Age: 19.0
Sex: F
Vaccine: HPV4, HPV9
Symptoms: Histamine level increased, Human herpes virus 6 serology positive, Hyperacusis, Insomnia, Laboratory test abnormal
Clinical narrative: Mast Cell Activation Syndrome; This literature marketed information has been received from the authors in a published article title as stated below and refers to a 27-year-old female patient. She reported having been noticed by her mother at birth to have somewhat enlarged genitalia. Dermatographism was apparent from early in infancy; she was very sensitive to certain clothing and tags. Her sleep cycle has been unusual her entire life, dating to infancy: At age 2 years-old, normally active and verbal, she developed a severe reaction to her fourth Tdap (tetanus, diphtheria, pertussis) vaccine, a global paresis (unable to walk) and aphasia which lasted several hours and spontaneously resolved. The reaction was attributed to the pertussis component of the vaccine, so the next vaccine she received in this series was diphtheria, tetanus (DT) without pertussis, and no reaction was seen. Early in childhood, she developed cold-induced asthma and an episode of hyperactivity after ingesting a red-dyed food. She began manifesting frequent/chronic ear infections and headaches as well as recurrent stomach pains and nausea, which were attributed to alleged, but never proven, lactase deficiency. At 11 years old, menarche was unremarkable. She was otherwise "healthy" until age 14, when she developed a "post-viral syndrome". Following a non-specific viral-like illness, she experienced severe fatigue and needed to nap for three hours after school. Photophobia and mydriasis emerged and have persisted ever since. Severe dysmenorrhea emerged, and an oral contraceptive was started for presumed endometriosis. Migraines, Raynaud's phenomenon, presyncopal spells (typically orthostatic), and intermittent urticaria to hot water also emerged. Fatigue eased somewhat over months (she felt she was "very functional" for the rest of high school) but was circadian, worse in the mornings. At 16 years-old, she had her first syncopal episode and could no longer stand in one position for any significant time without becoming pre-syncopal. At 18 years old, in her first year at college, she developed episodes of stabbing leg pains, paresthesias in her extremities, and chest pain at the superior aspect of the rib cage, all of which have persisted ever since, though frequency diminished later with treatment for a diagnosis of Lyme disease (no tick bite or bull'seye rash was ever seen). Also, in her first semester at college, she developed frequent aphthous oral ulcers and scalp folliculitis. She then "fell apart" during her second semester. She developed severe brain fog and fatigue, could no longer keep up with her schoolwork, and had to return home. She was soon diagnosed with mononucleosis and then Lyme disease. She took a short course of doxycycline but had difficulties tolerating it. She completed her schoolwork that semester from home with difficulty. Still symptomatic, she returned for her sophomore year. Family history was notable for a younger sister who had polycystic ovarian syndrome (PCOS), a long history of chronic idiopathic urticaria, and presumptive mast cell activation syndrome (MCAS). In addition, her mother had recently been diagnosed with MCAS.  On an unspecified date, in the spring semester, the patient was vaccinated with unidentified Merck hpv vaccine administered, also reported as Gardasil (Lot #, expiration date, dose, route of administration and anatomical location of vaccine were not reported) for prophylaxis, she received the series of three Gardasil vaccinations. One month after her last vaccination, she received the Yellow Fever vaccine to prepare for a school-related trip but only had some local erythema to this vaccination. She traveled two months later (i.e., three months following her last Gardasil vaccination) and soon developed severe gastritis. She then soon developed a severe ear infection with rupture of the tympanic membrane and was treated with an antibiotic. Soon after the ear infection, she developed more brain fog and fatigue, albeit with different senses of these symptoms than previously experienced. Post-prandial tachycardia episodes and worsening of fatigue emerged. She became "more sensitive" to her environment in general, including odors, sounds, and lights. Headaches worsened. She increasingly needed social isolation. At 20-years old, she was re-treated for Lyme disease with high-dose amoxicillin, with little apparent benefit. At 21-years-old, in her senior year in college, she developed severe motion sickness, which has persisted ever since. Severe chemical sensitivities emerged and have persisted ever since. At 24 years-old, she noticed she had become completely intolerant of alcohol. Because of increasing gastrointestinal symptoms as well as a new diagnosis in her younger sister of non-celiac gluten intolerance, she decided to try a gluten-free diet, and though she lost weight, frequent nausea and bilious vomiting emerged, sometimes unrelated to food intake. She also developed aquagenic urticaria and cystic acne, which have persisted, waxing and waning, ever since. At 27-years old, she suffered a pneumonia, requiring a course of azithromycin. Soon after, on initial evaluation, she reported severe fatigue, weight loss with cyclical vomiting, diarrhea with mucus, migratory joint pain, worsening facial and scalp cystic acne, trouble with concentration and memory, insomnia, increased urinary frequency, and mild alopecia. She also noted tachycardia and worsening concentration after meals that was so disruptive that she had to avoid eating before important assignments/tasks. Physical examination was unremarkable. Laboratory evaluation was notable for a low normal vitamin B12 level, mild folate deficiency, mild vitamin D deficiency, a mildly elevated high-sensitivity C-reactive protein (hsCRP), elevated herpesvirus 6  (HHV-6) IgG at 1:1280 but negative HHV-6 viral load by polymerase chain reaction (PCR), normal amylase and lipase, normal tryptase, a mildly elevated chromogranin A level (103 ng/ml, normal 0-95), a mildly elevated plasma histamine level (2.0 ng/ml, normal < 1.8), and a normal 2-4hour urinary N-methylhistamine level. Hormone testing, including evaluation for congenital adrenal hyperplasia, was negative. MCAS-targeted therapy was initiated with trials of various non-sedating H1 blockers. Loratadine 10 mg twice daily served her best but only provided some help for intermittent congestion. Ranitidine and famotidine both seemed to cause alopecia; she did not try any other H2 blockers. Oral Cromoglicic acid (CROMOLYN) 200 mg twice daily improved her nausea and vomiting, and her weight has stabilized. Medical marijuana, taken occasionally, also helps with symptom flares. She started low-dose naltrexone (LDN) and found 4.5 mg daily to be her optimal dose. Her hsCRP normalized. She has persistent fatigue and insomnia, worse in the spring. She was continuing with other MCAS-targeted medication trials.    Literature report:  Upon internal review the of Mast Cell Activation Syndrome (MCAs) was considered as medically significant.   This is one of several report from the same literature article.   A copy of the published article is attached as further documentation of the patient's experience.