Age: 16.0
Sex: M
Vaccine: HPV4, HPV9
Symptoms: Osteoporosis, Pain, Pain in extremity, Palpitations, Postural orthostatic tachycardia syndrome
Clinical narrative: Mast Cell Activation Syndrome; Postural orthostatic tachycardia syndrome; Inappropriate schedule of vaccine administered; This literature marketed information has been received from the authors in a published article title as stated below and refers to a 20-year-old male patient. The patient had been healthy and athletic.  On an unspecified date, he receipt of his first dose 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 dosing at 16 year-old. However, on an unspecified date, two weeks after he received his second dose of Gardasil, at 18 years old, he began feeling sick in general and began experiencing unilateral knee redness and stiffness as well as a more generalized burning rash for the next three months. He managed to continue with work and school, though. Five months after the second Gardasil injection, during a check-up at which he complained about the knee pain and burning rash for the last few months, he received the third injection. Two days later, he heard his knees "pop" and felt his knees become weak and unable to bear his weight. He also developed burning pain in the legs, difficulty walking, and general fatigue. Efforts to "push" himself beyond his fatigue only made him feel even worse. By one month after the third injection, he required a cane to walk. At initial evaluation, he described having "weak knees;" burning pain in his arms, face, and occasionally in the legs; numbness in his face, hands, and arms lasting from a few minutes to 1.5 hours; intermittent light-headedness and palpitations; recurrent headaches; difficulty concentrating and word-finding difficulty; and fatigue. He denied significant gastrointestinal (GI) disturbance or urinary symptoms. He reported weight loss of 20 pounds over a period of a few weeks after he initially got sick, but he then was able to regain that weight. Due to his symptoms causing significant functional impairment, he had to take a leave of absence from college and also had to stop working. He had consulted many specialists, including a rheumatologist who diagnosed him with fibromyalgia. He was tried (at different points) on duloxetine and amitriptyline, which did not help. A tilt table test at age 20 was positive, and a diagnosis of postural orthostatic tachycardia syndrome (POTS) was made; he was instructed to increase salt and fluid intake, which he felt improved his light-headedness. At the time of initial evaluation, his walking was limited to 30 minutes due to knee pain and fatigue. Bone densitometry unexpectedly showed severe osteoporosis (T scores -4.0 and -4.1 in the bilateral hips). Evaluation by a geneticist for a question of Marfan syndrome was negative; whole exome sequencing was pursued, too, and was negative. Additional consultations were pursued with five endocrinologists, a rheumatologist, a metabolic bone disease specialist, and two orthopedic surgeons, all with no additional diagnostic insights. Due to persistent arthralgia causing difficulty walking and evidence of small fiber neuropathy (SFN) on quantitative sudomotor axon reflex testing (QSART), he was started on intravenous immune globulin (IVIG) at 2 g/kg every three weeks and experienced rapid, significant improvement in burning pain, weakness, joint pain, and ambulation; he was able to gain some weight, too. However, episodes of tachycardia, rashes, and severe osteoporosis all persisted, and the symptoms improved by IVIG reliably relapsed before his next IVIG dose was due. Laboratory testing for mast cell activation was significant solely for a plasma histamine level of 2.8 ng/ml (normal = 1.8). Labs were also notable for mild decreases in serum copper (58 mcg/dl, normal 70-140) and iron (50 mcg/dl, normal 59-158) and low vitamin D (15 ng/ml, normal 30-100). His vitamin B12 level was low normal (208 pg/ml, normal 200-910). Adrenergic and muscarinic antibodies were negative. Antihistamines gained him some improvements, but IVIG has persisted as his most effective intervention.  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.