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From Medscape Rheumatology > Rheumatology Curbside Consult
Swelling, Pain, and Pancytopenia: An Elusive Diagnosis
Stephen Paget, MD
[hr]

A 26-year-old woman presents for an evaluation and better definition of a 3-year history of progressive abdominal pain and distension, fatigue, pancytopenia, leg swelling, and pain.
Past Medical History

The patient has already had an extensive work-up at many of the best institutions in the country, but no specific diagnosis has been made, nor has any therapy been recommended.

Pertinent features of the evaluation follow:

Physical examination previously demonstrated normal vital signs, no weight loss, no synovitis, mild edema of the legs up to the mid calves, abdominal distention and diffuse direct tenderness, normal muscle strength, and no muscle tenderness.
Laboratory tests included: white count 1900 with an absolute neutrophil count of 800; hemoglobin 10.5; platelet count 140,000; normal renal and liver function tests; and normal CK, amylase, and lipase. ESR was 20 and CRP was 1.0.
Two bone marrow analyses showed normal marrow elements but increased scarring demonstrated by fibrillar material with negative stains for amyloid. This type of abnormality is thought to be related to ischemia and has been found in patients with cancer, malnutrition, the antiphospholipid syndrome, and, rarely, autoimmune disorders.
Abdominal evaluation has included a normal upper and lower endoscopy, appropriate celiac serologies and bowel biopsy, Whipple disease assessment, and CAT scan of the abdomen and pelvis with oral contrast.
Normal renal function, albumin, 24-hour protein, and renal sonogram.
Normal cardiac and pulmonary testing including an EKG, echocardiogram, chest x-ray, and chest CT with contrast.
Negative autoimmune serologies, including ANA and antibodies to dsDNA, Sm, RNP, SSA, SSB, SCL-70, and Jo1.
Normal serum protein electrophoresis, immunoelectrophoresis, and urine for Bence Jones protein.
Negative infection workup, including tests for EBV, CMV, toxoplasmosis, hepatitis A, B and C, HIV, septicemia, TB, fungal disease, Borrelia, ehrlichiosis, babesiosis, leptospirosis, and Lyme disease.

My Evaluation

When I saw the patient I was impressed by her normal vital signs, stable weight, marked abdominal distension with mild direct tenderness, muscle tenderness in the thighs and calves, 4+/5 strength in the legs and arms, mild edema to the mid calves (she notes that her legs swell as the days goes on), lack of synovitis, and the absence of rash or adenopathy. Cardiac, pulmonary, ophthalmologic, neurologic (except for the muscle examination), and HEENT examinations were normal.

Laboratory Tests: WBC 2200 with an ANC of 1000, hemoglobin 10.2 with normal red cell volumes and peripheral smear, platelets 120,000, ESR 20, CRP 0.7. AST was 180 and ALT 200, with a normal GGTP 20, alkaline phosphatase, and bilirubin. Albumin was 4.0.
Overview at This Time

Obviously, in a patient with a chronic, systemic illness like this, the usual differential needs to include infection, cancers, and autoimmune disorders. Immediately, though, infection and cancer go down on the list as likely causes of her illness simply because of the disease duration of 3 years.

Key findings included:

Personal/social: She seemed quite reliable, bright, and frustrated. She had to stop working as a teacher mostly because of her severe abdominal pain and distension.
Muscle: Clearly, she presents with muscle weakness and tenderness along with abnormal muscle tests including AST and ALT. I call them muscle tests in this situation because they do arise in both the muscle and the liver, and the rest of her liver function tests were normal.
Leg edema without signs or symptoms of congestive heart failure, renal disease, or protein loss.
Prominent abdominal distension; no organomegaly, weight loss, or history of diarrhea.
Lack of synovitis.

My Diagnosis

I believe this patient has an autoimmune disorder manifested by muscle weakness due to myositis, pancytopenia due to bone marrow necrosis and autoimmunity, leg edema due to inflammation-related capillary leak and myositis, and probable intestinal dysmotility.

Note that I make this diagnosis despite the normal serologic tests over the years. Oftentimes, diagnoses of autoimmune disorders are made on clinical grounds. Laboratory tests are often confirmatory but are not mandated to be abnormal in the face of a strong clinical presentation and an extensive work-up that has ruled out malignancy and infection.

Infection and malignancy seem quite unlikely here.
Further Work-up

Muscle: CK elevated at 800, aldolase elevated at 28. Right quadriceps ultrasound showed diffuse edema, consistent with inflammation. Needle muscle biopsy: myositis
Autoimmune serologies continue to be negative.
Hydrogen breath test abnormal. This finding is consistent with bacterial overgrowth, likely related to autoimmune disorder-related bowel dysmotility.

Treatment Approach

1. Myositis and cytopenias: The patient was placed on methylprednisolone 12 mg twice daily. This lowish dose was chosen initially because of the bowel disorder and my concern about infection. After 1 week on this dose, muscle weakness and tenderness, muscle enzyme tests, and edema cleared completely. Also the patient's white blood cell count rose to 8500, platelets to 220,000, and hemoglobin to 12.

2. Bacterial overgrowth: The patient was placed on rifaximin for the treatment of bacterial overgrowth.
Take-Home Messages

1. Wrong diagnoses for 3 years -- Despite being seen in the "best" institutions, this woman's diagnosis remained elusive. Because of her thin habitus (a family trait), her bone marrow findings were attributed to an eating disorder, her abdominal problem to irritable bowel syndrome, and her muscle symptoms to fibromyalgia! You owe it to the patient to address her problems anew and with a fresh approach. Don't be dissuaded by "experts" who are fallible.

She noted that her muscle, edema, abdominal, and blood count abnormalities began at the same time, a clue to the fact that they were all connected (ie, a systemic disorder rather than a plethora of multiple disorders, some of which were considered psychogenic). You must review all records even though the best people in the world have already seen and passed on them.

Remember, patients "don't read the books," so even though some parts of the problem don't jive with others, it is a total story that should be considered.

2. Autoimmune disorders -- While most autoimmune disorders of this degree and chronicity will be associated with abnormal serologies, this is not true 100% of the time. You have to keep an open mind and trust yourhistory, physical, and review of the records.

3. You are the captain of the ship -- You need to keep your consultants up to date and on the same page so things don't fall through the cracks.

4. You must communicate with and listen to your patient -- This patient was "branded" from the word go. Had someone actually listened, she would not have had to go through 3 years of test after test without an answer.