Scurvy: Not Lost in History

1
Scurvy Not Lost in History

• Dorothy Dow, MD
• Betty Del Rio Rodriguez, MD
• With special thanks to Dr. Janet F. Williams, MD
• UT Health Science Center San Antonio

2
Abstract

• Scurvy, a disease of Vitamin C deficiency, was
  appreciated in the Renaissance (a time of sea
  voyage), but since has often been overlooked. It
  is an illness with high morbidity and mortality
  that is easily treated when properly diagnosed.
  We present the case of a 4 year old male with
  significant lower extremity pain who ceased to
  walk for nearly one year. He presented to us with
  bleeding and friable gingiva, muscle wasting,
  prominence of wrists, knees, and ankles,
  persistent lower limb pain, and significant
  changes in mood. After extensive work up at an
  outside hospital, our history revealed a severely
  restricted diet as a consequence of his behavior,
  and this information coupled with his physical
  exam led to a diagnosis of Scurvy. Limb pain is
  a common pediatric complaint for which Scurvy
  should remain on the differential. A detailed
  history and comprehensive physical exam can limit
  excessive radiographic and invasive
  investigation, as well as decrease the severity
  and duration of disease.

3
Historical Perspective

• 50-80 of 15 -18th century sea voyagers died of a
  disease now known as scurvy.
• James Lind became famous for his 1753 Treatise of
  the Scurvy.
• He recommended lemon juice in the prevention and
  cure of scurvy.

4
Descriptions of Scurvy

• Change of colour in the facepale and bloated
  with a greenish cast
• Lazy and inactive disposition, portend a future
  scurvy
• Stiffness and feebleness of their knees upon
  using exercise
• Gums soon become itchy, swell, and are apt to
  bleed upon the gentlest friction
• Breath is often offensive and gums appear of
  unusual livid redness, are soft and spongy, and
  become extremely putrid and fungous the
  pathognomonic sign of the disease
• Subject not only to bleeding of gums, but prone
  to fall into hemorrhages from other parts of the
  body
• Skin covered with several reddish, bluish, or
  rather black and livid spots with extravasation
  under it, as it were from a bruise

5
Epidemiology

• Scurvy still affects many often overlooked.
• Highest risk
• homeless, alcoholic, anorexic (aversions
  limited diets), mentally ill, poor elderly,
  socially isolated, patients with cancer, AIDS,
  on TPN with no Vit C supplement, malabsorption,
  renal dialysis (Vit C not protein bound)7
• Infants 6 -24 months old are most susceptible,
  especially if diet is solely pasteurized milk
• (heat degrades most Vit C).9

6
Key Functions of Vitamin C

• Water-soluble essential vitamin
• Active transport absorption in ileum
• Acts as a metabolic antioxidant
• Increases absorption of nonheme iron
• Involved in catecholamine biosynthesis (DOPA ?
  NE)
• Necessary for wound healing through hydroxylation
  of proline to precollagen and assembly of mature
  collagen triple helices

7
Initial Symptoms May Be Nonspecific

• Malaise
• Weakness
• Myalgia
• Diarrhea
• Depression
• Coiled corkscrew body hair
• Blood vessel fragility
• Gingivitis

8
Clinical Features of SCURVY

• Severe lower limb pain (subperiosteal bleeding),
  lower limb edema, arthralgia esp. the knee, ankle
  and wrist
• Bone changes decreased osteoblastic activity,
  defect in osteoid matrix formation and cartilage
  resorption (prone to fracture at the growth
  plate)
• Bleeding anemia (decreased iron absorption),
  purpuric rash, petechia, ecchymosis from vessel
  wall damage to poor collagen formation
• Skin changes keratin abnormalities, corkscrew
  body hair or alopecia
• Mood changes decreased ability to convert Dopa ?
  NE, resulting in potential depression or
  irritable mood

9
Patient Case Presentation

• Pt was 4 yr 4 m/o Hispanic male with PMH only
  significant for speech delay until 11 months
  prior to our admission (PTA) when gait changed
  over 2 weeks from legs turned out, to reluctant
  to walk fast or jump, to preferring to crawl.
• Evaluated by PCP leg X-rays negative. Rapid
  progression over 1 wk to pain and no walking, so
  seen again and ESR elevated to 85.
• Pedi Ortho evaluation same day. Bone scan
  negative. By next day, ESR 46 and pt walking.

10
Timeline of Illness Diagnostic Tests

• One week later (10 months PTA), pt crabby with
  pain, crawling using forearms, not walking. Had 2
  wk outside childrens hospital admission for
  Ortho Heme-Onc eval. Arms hurt. Pt curled in a
  ball.
• MRI fluid around joints and femur with
  increased signal of left femur distal metaphysis
• BM biopsy lymphocytosis, otherwise normal
• Lortab did not help with pain.
• Pt improved, discharged, but worse in 1 wk, so
  admitted to outside specialty childrens hospital.

11
Multiple Specialists Involved

• Neurology brain MRI normal.
• EMG/NCS myopathic changes with preserved nerve
  conduction velocities
• Muscle biopsy Type 1 fiber predominance, Type 2
  atrophy. No denervation, inflammatory or
  dystrophic myopathy. Increased lipid. EM - normal
  mitochondria
• Metabolic/Genetics acylcarnitine profile, Beta
  glycoside for Gaucher disease, karyotype,
  comparative genome hybridization all WNL
• Rhematology autoimmune Ab all normal
• ID EBV IgG elevated with normal EBV IgM
• Endocrinology thyroid studies, cortisol, and
  Vit D within normal range

12
More Specialists Involved

• Oncology MRI concerning for leukemia or
  malignant process. CBC within normal limits. CT
  of chest/abdomen/pelvis negative except for mild
  splenomegaly. BM biopsy negative for malignancy.
  
• Hematology anemia
• 10 mo PTA - WBC 5.0 H/H 9/25 Plt 260 RDW
  14.9 MCV 73.2 ESR 56
• 8 mo PTA - WBC 6.5 H/H 10.6/31 Plt 209 RDW
  13.7 MCV 70.6 ESR 10
• Rx for iron was given, but not taken initially
• Neurology multiple lab studies all within
  normal limits. chronic pain, not ambulating
  pain meds added Toradol, Morphine, Tylenol 3.

13
Brief Ambulation at Home

• Pt discharged home no diagnosis
• One months later, less pain pain meds prn.
  Standing, wide-based gait. Less wasted.
• 7 months PTA began PT/OT/ST
• Improving slowly until 4 months PTA, again severe
  leg pain progressing to refusal to bear weight.

14
Another Subspecialty Childrens Hospital
Evaluation

• Four months PTA
• Repeat MRI
• Fairly symmetric foci of abnormal metaphyseal
  signal involving distal femur, proximal and
  distal tibia, and sacrum
• Gadolinium enhancement of involved bone marrow
  with ring enhancing lesion in proximal left
  metaphysis and distal femur periosteal reaction
• 3-phase bone scan abnormal, consistent with
  left sacroiliac joint inflammation

15
More Radiologic Invasive Studies

• 2 mo PTA, pt fitted with orthotics for pes
  planus.
• One month PTA, repeat studies included
• Bone Scan negative
• MRI of bilateral legs Multifocal marrow signal
  abnormality bilaterally pattern suggestive of
  leukemia/lymphoma or histiocytosis.
• CT of lower extremities Subtle edema adjacent
  to proximal tibia metaphysis. Bony structures
  otherwise unremarkable.
• CT needle biopsy of left hip noncontributory
• Returned home with little improvement

16
Summary

• In all, patient had
• Four MRI scans spine and lower extremities
• Four CT scans chest, abdomen, pelvis X 2,
  repeat pelvis, and hip/femur
• Three bone scans
• Two biopsies for bone and marrow aspirate as well
  as a muscle biopsy
• One skeletal survey
• Countless lab tests of nearly every organ system
• and still no definitive diagnosis.

17
Approaching Final Diagnosis

• Latest studies suggested pts diagnosis was
  recurrent multifocal osteomyelitis, so PCP
  referred pt for admission to UTHSCSA pediatric
  childrens hospital for IV antibiotics.
• Chronic symptomatology with distinct periods when
  pt had escalation of severe leg pain. Mostly
  non-ambulatory with chronic muscle wasting.
  Little improvement with outpatient
  rehabilitation.
• Home medications Tylenol 3 q 4 hrs, Toradol 1/2
  tablet q day (prn) X 2 months, Roxinol, and iron
  BID
• ROS Additional findings - irritable mood 6
  weeks of bleeding gums mushy stools. No history
  of skin rash.

18
Birth History

• TSVD with good prenatal care, Apgars 8/8 and
  birth weight 8lbs 12 oz
• 20 week US showed 2-vessel cord, noted at birth,
  but no kidney problems found
• Pt went home with parents from hospital no
  complications.

19
Further History

• No hospitalizations or surgeries except related
  to current illness
• FMHx 6 y/o sister with schizencephaly, mild
  left hemiplegia, but appropriate school grade for
  age. 11 month old sister - no medical problems
• Social Lives with Mom, Dad, 2 sisters, outside
  cats, no smoke exposure

20
History is Important Diet

• Diet Long history of VERY PICKY EATER.
• No milk, juices. Rare fruits, vegetables. No
  multivitamins.
• Transition to table food at 10-11 month
• Transition to whole milk at 1 y/o. Used only one
  specific bottle and nipple. When pt 2 yrs old,
  nipple wore out. Pt refused milk from any other
  container or nipple gagged on milk from cup.
• No milk since 2 1/2 yrs old.

21
History is Important Diet

• Dietary intake on admission waffles with syrup,
  sausage patty, bean tacos, pizza (cheese or
  pepperoni), popcorn brown sodas, tea.
• Pt demanded certain foods not touch each other,
  and he refused to try certain foods based on
  texture or color.
• No multivitamin intake. No supplemental nutrition
  (oral, NG or IV) during prior hospitalizations.

22
History is Important Behavior

• Patient was extremely irritable 7 months PTA.
  Mother described fits of screaming and onset of
  tantrums.
• Known speech delay with only approximately 50
  intelligibility, a few phrases, mostly repetitive
  language
• By age 3, had behavior of lining up his Care
  Bears by height and carrying books stacked only
  in a particular order.
• Great difficulty with transitions. (Sisters
  birth coincided with onset of leg pain
  complaints.)
• Sensory integration difficulties regarding
  dietary habits.
• Not yet toilet trained.

23
History is Important Development

• Patient started walking at 14 months of age.
• 10 mo PTA, pt would often curl up into a ball
  crying that his legs hurt and wanted to be
  carried.
• Pt refused to get off sofa bear weight, would
  scream and cry, began crawling to get around.
• 8 mo PTA, patient resumed walking, but with
  wide-based gait and Gower sign to stand.
• 5 mo PTA, pt had regressed to crawling and
  screaming in pain once again.

24
Pertinent Physical Exam Findings

• Alert, fearful, crying with exam
• Periodontal erythema, swelling. Friable
  gingivae. Hard palate 1X1 cm mass anterior left
  maxillary areas. Dried blood very chapped, split
  lips.

25
Pertinent Physical Exam Findings

• Muscle wasting evident
• Chest - faint rachitic rosary
• Marked atrophy of UE LE muscles with 4/5
  strength. No rash, petechiae.
• Keeps knees flexed. Can wiggle toes with no pain
  wont straighten legs.
• Firm flared swelling at wrists, knees, and
  ankles. No erythema, warmth, tenderness, or edema.

26
Differential Diagnosis

• Chronic recurrent multifocal osteomyelitis
• Leukemia, lymphoma, histiocytosis
• Infection great imitators TB, HIV, syphilis
• Metabolic-genetic disorder
• Extensive PTA testing. Most likely was Gaucher
  disease, but definitive testing normal.
• Rickets disease
• PTA tests X-linked rickets still possible.
• Copper deficiency pseudoscurvy11

27
Differential Diagnosis

• Sjogrens vasculitis
• mimics arthralgia, myalgia, purpura, sicca (PTA
  Rheum evaluation negative).
• From detailed HISTORY and PE findings, primary
  diagnostic considerations became malnutrition and
  scurvy.
• Must consider underlying malabsorption as cause,
  if scurvy cystic fibrosis, celiac sprue, Crohn,
  Whipple.

28
Important History

• Nutritional Pt refused to eat any fruits,
  vegetables, juices. No milk, limited dairy.
  Essentially no Vit C in diet. This aspect not
  addressed in any prior evaluation. No dietary
  advice or supplements given.
• Behavioral Sensory integration problems
  regarding certain oral textures leading to
  limited diet. Speech delay with repetitive
  quality. Irritable mood at onset of myalgias.
• Dental Routine exam 2 mo PTA. No gum changes or
  bleeding, teeth OK. Dentist asked why pt had
  general health decline scheduled 3 mo recheck
  (usual 6 mo).
• Anemia
• Severe lower leg pain and prominent joints
• Bone changes on radiography

29
Imaging

• Radiographs show diffuse osteopenia
• Scurvy Line or White line of Frankel dense band
  at the growing metaphyseal end involving the
  provisional zone of calcification
• Wimbergers ring small epiphysis surrounded by
  a sharp scleroticrim
• Pelkans spur metaphyseal beaks projecting at
  right angles to shaft axis

30
Laboratory Studies

• Rickets Vit D, Phos, Alk Phos WNL
• Copper 211 (ref 90-190). WNL
• CF Sweat test - negative
• Celiac disease normal profile
• Gaucher/Pompe prior definitive testing WNL
• Stool studies all neg for reducing substances
• PPD, RPR and HIV negative

31
Ascorbic Acid

• Pts Vit C level 0.1 mg/dL (ref level 0.4 -
  2.0 mg/dL)
• Plasma Vitamin C status considered depleted
  between 0.2 - 0.5 mg/dL4
• Below 0.2 mg/dL, deficient
• A low level of plasma vitamin C is specific to
  scurvy 8
• One may have scurvy without a low Vit C level
  however, significant depletion coupled with PE
  findings is diagnostic.

32
We Need Vitamin C

• We cannot make itVitamin C is an essential
  vitamin.
• We store it poorly With no intake, Vit C becomes
  depleted in 40 days. 7
• Symptoms of scurvy begin to develop after 60-90
  days of no Vitamin C.
• Skin lesions can appear in 130 days.
• Dental abnormalities appear in 6 months time.
• Prolonged deficiency of Vitamin C may cause death.

33
Dietary History Is Crucial

• This case clearly shows that a detailed dietary
  history could have potentially saved this 4 y/o
  child from undergoing much radiation, painful
  procedures, emotional and developmental
  detriment, nearly a years inability to walk, and
  major medical expenses.
• Dietary history is very important, since many
  people have consequences of improper nutrition.
  Scurvy is an easily treated disease, once
  diagnosed.
• Untreated, scurvy can cause sudden death from
  fatal infections due to poor wound healing or
  impaired catecholamine biosynthesis and
  secretion.
• Severe bleeding, poor immune function, seizures,
  cardiac abnormality, and cancer due to decreased
  antioxidants are all repercussions of deficient
  dietary Vitamin C.

34
Treatment

• Based on medical literature, our patient was
  treated with Vitamin C 125 mg IV qid7,8
• Within 48 hours of initiating therapy, pt showed
  gingival healing with decreased gum friability.
• Pts mood rapidly improved with decreased
  irritability, less apprehension on exam, and he
  was once again pleasant with family.
• Within days, pt straightened legs with little
  pain.
• Pt underwent extensive nutritional management,
  psychological and developmental evaluations, and
  comprehensive rehabilitation services.

35
Nutritional Rehabilitation

• Dietary evaluation calorie count showed pts
  intake at best met only 56 of minimum daily
  required calories for age.
• Ongoing management through dietitian
• Child Life Speech TX helped pt in both tactile
  and oral play with different textures of food.
• Vit C supplement was one part of dietary and
  feeding intervention.
• Meals/dietary variety encouraged. NG tube
  tolerated well. Bolus continuous night feeds
  begun with monitoring for refeeding syndrome.

36
Nutritional Rehabilitation

• Behavior and development issues, aversions,
  delays, and possible OCD/PDD behaviors were
  addressed through psychiatry, developmental
  pediatrics and Child Life services.
• Pt was transferred to the rehab service for PT,
  OT ST. Improved after 3 weeks intensive therapy.
  Could walk independently using orthotics.
• Discharged with dietary regimen, no tea, sodas.
  NG night feeds, multivitamin, iron. No pain meds.
• After 2 mo, pt achieved good caloric intake
  broader array of foods, milk, juice. NG feeds
  stopped. In comprehensive rehab school PCI.

37
Behavioral Assessment

• Concern for behaviors which led to patients
  Vitamin C deficiency were addressed in outpatient
  setting with a behavioral specialist.
• Patient is receiving ongoing care with
  PT/OT/Speech Therapy and PPCD school program.
• He is on the PDD spectrum. Clinically, he
  appears autistic, but without developmental
  endorsements, it is not possible to confirm this
  diagnosis and further testing is needed.
• By addressing the behaviors which impeeded an
  appropriate diet, our patient has tolerated a
  better variety with sufficient nutritional intake.

38
Discussion

• Our approach to this case was to take a step
  back, assess what studies had been done PTA, and
  consider what information was lacking.
• Based on physical exam findings a detailed
  dietary history, combined with a broad
  differential, we were able to make the definitive
  diagnosis of scurvy within two days.
• We hypothesize that the patients intermittently
  improved condition during the PTA time period may
  have hinged on infectious disease hits to his
  already minimal Vitamin C.
• The immune system requires increased utilization
  of Vitamin C to fight infections, such that when
  the pt needed to fight infection, he may have
  used up any Vit C reserve.
• A minor illness often preceded the pts escalated
  intensity of extremity pain and subsequent
  refusal to ambulate.

39
Discussion

• Are children on the autistic spectrum at
  increased risk for Vit C deficiency?
• An OVID literature search yielded no research
  studies on Autism/PDD and malnutrition or vitamin
  deficiencies.
• There are reference cases that report patients
  with Autism and developmental delay having a
  similar presentation and the diagnosis of
  scurvy.10
• Vitamin deficiency in children with behavior and
  development problems may be more common than is
  realized.

40
Look Outside the Box

• Few physicians have first-hand experience with
  scurvy, but that does not mean it is not around
  us.
• To diagnose a disease, you must know about it,
  and then you must look for it.

41
Final Thoughts

• "Let your food be your medicine, and your
  medicine be your food." Hippocrates.

42
References

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