A 14-year-old boy was in his usual state of good health until October 2015, when he developed psychiatric symptoms including feeling overwhelmed, confused, depressed, and agitated. He said that he was an "evil, damned son of the devil" and wanted to kill himself because he was afraid of his new-onset homicidal thoughts toward those he cared about. In October 2015, he was admitted for emergency psychiatric hospitalization at a local hospital and was placed on aripiprazole for major depressive disorder (MDD) with psychotic features. He was discharged after 1 week, still somewhat psychotic but no longer suicidal or homicidal.
His early history was unremarkable except for an episode of depression in the 3rd grade (9 years of age) that the parents attributed to his feeling unchallenged in school and being bullied by peers, as he was very bright, but socially awkward. Placement on sertraline 25 mg for 1 year plus transfer to a small school for gifted children resulted in complete remission. The evaluating psychiatrist noted the possibility of Asperger's syndrome as a secondary diagnosis. In April 2014, he was treated with antibiotics for Mycoplasma pneumoniae with a recurrence and retreatment in December 2014.
In June 2015, he was treated with topical steroids for poison ivy and an oral cephalosporin for multiple bug bites, obtained while visiting a farm in Missouri. The family history was positive for depression and alcohol abuse on both sides of the family tree, possible bipolar disorder, compulsive gambling, and possible attention deficit hyperactivity disorder (ADHD): maternal side:ulcerative colitis, fibromyalgia in 2 relatives, and rheumatoid arthritis; paternal side:multiple sclerosis and adult-onset diabetes mellitus.
Historically, prior to psychiatric symptom onset, the boy was socially, athletically, and academically active, as evidenced by participation in national geography and history competitions, and a lead actor in a school play, winning an award in fencing and achieving excellent course grades. In the context of animal and arthropod exposures, the family resided in a Midwestern state, in suburban housing, and had multiple pets: cats, a dog, a spotted gecko, and a giant African millipede. Two cats were adopted as strays in 2010, 1 of which had an open wound over his back requiring treatment. A visiting dog infested with fleas entered the household in 2011. The boy had sustained cat bites and scratches prior to illness onset. Outdoor activities consisted of gardening and hiking. In addition to fleas and ticks, his parents reported exposure to mosquitoes and spiders. He had traveled in northeastern, southeastern, and western states. International travel was limited to 2 trips to Mexico in June 2013 (family vacation) and July 2015 (mission trip to impoverished areas).
Weeks after initial hospitalization in October, he became more dysfunctional; school was not possible; he developed progressively severe psychiatric symptoms including obsessional intrusive thoughts, phobias, irrational fears, emotional lability, unpredictable rage outbursts, and increased psychotic thinking. He believed that he had special powers and that a family cat wanted to kill him. By December 2015, his illness had progressed in severity, causing his mother to quit her job to provide full-time supervision. In addition to persecutory delusions related to his pets, he developed auditory, visual, and tactile hallucinations and began refusing to leave the house. A second psychiatric hospitalization occurred in December 2015.
In January 2016, following discharge after a week-long hospitalization, he developed non-specific somatic symptoms, including excessive fatigue, daily headaches, chest pains, shortness of breath (possible panic anxiety), and urinary frequency. Figure 1 depicts a timeline including major medical interventions, physician consultations, and hospitalizations, during which he was treated with multiple different psychotropic medications including antipsychotics, mood stabilizers, antidepressants, and benzodiazepines, often in combination with other pharmacologic agents (Figure 2). Two local psychiatrists diagnosed schizophrenia.
In the summer of 2016, he was hospitalized for 11 weeks at a large out-of-state psychiatric teaching hospital where extensive testing, including inflammation markers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]), a Mayo Clinic Encephalopathy Autoimmune Evaluation Panel, voltage-gated potassium channel antibody testing, an electroencephalogram (EEG), and a brain magnetic resonance imaging (MRI) were performed, all of which were considered unremarkable. Provisional discharge diagnoses were schizophrenia and obsessive-compulsive disorder.
After returning home in August 2016, the parents noted cutaneous "stretch marks." Although he remained quite ill, his parents refused psychiatric re-hospitalization in favor of in-home treatment. In October 2016, a consulting neurologist proposed the diagnosis of autoimmune encephalitis based on a positive antinuclear antibody (ANA) titer (1:320), increasing CRP levels = 1.03 (Nl < 0.30 mg/dL) on August 31 and 1.96 on October 11, as well as increased CSF gamma interferon level = 6.0 (Nl < 4 pg/mL). His CSF neopterin value was 2.0 nmol/L (NI < 16.5 nmol/L).
An outpatient lumbar puncture was otherwise unrevealing. He was treated with rituximab infusion for autoimmune encephalitis, which decreased the duration and frequency of psychotic episodes; however, daily behavioral disruptions continued.
In January 2017, PANS was diagnosed based on historical symptoms (Table 1). Testing for Group A streptococcal infection, including antistreptolysin O titer, anti-DNase B titer, and other infections including M pneumoniae Immunoglobulin class G (IgG) and Immunoglobulin class M (IgM) antibodies, a Lyme enzyme-linked immunosorbent assay (ELISA) and Western blot IgG and IgM and viral titers were negative or equivocal. ANAs were not detected. When the evaluating physician observed the cutaneous "stretch mark-like" lesions on the boy's thighs and armpit (Figure 3), neurobartonellosis was proposed as a differential diagnostic consideration. Subsequent consultation with a dermatologist confirmed that cutaneous lesions were not oriented along the skin tension lines and the location and color were not consistent with striae and fluctuations in body weight. Histological examination of a 3-mm punch biopsy revealed sparse lymphohistiocytic dermal infiltration. Doxycycline monohydrate (100 mg BID) was administered. Preantibiotic Bartonella spp. diagnostic testing was not pursued.
In February, the parents requested that their son be entered into a research study approved by North Carolina State University's Institutional Review Board (Protocol No. 1960, Detection of Bartonella Species in the Blood of Healthy and Sick People).