14050480

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa

    When Do You Transfuse?

    Patient Presentation
    A 5-year-old female came to clinic with a fever for 2-3 days with rhinorrhea but no cough. Her fever was up to 101.2F and was responsive to antipyretics. She was tired, but was playing and generally acting normal, except for eating slight less. She was drinking and urinating well. A variety of community viruses and streptococcal sore throat were circulating.

    The past medical history and family history was non-contributory. The review of systems was negative for cough, emesis or nausea, diarrhea, changes in urine or stool. There were no rashes.

    The pertinent physical exam showed a tired appearing female who was very conversant and interactive. Her vital signs showed a pulse of 78/minute, blood pressure of 94/68, respiratory rate of 18 per minute, temperature of 37.4C and pulse oximeter of 98% on room air. HEENT showed some clear rhinorrhea, slightly thickened tympanic membranes without erythema or bulging, her tonsils were 2+ bilaterally and her throat had no erythema. Her heart was regular rate and rhythm with a grade II/V musical systolic murmur best at lower left sternal border. Lungs were clear. She didn’t like her abdomen examined but her liver seemed to be slightly enlarged, but no other obvious masses or splenomegaly. There was no costovertebral angle or suprapubic tenderness. She had 1 anterior cervical node that was 1 cm and a few other shotty nodes. She also had a few shotty inguinal nodes. There were no other lymph nodes palpated on her head, supraclavicular, axillary, epitrochlear or popliteal areas. She had no skin rashes, but her skin overall had a distinctly grayer appearance. She had extremely pale oral and conjunctival mucosa, conjunctiva, and very pale palms.

    The diagnosis of of a clinically significant anemia and a differential diagnosis consistent with it was made. The laboratory evaluation of a complete metabolic profile showed slightly elevated AST and ALT, but normal uric acid and lactate dehydrogenase. Her complete blood count was significant for a hemoglobin of 4.1 g/dL, hematocrit of 14%, white blood cell count of 3.5 x 1000/mm2 and platelets of 210 x 1000/mm2. The general pediatrician remembered that < 5 g/dL usually needed to be transfused in addition to this patient needing further evaluation for the cause of the severe anemia. The hematologist agreed and the patient was admitted. The differential and blood smear came back as probable leukemia which was later confirmed. The patient received red blood cell transfusions, antibiotics potential infectious diseases and was discharged after workup and induction chemotherapy.

    Discussion
    While modern science, especially in pharmaceuticals, has made tremendous therapies available, blood and blood products continue to be a “…finite and limited resource that must be used wisely….” Blood banking and transfusion guidelines and procedures continue to maintain and improve a safe system for blood product use, which has made significant improvements in patient mortality and morbidity.

    As with any treatment there are potential risks and blood products carry some unique ones as they are biological agents. Some potential risks of transfusion include:

    • Hemolytic reactions, acute and delayed
    • Infection
    • Electrolyte problems
    • Cardiovascular overload
    • Acute lung injury

    Transfusion related risks can be reduced by using blood products that have leukoreduction (decreasing the numbers of residual leukocytes if the end product is not leukocytes), irradiation (kills residual potentially viable leukocytes and infectious organisms), and washing (removes plasma proteins and additives such as glycerol), ABO blood group antigen matching, and volume reduction.
    These are important, but probably more important is transfusion stewardship where systems of care can help to reduce the need for transfusions. Some of these include:

    • Use of guidelines for indications for transfusion
    • Performing the minimal phlebotomy needed for clinical care including not initiating or discontinuation of “routine” tests, and asking how will the test results assist in clinical care before ordering them
    • Using smaller phlebotomy tubes (i.e. neonatal collection tubes) so less blood is needed to perform the test
    • Using point of care testing devices
    • Delayed cord clamping at birth
    • Removal of sampling lines early
    • Iron supplementation if appropriate
    • Use of surgical interventions such as cell salvage or antifibrinolytics

    Learning Point

    • Red blood cells
      • Goal is to correct the anemia to provide hemostability and adequate oxygen carrying capacity and tissue perfusion.
      • Main indications:
        • Acute or chronic anemia
        • Hemoglobin variant complication prevention
        • Bleeding/Hemorrhage – if hemodynamically unstable then multiple blood products are recommended including red blood cells, plasma and platelets
      • Transfusion for anemia centers mainly on 3 questions:
        • Is the child hemodynamically stable? If not, then transfusion should be considered based on clinical judgement
        • Are there special circumstances to consider such as patient is a neonate, has oncological disease or congenital heart disease, etc.?
        • What is the hemoglobin?
          • < 5 g/dL transfusion is recommended
          • 5-7 g/dL transfusion may be recommended based on clinical judgement
          • > 7 g/dL and hemodynamically unstable – may be recommended based on clinical judgement
          • > 7 g/dL and hemodynamically stable – generally transfusion is not recommended but will depend on clinical scenario and clinical judgement
        • Amount to transfuse is often 10-15 ml/kg/transfusion, but will depend on clinical scenario.
    • Platelets
      • Goal is to stop or prevent bleeding
      • Main indications
        • Bleeding/hemorrhage
        • Risk for bleeding such as procedures
        • Congenital platelet abnormalities
      • Generally transfused when platelet count is < 10 x 109g/dL, but this may differ significantly depending on the clinical scenario such as oncology patients or those with a high risk of intracranial hemorrhage using higher platelet counts as a threshold.
      • Amount to transfuse is often 10-15 ml/kg/transfusion, but will depend on clinical scenario.
    • Other blood products
      • Plasma
        • Main indications
        • Bleeding/hemorrhage
        • Coagulation profile correction
      • Granulocyte transfusions
        • Main indication is severe or prolonged neutropenia
      • Cryoprecipitate
        • Main indications
          • Fibrinogen replacement
          • Also used as source of Factor XIII, Factor VIII and von Willebrand factor before pharmacological factor concentrates

    Questions for Further Discussion
    1. What is the differential diagnosis of anemia? A review can be found here
    2. How does acute leukemia present? A review can be found here
    3. What are the clotting factors? A review can be found here

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for these topics: Blood Transfusion , Anemia and Leukemia.

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    To view videos related to this topic check YouTube Videos.

    Valentine SL, Bembea MM, Muzynski JA, et al. Consensus recommendations for RBC transfusion practice in critically ill children from the pediatric critical care transfusion and anemia expertise initiative. Pediatr Crit Care Med 2018:19(9):884-98.

    Maw G, Furyk C. Pediatric Massive Transfusion: A Systematic Review. Pediatric Emergency Care. 2018;34(8):594. doi:10.1097/PEC.0000000000001570

    Nellis ME, Goel R, Karam O. Transfusion Management in Pediatric Oncology Patients. Hematology/Oncology Clinics of North America. 2019;33(5):903-913. doi:10.1016/j.hoc.2019.05.011

    Mo YD, Delaney M. Transfusion in Pediatric Patients. Clinics in Laboratory Medicine. 2021;41(1):1-14. doi:10.1016/j.cll.2020.10.001

    Chapman M, Keir A. Patient Blood Management in Neonates. Clinics in Perinatology. 2023;50(4):869-879. doi:10.1016/j.clp.2023.07.004

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa