Problem Representation
The patient is a 27-year-old man with a 9-year history of complex, multisystem symptoms including gastrointestinal issues, cognitive impairment, joint pain, skin rashes, and cardiac involvement, with elevated eosinophil counts, abnormal liver enzymes, and osteoporosis.
One Sentence Summary
A young man with a prolonged history of unexplained, multifaceted symptoms affecting various bodily systems, including gastrointestinal, neurological, dermatological, and cardiovascular, with laboratory findings indicating chronic inflammation and immune system dysregulation.
Prioritized Differential Diagnosis
- Single Most Likely Diagnosis
- Chronic multisystem autoimmune or autoinflammatory disorder: The patient's prolonged history of diverse symptoms affecting multiple systems, along with laboratory evidence of chronic inflammation (elevated IL-8, eosinophilia, and abnormal liver enzymes), suggests an underlying autoimmune or autoinflammatory process. The lack of a clear diagnosis despite extensive testing and the presence of autoantibody-negative results do not rule out this possibility, as many autoimmune diseases can be seronegative.
- Other Likely Diagnoses
- Mastocytosis: Although genetic tests for mastocytosis were negative, the patient had a skin biopsy showing increased mast cells, and his serum tryptase was normal, but urinary PGD2 was slightly elevated. Mastocytosis can present with a wide range of symptoms, including gastrointestinal issues, skin rashes, and cardiovascular symptoms.
- Eosinophilic Gastrointestinal Disorder (EGID): The patient's history of gastrointestinal symptoms, including upper GI pain, distension, diarrhea, and the finding of duodenitis on gastroscopy, along with fluctuating eosinophilia, suggests EGID. However, the lack of significant eosinophilic infiltration on biopsies complicates this diagnosis.
- Hypogonadism: The patient's sexual dysfunction, lack of facial hair, and borderline low testosterone levels suggest hypogonadism, potentially secondary to chronic illness.
- Do Not Miss Diagnoses
- Infectious diseases (e.g., parasitic infections, Lyme disease): Despite negative tests, the possibility of an infectious etiology, particularly given the patient's travel history and exposure to potential pathogens (e.g., Anisakis), should not be entirely dismissed without further consideration of less common pathogens or re-exposure.
- Lymphoma or other malignancies: Although the bone marrow biopsy was generally normal, the presence of chronic inflammation and immune system dysregulation increases the risk of lymphoproliferative disorders. Regular follow-up and monitoring for signs of malignancy are crucial.
- Rare Diagnoses
- Sarcoidosis: The patient's presentation with multisystem involvement, including potential lung (given the chest pain and myopericarditis), skin, and eye symptoms, along with elevated serum ACE levels, could suggest sarcoidosis. However, the lack of granulomatous inflammation on biopsies makes this less likely.
- Chronic active Epstein-Barr virus infection: Although the patient has a positive Epstein-Barr virus IgG, indicating past infection, rare cases of chronic active EBV infection can present with multisystem symptoms and should be considered in the differential diagnosis of patients with unexplained, prolonged illnesses.
Investigations That Haven't Been Done
- Further immunological testing, including assessment of T-cell subsets and function, to better understand the patient's immune system dysregulation.
- Repeat biopsies of affected tissues (e.g., gut, skin) to reassess for eosinophilic infiltration or other inflammatory changes.
- Consideration of advanced imaging techniques (e.g., PET/CT with different tracers) to evaluate the extent of inflammation and potential involvement of other organs.
- Genetic testing for rare immunodeficiency disorders or autoinflammatory syndromes not yet considered.
- Consultation with specialists in immunology, rheumatology, and gastroenterology to provide a multidisciplinary approach to diagnosis and management.