# Clinical Cases: Nutrition and Dietetics

## Case 1: Vitamin B12 Deficiency in Vegan Patient

### Patient Presentation
**Demographics:** 34-year-old female graphic designer

**Chief Complaint:** "I've been feeling exhausted, my hands and feet tingle, and I keep forgetting things."

**History of Present Illness:**
Ms. Patel adopted a strict vegan diet four years ago for ethical and environmental reasons. She has been conscientious about her diet, consuming a variety of whole grains, legumes, fruits, and vegetables. However, she has never taken a B12 supplement, stating she believed she could obtain adequate nutrition from plant sources alone. She was not aware that vitamin B12 is essentially absent from unfortified plant foods.

Over the past six months, she has developed progressive fatigue that limits her ability to work full days. She describes bilateral paresthesias in her hands and feet ("pins and needles"), which initially occurred intermittently but are now constant. She reports increasing difficulty with concentration and short-term memory, often forgetting conversations and misplacing items. Her partner has noticed she has become more irritable and emotionally labile.

She also describes a sore, smooth tongue that makes eating spicy foods painful, intermittent diarrhea, and a feeling of unsteadiness when walking in the dark. She has noticed shortness of breath with climbing two flights of stairs, which she attributed to being "out of shape." She denies heavy menstrual bleeding or other sources of blood loss.

**Past Medical History:**
- No significant medical history
- No surgeries (specifically no gastric surgery)
- No history of autoimmune disease

**Medications:**
- No prescription medications
- Occasional iron supplement (self-directed, not consistent)
- No B12 supplementation
- No fortified foods regularly consumed

**Social History:**
- Strict vegan for 4 years (no eggs, dairy, or any animal products)
- Graphic designer; works from home
- Non-smoker; social alcohol (wine, 1-2 glasses/week)
- Avid yoga practitioner
- No recreational drug use; no nitrous oxide exposure

**Family History:**
- Mother: Pernicious anemia (diagnosed at age 55)
- Father: Type 2 diabetes
- Non-contributory otherwise

### Physical Examination
- **Vital Signs:** BP 110/68 mmHg, HR 102 bpm, RR 18, Temp 98.8°F, SpO2 97%, BMI 21.4 kg/m²
- **General:** Pale-appearing female; appears fatigued
- **HEENT:** Pale conjunctivae; icteric sclerae (mild); glossitis — smooth, beefy-red tongue with loss of papillae; angular cheilitis
- **Cardiovascular:** Tachycardic; systolic flow murmur grade II/VI at left sternal border (anemia-related)
- **Respiratory:** Clear; mild tachypnea
- **Abdomen:** Soft, non-tender; no hepatosplenomegaly
- **Neurological:** Decreased vibratory sensation bilateral ankles and toes (128 Hz tuning fork); decreased proprioception bilateral great toes; positive Romberg sign; bilateral Babinski signs (extensor plantar responses); diminished ankle reflexes; gait slightly wide-based
- **Extremities:** No edema; pallor of nail beds
- **Psychiatric:** Affect mildly flat; MMSE 27/30 (lost points on recall and attention)

### Workup and Results

**Laboratory Studies:**
| Test | Result | Reference Range |
|------|--------|-----------------|
| Hemoglobin | 8.4 g/dL | 12-16 g/dL |
| Hematocrit | 25.8% | 36-46% |
| MCV | 118 fL | 80-100 fL |
| MCH | 38.2 pg | 27-33 pg |
| RDW | 18.4% | 11.5-14.5% |
| WBC | 3.8 x10³/µL | 4.5-11.0 x10³/µL |
| Platelets | 128 x10³/µL | 150-400 x10³/µL |
| Reticulocyte Count | 0.8% | 0.5-2.5% |
| Vitamin B12 | 68 pg/mL | 200-900 pg/mL |
| Methylmalonic Acid | 2,840 nmol/L | 73-271 nmol/L |
| Homocysteine | 38.4 µmol/L | < 15 µmol/L |
| Folate | 18.2 ng/mL | > 3.0 ng/mL |
| Iron | 82 µg/dL | 37-145 µg/dL |
| Ferritin | 42 ng/mL | 12-150 ng/mL |
| LDH | 1,240 U/L | 140-280 U/L |
| Indirect Bilirubin | 2.1 mg/dL | 0.1-1.0 mg/dL |
| Haptoglobin | 12 mg/dL | 30-200 mg/dL |
| Intrinsic Factor Antibodies | Negative | Negative |
| Anti-Parietal Cell Antibodies | Negative | Negative |

**Imaging/Additional Studies:**
- Peripheral blood smear: Macroovalocytes, hypersegmented neutrophils (> 5 lobes), anisocytosis, poikilocytosis
- MRI Brain and Spine: T2 hyperintensity in posterior columns of cervical and thoracic spinal cord (subacute combined degeneration); no intracranial abnormalities
- Nerve conduction studies: Axonal sensorimotor polyneuropathy predominantly affecting lower extremities

### Clinical Image

![Medical illustration showing the neurological manifestations of B12 deficiency including subacute combined degeneration of the spinal cord with demyelination of the dorsal columns and corticospinal tracts](case_01_image.jpg)

*Cross-sectional diagram of the spinal cord demonstrating subacute combined degeneration from vitamin B12 deficiency, showing demyelination of the posterior columns (proprioception, vibration) and lateral corticospinal tracts (upper motor neuron signs), with corresponding clinical manifestations. Source: Educational illustration.*

### Diagnosis
**Severe Vitamin B12 Deficiency with Megaloblastic Anemia and Subacute Combined Degeneration of the Spinal Cord (ICD-10: D51.0, E53.8, G32.0)**

**Key Diagnostic Criteria:**
- Serum B12 critically low (68 pg/mL; < 200 diagnostic)
- Markedly elevated methylmalonic acid and homocysteine (functional B12 deficiency biomarkers)
- Macrocytic anemia (MCV 118) with pancytopenia and classic smear findings (hypersegmented neutrophils)
- MRI evidence of subacute combined degeneration (posterior column T2 signal)
- Neurological examination consistent with dorsal column dysfunction (vibration, proprioception loss, Romberg positive) and corticospinal tract involvement (Babinski signs)
- Etiology: dietary deficiency (strict vegan without supplementation)

### Treatment Plan
1. **Urgent B12 Replacement:** Intramuscular cyanocobalamin 1000 mcg daily for 7 days, then weekly for 4 weeks, then monthly indefinitely; IM route preferred over oral given neurological involvement and severity
2. **Potassium Monitoring:** Check potassium at 48 hours — rapid reticulocytosis can cause hypokalemia as potassium shifts into newly forming red cells
3. **Reticulocyte Crisis Monitoring:** Expect reticulocyte count peak at days 5-7 (confirms diagnosis and response to treatment)
4. **Neurological Recovery Monitoring:** Peripheral neuropathy may improve over months; posterior column lesions on MRI may partially or fully resolve; early treatment initiation is critical — neurological damage present > 6 months may be irreversible
5. **Folate Supplementation:** Add folic acid 1 mg daily (folate can mask hematological signs of B12 deficiency but will NOT prevent neurological damage — always replace B12 first)
6. **Dietary Counseling:** Vegan diet can be nutritionally complete with proper supplementation; lifelong B12 supplementation mandatory (minimum 250 mcg/day oral or 2500 mcg/week); recommend B12-fortified nutritional yeast, plant milks, and cereals as dietary sources; dietitian referral for comprehensive vegan nutrition planning
7. **Screen for Other Deficiencies:** Check vitamin D, omega-3 index, zinc, iodine — nutrients commonly insufficient in unsupplemented vegan diets
8. **Family History Note:** Mother's pernicious anemia is autoimmune and distinct from dietary deficiency, but patient should be monitored for future development of autoimmune gastritis (intrinsic factor and parietal cell antibodies currently negative)
9. **Follow-up:** CBC at 1 week (reticulocyte response), 1 month (Hgb improvement), 3 months (normalization); B12 and MMA at 3 months; repeat MRI spine at 6 months; neurological exam at each visit

### Key Learning Points
- Vitamin B12 is exclusively produced by microorganisms and is found naturally only in animal-derived foods; strict vegans absolutely require supplementation or fortified foods — hepatic B12 stores can sustain a person for 3-5 years before deficiency manifests
- Methylmalonic acid (MMA) is the most specific biomarker for B12 deficiency and is elevated even when serum B12 is in the low-normal range; homocysteine is elevated in both B12 and folate deficiency and thus is less specific
- Subacute combined degeneration is a neurological emergency — the degree of neurological recovery is directly related to the duration of symptoms before treatment; neurological damage that has been present > 12 months is often irreversible
- Folate supplementation alone in a B12-deficient patient can correct the anemia (normalizing MCV and blood counts) while allowing neurological damage to progress silently — this is why it is critical to always check B12 before attributing macrocytic anemia to folate deficiency
- The peripheral blood smear finding of hypersegmented neutrophils (≥ 5 lobes in ≥ 5% of neutrophils, or any neutrophil with ≥ 6 lobes) is highly specific for megaloblastic anemia and should trigger immediate B12 and folate measurement

---

## Case 2: Refeeding Syndrome

### Patient Presentation
**Demographics:** 22-year-old female college student

**Chief Complaint:** Brought to emergency department by roommate for "confusion and not eating for weeks."

**History of Present Illness:**
Ms. Garcia is a 22-year-old college senior brought to the ED by her roommate, who reports that the patient has been eating "almost nothing" for the past three weeks and has become increasingly confused and lethargic over the past 24 hours. The roommate states that Ms. Garcia has been under extreme academic pressure and has been restricting food intake, initially skipping meals and progressing to consuming only water, black coffee, and occasional crackers.

The patient has a known history of anorexia nervosa, diagnosed at age 16, with multiple treatment episodes. She was weight-restored and in partial remission for the past 18 months but relapsed at the start of the current semester. She has lost approximately 20 pounds over the past 6 weeks, declining from 115 pounds to 95 pounds (BMI declining from 19.7 to 16.3).

Upon ED presentation, she is oriented to person and place but not to time. She is hypotensive and bradycardic. The ED team recognizes her as severely malnourished and begins intravenous dextrose-containing fluids and plans to initiate enteral nutrition. This case illustrates the critical importance of recognizing refeeding risk before initiating nutritional rehabilitation.

**Past Medical History:**
- Anorexia nervosa, restricting type (diagnosed age 16; two prior inpatient admissions)
- Secondary amenorrhea (intermittent)
- Osteopenia (diagnosed age 19)
- Major depressive disorder

**Medications:**
- Fluoxetine 40 mg daily (has not been taking for 2 weeks)
- Multivitamin (has not been taking)

**Social History:**
- College senior; pre-law track
- Lives in campus housing with roommate
- Non-smoker; no alcohol or drug use
- High academic achiever; describes perfectionist traits
- Estranged from parents; limited support system

**Family History:**
- Mother: Generalized anxiety disorder
- Maternal aunt: Anorexia nervosa

### Physical Examination
- **Vital Signs:** BP 82/54 mmHg (supine), HR 48 bpm, RR 12, Temp 96.8°F, SpO2 96%, BMI 16.3 kg/m²
- **General:** Cachectic, lethargic young female; temporal wasting; prominent bony landmarks
- **HEENT:** Sunken eyes; dry, cracked lips; lanugo hair on face; parotid gland enlargement bilateral (mild); dental enamel erosion not present (restricting subtype)
- **Cardiovascular:** Bradycardic; regular rhythm; distant heart sounds; no murmurs; weak peripheral pulses; capillary refill 4 seconds
- **Respiratory:** Clear but diminished breath sounds at bases; shallow respirations
- **Abdomen:** Scaphoid; hyperactive bowel sounds; no tenderness
- **Extremities:** Marked muscle wasting; cold, mottled, acrocyanotic hands and feet; trace pedal edema; no deep vein thrombosis signs
- **Skin:** Dry, lanugo hair on arms and back; bruising on shins; poor turgor
- **Neurological:** Oriented x2; lethargic but arousable; diminished deep tendon reflexes globally; Chvostek sign positive (facial twitching with tapping of facial nerve); Trousseau sign positive (carpopedal spasm with BP cuff inflation)

### Workup and Results

**Laboratory Studies (on admission, BEFORE refeeding):**
| Test | Result | Reference Range |
|------|--------|-----------------|
| Phosphorus | 1.8 mg/dL | 2.5-4.5 mg/dL |
| Magnesium | 1.2 mg/dL | 1.7-2.2 mg/dL |
| Potassium | 2.9 mEq/L | 3.5-5.0 mEq/L |
| Sodium | 131 mEq/L | 136-145 mEq/L |
| Glucose | 52 mg/dL | 70-99 mg/dL |
| Albumin | 2.4 g/dL | 3.5-5.0 g/dL |
| Prealbumin | 8 mg/dL | 20-40 mg/dL |
| BUN | 28 mg/dL | 7-20 mg/dL |
| Creatinine | 0.9 mg/dL | 0.5-1.1 mg/dL |
| ALT | 68 U/L | 7-56 U/L |
| AST | 82 U/L | 10-40 U/L |
| Hemoglobin | 10.8 g/dL | 12-16 g/dL |
| WBC | 2.8 x10³/µL | 4.5-11.0 x10³/µL |
| Thiamine | Low (below assay) | 70-180 nmol/L |
| Zinc | 42 µg/dL | 60-120 µg/dL |

**After initiation of IV dextrose (Day 2 — demonstrating refeeding shift):**
| Test | Result | Reference Range |
|------|--------|-----------------|
| Phosphorus | 0.8 mg/dL | 2.5-4.5 mg/dL |
| Potassium | 2.4 mEq/L | 3.5-5.0 mEq/L |
| Magnesium | 0.9 mg/dL | 1.7-2.2 mg/dL |
| Glucose | 184 mg/dL | 70-99 mg/dL |

**Imaging/Additional Studies:**
- ECG (admission): Sinus bradycardia 48 bpm; prolonged QTc 512 ms; flattened T-waves; U-waves present
- ECG (Day 2, post-refeeding): New ST-depression V4-V6; QTc 548 ms
- Echocardiogram: Reduced LV mass; EF 45% (mildly reduced); small pericardial effusion
- Chest X-ray: Small bilateral pleural effusions; no pulmonary edema

### Clinical Image

![Medical diagram showing the pathophysiology of refeeding syndrome including the shift from fat metabolism to carbohydrate metabolism, insulin surge, and intracellular electrolyte shifts causing dangerous hypophosphatemia, hypokalemia, and hypomagnesemia](case_02_image.jpg)

*Pathophysiology of refeeding syndrome illustrating the metabolic shift: during starvation, the body adapts to fat and ketone metabolism with depleted intracellular electrolyte stores. Upon carbohydrate reintroduction, insulin surges drive glucose, phosphorus, potassium, and magnesium intracellularly, causing precipitous serum drops that can lead to cardiac arrhythmias, respiratory failure, seizures, and death. Source: Educational illustration.*

### Diagnosis
**Refeeding Syndrome (ICD-10: E43, E83.39, E87.6)**

**Key Diagnostic Criteria:**
- Severely malnourished patient (BMI 16.3, minimal intake for 3+ weeks)
- Precipitous drop in phosphorus from 1.8 to 0.8 mg/dL after carbohydrate reintroduction (hallmark of refeeding syndrome)
- Concurrent worsening of potassium and magnesium
- ECG deterioration (prolonging QTc, new ST changes)
- Clinical deterioration after initiation of IV dextrose
- NICE criteria for high refeeding risk met: BMI < 18.5, unintentional weight loss > 15%, negligible intake > 10 days, and low baseline electrolytes

### Treatment Plan
1. **STOP Dextrose-Containing Fluids Immediately:** The IV dextrose triggered the refeeding cascade; switch to normal saline without dextrose
2. **Phosphorus Replacement (Priority):** IV sodium phosphate or potassium phosphate 30-45 mmol over 6 hours with cardiac monitoring; recheck phosphorus every 6 hours; maintain > 2.0 mg/dL
3. **Potassium Replacement:** IV potassium chloride 40 mEq over 4 hours (central line preferred given concentration); continuous cardiac monitoring; target > 3.5 mEq/L; do NOT replace potassium in dextrose-containing solutions
4. **Magnesium Replacement:** IV magnesium sulfate 2 g over 2 hours; magnesium must be repleted before potassium will correct (magnesium depletion causes renal potassium wasting)
5. **Thiamine Replacement (BEFORE any carbohydrate):** IV thiamine 200-300 mg daily for 3 days, then oral 100 mg daily; thiamine MUST precede carbohydrate administration to prevent Wernicke encephalopathy — the dextrose given without thiamine was a critical error
6. **Cautious Refeeding Protocol:** Start at 10 kcal/kg/day (approximately 430 kcal/day); advance by 5 kcal/kg/day every 24-48 hours if electrolytes remain stable; goal of 30-40 kcal/kg/day by day 7-10; use low-carbohydrate, moderate-fat formulations initially
7. **Continuous Cardiac Monitoring:** ICU admission; telemetry for QTc monitoring (risk of torsades de pointes); daily ECGs
8. **Electrolyte Monitoring:** BMP every 6-8 hours for first 72 hours; daily thereafter for 5-7 days; phosphorus, magnesium, and potassium checked together always
9. **Multidisciplinary Team:** Psychiatry, nutrition, internal medicine, cardiology co-management; transition to eating disorder unit when medically stable
10. **Long-term Plan:** Residential eating disorder treatment program referral; family therapy; relapse prevention planning

### Key Learning Points
- Refeeding syndrome is a potentially lethal metabolic complication characterized by severe hypophosphatemia, hypokalemia, and hypomagnesemia occurring when carbohydrates are reintroduced to a severely malnourished patient
- Hypophosphatemia is the hallmark of refeeding syndrome — phosphorus is consumed by ATP synthesis and 2,3-DPG production during the sudden shift from fat to carbohydrate metabolism; levels below 1.0 mg/dL can cause respiratory failure, cardiac arrest, and death
- Thiamine must ALWAYS be administered before any carbohydrate in malnourished patients — glucose metabolism consumes thiamine, and administering glucose to a thiamine-depleted patient can precipitate Wernicke encephalopathy
- The NICE guidelines identify five risk criteria for refeeding syndrome: BMI < 18.5, unintentional weight loss > 10% in 3-6 months, little/no nutritional intake > 5 days, low baseline phosphorus/potassium/magnesium, and history of alcohol misuse or certain medications (insulin, chemotherapy, diuretics)
- The initial refeeding rate should be 10 kcal/kg/day for high-risk patients (5 kcal/kg/day for extreme risk, BMI < 14), with slow advancement — "start low and go slow" is the cardinal rule of nutritional rehabilitation

---

## Case 3: Celiac Disease with Nutritional Deficiencies

### Patient Presentation
**Demographics:** 38-year-old female elementary school teacher

**Chief Complaint:** "I've had diarrhea and bloating for years, and now I'm having a rash and my bones ache."

**History of Present Illness:**
Mrs. O'Brien presents with a constellation of symptoms she has experienced to varying degrees for the past seven years. She reports chronic intermittent diarrhea (3-5 loose, bulky, foul-smelling, pale stools daily), abdominal bloating and cramping that worsens after meals, and progressive fatigue. She was previously diagnosed with irritable bowel syndrome and has been on a low-FODMAP diet with partial but incomplete symptom relief.

Over the past 12 months, her symptoms have intensified. She has developed an intensely pruritic, blistering rash on her elbows, knees, and buttocks that she initially attributed to eczema. She reports diffuse bone and joint pain, particularly in her hips and lower back. She has had two episodes of tingling and cramping in her hands and feet. She has experienced difficulty conceiving (18 months of unprotected intercourse without pregnancy). Her weight has decreased by 12 pounds despite maintaining her usual caloric intake.

She reports a history of iron deficiency anemia that was "hard to correct" with oral iron supplements. She was noted to have "low vitamin D" two years ago but did not follow up. She has a maternal cousin who was diagnosed with celiac disease in childhood.

