A curious case of depression
Mr. Z, age 61, has a history of bipolar I disorder and presents with worsening depression, fatigue, thrombocytopenia, and a rash. What is exacerbating his symptoms?
| Cerebrovascular disease |
| Degenerative disorders (Parkinson’s disease, Huntington’s disease, Wilson’s disease) |
| Demyelinating disorders (multiple sclerosis, amyotrophic lateral sclerosis, lipid storage disease) |
| Endocrine disorders (Addison’s disease, Cushing’s disease, hyperthyroidism, hypothyroidism, hyperparathyroidism, pituitary dysfunction) |
| Epilepsy |
| Infectious diseases |
| Immune diseases |
| Metabolic encephalopathy |
| Neoplasm |
| Nutritional deficits (thiamine, niacin, vitamin B12) |
| Primary psychiatric disorders (mood disorders, dementia, sleep disorders) |
| Substance use |
| Toxins/medications |
| Traumatic brain injury |
| Source: Reference 1 |
Possible infectious causes
The increased prevalence of immune suppression due to human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) or from therapeutic modalities such as cancer therapy or splenectomy has led to an increased number of chronic CNS infections, manifesting with an array of neuropsychiatric symptoms and nonspecific physiological reactions.1,7 Mr. Z complains of a 2-month period of worsening depression that could suggest an infectious process with an insidious onset. Some infectious agents that can cause chronic CNS infection and encephalopathy are presented in Table 2.8 HIV, tuberculosis, syphilis, Lyme disease, and herpes simplex virus are becoming more prevalent and can present with neuropsychiatric symptoms.1 For example, in addition to thrombocytopenia and low-grade fever, patients with HIV may exhibit a broad range of neuropsychiatric symptoms such as cognitive problems, impaired executive and motor functioning, sleep disturbance, and anxiety. These patients frequently present with low mood and neurovegetative symptoms of depression.7 Similarly, the same tick responsible for Lyme disease infection can transmit other infectious agents that can cause thrombocytopenia, including Babesia, Ehrlichia chaffeensis, Anaplasma phagocytophilum, and human Ewingii ehrlichiosis.
The authors’ observations
Diagnosis of a mood change, particularly an MDE, is clinical, based on careful psychiatric evaluation using standardized criteria rather than a specific lab test. However, some laboratory studies (Table 3)1 are useful in differentiating medical illnesses that may present with depression. Mr. Z’s presentation warrants investigating these tests. His history of traumatic splenectomy and night sweats suggests an infection. The team’s initial recommendations include laboratory tests, discontinuing divalproex because it may be causing thrombocytopenia, and decreasing risperidone to 2 mg/d to improve his fatigue and possibly developed extrapyramidal symptoms.
Table 2
Potential infectious causes of chronic encephalopathy
| Type of infection | Organism/disease |
|---|---|
| Mycobacterial | Mycobacterium tuberculosis |
| Spirochetal | Treponema pallidum (syphilis), Borrelia burgdorferi (Lyme disease), Leptospira |
| Bacterial | Brucella, Listeria, Nocardia, Actinomyces israelii, Whipple’s disease |
| Viral | HIV/AIDS, cytomegalovirus, varicella zoster virus, herpes simplex virus, enterovirus |
| Fungal | Histoplasmosis, coccidiosis, sporothrix, Blastomyces, Cryptococcus |
| Parasitic | Toxoplasmosis, taenia solium (cysticercosis), Schistosoma, Acanthamoeba |
| AIDS: acquired immunodeficiency syndrome; HIV: human immunodeficiency virus Source: Reference 8 | |
Table 3
Differentiating medical illnesses that may mimic depression
| Laboratory tests |
|
| Imaging studies |
|
| Other tests |
|
| Procedures |
|
| ABG: arterial blood gases; CBC: complete blood count; EEG: electroencephalogram; ELISA: enzyme-linked immunosorbent assay; HIV: human immunodeficiency virus; VDRL: venereal disease research laboratory Source: Reference 1 |
TREATMENT: Cause revealed
Mr. Z develops a persistent fever of 102°F with continuous profuse sweating and a hypotensive episode. Blood work reveals mild anemia, thrombocytopenia, and increased coagulation parameters with high D-dimer and low fibrinogen, consistent with diagnosis of disseminated intravascular coagulation (DIC) secondary to infectious etiology. Thyroid and HIV tests are negative. After further evaluation, Mr. Z remembers that 4 months earlier he removed several ticks from his legs after hunting; he also remembers experiencing shivering and night sweats several weeks before he was hospitalized. His blood smear is positive for babesiosis and further testing confirms positive Lyme antibodies. Mr. Z is started on aggressive hemodynamic stabilization and a pathogen-tailored course of antibiotics for several weeks. This results in improvement and discharge home in a stable condition. His depression and fatigue improve but do not fully remit by the time he is discharged.
The authors’ observations
Lyme disease is one of the fastest-growing infectious diseases in the United States.9 The prevalence of positive Lyme antibodies is 30% higher in psychiatric populations than the general population.10 Lyme disease is transmitted by deer tick bite, often undetected, that is infected with spirochete Borrelia burgdorferi. To be infectious, ticks need to be attached to the skin for 24 to 48 hours,11,12 although individual cases have reported transmission in <24 hours. The clinical manifestations of Lyme disease can be divided into 3 phases:
- early localized phase, characterized by the distinctive skin lesion erythema migrans with or without constitutional symptoms
- early disseminated phase, characterized by multiple erythema migrans lesions and neurologic and/or cardiac findings
- late or chronic disease associated with intermittent/persistent arthritis and/or neurologic problems.11,13