**Past Medical History:**
- "Irritable bowel syndrome" (diagnosed age 31 — likely misdiagnosis)
- Iron deficiency anemia (recurrent, refractory to oral iron)
- Vitamin D deficiency (identified but not adequately treated)
- Infertility (18 months)
- Childhood history of short stature (5th percentile until age 14)

**Medications:**
- Dicyclomine 20 mg as needed for cramping
- Ferrous sulfate 325 mg daily (inconsistent use due to GI side effects)
- Loperamide as needed

**Social History:**
- Elementary school teacher
- Married; actively trying to conceive
- Non-smoker; rare alcohol
- Diet: Standard American diet with bread, pasta, cereals as staples; attempted low-FODMAP with partial relief (notably, low-FODMAP reduces but does not eliminate wheat)

**Family History:**
- Maternal cousin: Celiac disease (diagnosed in childhood)
- Mother: Hypothyroidism, osteoporosis
- Father: Type 1 diabetes
- Brother: Healthy

### Physical Examination
- **Vital Signs:** BP 108/66 mmHg, HR 92 bpm, RR 16, Temp 98.6°F, BMI 19.8 kg/m²
- **General:** Thin female appearing fatigued; pale
- **HEENT:** Pale conjunctivae; angular cheilitis; dental enamel defects (horizontal grooves and pitting on permanent teeth); two aphthous ulcers on buccal mucosa
- **Cardiovascular:** Tachycardic; soft systolic flow murmur (anemia-related)
- **Respiratory:** Clear
- **Abdomen:** Distended; diffuse tenderness without guarding; hyperactive bowel sounds; no organomegaly
- **Skin:** Grouped, erythematous, vesiculopapular lesions symmetrically distributed on extensor surfaces of elbows bilaterally, knees, and buttocks; many excoriated; herpetiform pattern
- **Musculoskeletal:** Tenderness over bilateral iliac crests and lower thoracic spine with percussion; no deformities
- **Neurological:** Intact; mild decreased vibratory sense bilateral feet

### Workup and Results

**Laboratory Studies:**
| Test | Result | Reference Range |
|------|--------|-----------------|
| tTG-IgA | 128 U/mL | < 4 U/mL |
| Endomysial Antibody (EMA) | Positive (1:160) | Negative |
| Total IgA | 245 mg/dL | 70-400 mg/dL |
| Deamidated Gliadin Peptide IgG | 96 U/mL | < 20 U/mL |
| Hemoglobin | 9.6 g/dL | 12-16 g/dL |
| MCV | 74 fL | 80-100 fL |
| Ferritin | 4 ng/mL | 12-150 ng/mL |
| Iron | 22 µg/dL | 37-145 µg/dL |
| TIBC | 480 µg/dL | 250-370 µg/dL |
| Folate | 3.8 ng/mL | > 3.0 ng/mL |
| Vitamin B12 | 310 pg/mL | 200-900 pg/mL |
| Vitamin D, 25-OH | 11 ng/mL | 30-100 ng/mL |
| Calcium | 7.8 mg/dL | 8.5-10.5 mg/dL |
| Alkaline Phosphatase | 148 U/L | 44-147 U/L |
| PTH | 98 pg/mL | 15-65 pg/mL |
| Zinc | 48 µg/dL | 60-120 µg/dL |
| Copper | 65 µg/dL | 70-175 µg/dL |
| TSH | 6.8 mIU/L | 0.4-4.0 mIU/L |
| TPO Antibodies | 210 IU/mL | < 35 IU/mL |
| Prothrombin Time | 15.2 seconds | 11-13.5 seconds |
| INR | 1.3 | 0.8-1.1 |

**Imaging/Additional Studies:**
- Upper endoscopy with duodenal biopsies: Scalloped duodenal folds; loss of villi on magnification; biopsies show Marsh 3b classification — subtotal villous atrophy with crypt hyperplasia and intraepithelial lymphocytosis (> 40 IELs per 100 enterocytes)
- DEXA scan: Lumbar T-score -2.9; femoral neck T-score -2.4 (osteoporosis)
- Skin biopsy (perilesional): Granular IgA deposits at dermal papillae on direct immunofluorescence (pathognomonic for dermatitis herpetiformis)

### Clinical Image

![Medical illustration showing the intestinal villous atrophy in celiac disease alongside the multiple nutritional deficiencies that result from malabsorption, including iron, calcium, vitamin D, folate, zinc, and fat-soluble vitamins](case_03_image.jpg)

*Celiac disease pathology and nutritional consequences: comparison of normal villous architecture versus Marsh 3b villous atrophy, with a diagram of the specific nutrients malabsorbed at each intestinal segment and resulting clinical manifestations (anemia, osteoporosis, dermatitis herpetiformis, coagulopathy, neuropathy). Source: Educational illustration.*

### Diagnosis
**Celiac Disease (Marsh 3b) with Dermatitis Herpetiformis, Iron Deficiency Anemia, Osteoporosis, Secondary Hyperparathyroidism, and Autoimmune Thyroiditis (ICD-10: K90.0, L13.0, D50.9, M81.0, E21.1, E06.3)**

**Key Diagnostic Criteria:**
- Strongly positive serology: tTG-IgA > 10x upper limit of normal; positive EMA (highly specific)
- Duodenal biopsy confirming Marsh 3b (subtotal villous atrophy) — gold standard for diagnosis
- Dermatitis herpetiformis confirmed by granular IgA deposits on perilesional skin biopsy (pathognomonic; considered "celiac disease of the skin")
- Multiple nutritional deficiency states secondary to proximal small bowel malabsorption
- Associated autoimmune condition (Hashimoto's thyroiditis — common comorbidity)

### Treatment Plan
1. **Strict Lifelong Gluten-Free Diet (GFD):** Complete elimination of wheat, barley, rye, and their derivatives; dietitian referral specializing in celiac disease; education on cross-contamination, hidden gluten sources (sauces, medications, communion wafers), and label reading
2. **Iron Repletion:** IV iron infusion (ferric carboxymaltose 750 mg x 2 doses, 1 week apart) — oral iron poorly absorbed given villous atrophy; target ferritin > 50 ng/mL
3. **Vitamin D and Calcium:** Vitamin D3 50,000 IU weekly for 12 weeks then 2000 IU daily; calcium citrate 600 mg BID (citrate preferred over carbonate due to better absorption in malabsorptive states); recheck at 3 months
4. **Osteoporosis Management:** GFD and nutrient repletion are first-line; reassess bone density with DEXA at 1-2 years after GFD; defer bisphosphonates given desire for pregnancy (teratogenic)
5. **Zinc and Copper Supplementation:** Zinc 30 mg daily; copper 2 mg daily; monitor levels
6. **Coagulopathy:** Vitamin K 10 mg PO daily for 1 week (mildly elevated INR from fat-soluble vitamin malabsorption); recheck PT/INR
7. **Thyroid:** Initiate levothyroxine 50 mcg daily for subclinical hypothyroidism with positive TPO antibodies; recheck TSH in 6-8 weeks
8. **Dermatitis Herpetiformis:** Dapsone 25 mg daily for rapid symptom control while awaiting GFD response (DH may take months to resolve on GFD alone); check G6PD before starting dapsone; monitor CBC and reticulocyte count
9. **Fertility:** Untreated celiac disease is associated with infertility, recurrent miscarriage, and IUGR; GFD adherence and nutritional repletion may restore fertility; refer to reproductive endocrinology if no conception within 6 months of GFD
10. **Follow-up:** tTG-IgA at 6 and 12 months (should decline and normalize with strict GFD); repeat endoscopy at 12-24 months to confirm mucosal healing; screen first-degree relatives

### Key Learning Points
- Celiac disease affects approximately 1% of the population and is underdiagnosed — the average time from symptom onset to diagnosis is 6-10 years; unexplained iron deficiency anemia refractory to oral supplementation is one of the most common presentations in adults
- tTG-IgA is the recommended initial serological test; values > 10x the upper limit of normal with positive EMA are virtually diagnostic and some guidelines (ESPGHAN pediatric criteria) allow diagnosis without biopsy in this setting; total IgA must always be checked to exclude IgA deficiency (which causes false-negative celiac serology)
- Dermatitis herpetiformis is pathognomonic for celiac disease — it is caused by IgA-epidermal transglutaminase (eTG) antibody deposition in the skin; approximately 15-25% of celiac patients develop DH, and nearly all DH patients have intestinal villous atrophy on biopsy (even if asymptomatic gastrointestinally)
- Celiac disease causes malabsorption predominantly in the proximal small bowel (duodenum and jejunum), where iron, calcium, folate, and fat-soluble vitamins (A, D, E, K) are absorbed; this explains the characteristic pattern of deficiencies
- Celiac disease clusters with other autoimmune conditions — especially type 1 diabetes (5-10% prevalence), autoimmune thyroiditis (5-7%), and autoimmune liver disease; first-degree relatives have a 10% prevalence and should be screened