Age: 19.0
Sex: F
Vaccine: HPV4
Symptoms: Mood altered, Multiple sclerosis, Muscle atrophy, Musculoskeletal pain, Neurological examination
Clinical narrative: Case received from a lawyer on 28-JUN-2011. The case was linked with the non serious case E2011-04039 (WAES#1109USA01948, reaction after D1). A 19 year old female patient had received a third dose of GARDASIL (lot number: 0276U; batch number: NF58550) on 28-DEC-2007, injection route and site not reported. "Short time later, from one day to the next" the patient was unable to walk even with the help of crutches. All her joints were swollen and the corresponding inflammation parameters in the blood were increased. The patient was diagnosed with "rheumatic disease". At the time of reporting, the patient was hardly able to do activities of daily living. Reportedly, all joints were affected with the disease. Previous doses of GARDASIL were given on 04-JUN-2007 (D1: lot number: 655671/1024F; batch number: NE51790) and on 13-AUG-2007 (D2: lot number: 655671/1024F; batch number: NE51790). Patient suffered from significant abnormal vision and fever after D1. Duration was not reported (see case E2011-04039 (WAES#1109USA01948)). Toleration of D2 was not reported. Follow-up was received on 05-SEP-2011. The lawyer provided patient's questionnaire dated 07-AUG-2011, the patient-doctor confidentially declarations dated 18-AUG-2011 and the patient's vaccination certificate. In the questionnaire, the following symptoms were mentioned: joint swelling, joint pain, visual disturbance. Onset of the first symptom(s) was reported to be on 05-JUN-2007 (i.e. one day after the first dose of GARDASIL). It was unclear, however, if only visual disturbance (as initially reported) or also joint symptoms started at that time. Diagnosis of rheumatic disease was made on 26-MAY-2008. On 28-SEP-2010, the patient experienced optic neuritis (duration and outcome not reported). It was also stated that the patient had a history of Alport's syndrome (diagnosed in 1995). Family history of rheumatic diseases was negative. Concomitant medication included an oral contraceptive, AIDA, no exact start date reported. Names and addresses of several different treating physicians/hospitals were provided. Follow-up information received on 27-SEP-2011 and 28-SEP-2011: Hospital records of a rheumatological centre were received (hospitalisation 05-SEP-2008 to 18-SEP-2008). The patient had a car accident in 2006 or 2007 with trauma of her left shoulder (no fracture), probably causing an impingement syndrome. Reportedly, joint pain started "over night, about 3.5 months prior to hospitalization". The family doctor had made several lab tests (among them remarkable IgA antibody titre against Yersinia). Under treatment with antibiotics (Penicillin V for 10 days) the symptoms had almost resolved, but are still persisting only in the knee joints. 2.5 weeks prior to the hospitalization, the patient additionally developed afflictions in the lower lumbar spine. Treatment with NOVALGIN, Paracetamol and Ibuprofen were unsuccessful, she then received TRAMAL. Clinical examination upon admission only showed mild tenderness at the knee joints and retropatellar crepitation. Sonogram of the knee joints showed chondromalacia and retropatellar slide bearing with lateral patella deviation tendency. No inflammatory signs (arthritis) were seen. The patient was treated with NSAID's (IBUPROFEN) and predominantly had physiotherapy and balneotherapy. It was pointed out that a part of the patient's complaints could not be dedicated to the reactive arthritis but the chondromalacia. At the time of discharge she was nearly free of complaints, with continuing medication of Ibuprofen if needed. On 23-OCT-2008 a CT of the right knee was carried out which was unremarkable (signal enhancement of the inner meniscus was not interpreted as a meniscopathy grade I but read as the fibrovascular bundle. From 07-APR-2009 until 16-APR-2009 the patient was re-hospitalised in the same rheumatological centre due to ongoing pain especially in the knee joints. Prior to hospitalisation, the patient had medication with TARGIN. X-ray of both shoulder joints, both hands and both feet showed no pathologies. As an overall picture, taken into account all the technical, clinical and laboratory exams, a rheumatic spectrum disorder could be ruled out. Symptoms still corresponded to femoral patellar pain syndrome caused by chondromalacia. Again, the patient had physiotherapy, balneotherapy, cryotherapy, massages, kinesiotapes on both knee joints and also psychological group therapy sessions. Further inpatient treatment in an orthopaedic or rheumatologic centre was not deemed medically sensible. Instead, a stay in a psychosomatic clinic was suggested as a abnormal toleration of pain with a tendency to somatisation was evoked. An re-integration into employment was strongly recommended. Outpatient controls from 03-JUN-2008 until 03-SEP-2009 in a specialized practice for rheumatic diseases showed increased CCP (cyclic citrullinated peptide) antibodies on 03-Jun-2008 (18.98 RE/mL). Negative results were obtained for HLA-B27, Borrellia and Chlamydia (IgG and IgM), CRP, rheumatic factor, ANA (1:160), and centromere antibodies. Yersinia IgG negative, borderline for IgA (36 KDa). Increased CCP was discussed as a possible incipient inflammatory rheumatic disease, albeit this result was never controlled. Follow-up information received on 04-OCT-2011. Reports of two neurosurgical consultations in a "vertebral column centre" were provided. On 21-OCT-2008, the patient complained of pain was radiating to the left leg. Clinical exam showed normal reflex status, negative Lasegue's sign, but bilateral painful sacroiliac joints and facette joints. The vertebral magnetic resonance imaging (MRI) showed a "black disc" on L5/S1 with medical intervertebral disc protrusion, but with subligamental hold. The muscle relief in the L5/S1 segment was missing, there is a fatty degeneration of the back muscles. Intensified physiotherapy with equipment was recommended. Check-up on 09-JUN-2009 confirmed previous diagnosis, only slight improvement was seen after 18 sessions of physiotherapy. It was stated that, given the fact that the patient was working as a measurement engineer, the complaints were considered to lead to a reduction of earning capacity. Follow-up information was received on 12-OCT-2011. Two neurological outpatient reports and report of a Magnetic resonance imaging (MRI) of both knees were provided. On 20-AUG-2008, during a neurological consultation the patient reported that at the same time as her having an infection in May 2008 she had developed pain in upper and lower extremities. Under treatment with antibiotics the pain in the upper extremities had improved, but was persisting in the lower extremities with emphasis on right. In addition she also experienced intermittent lumbar pain. A lumbar MRT showed disc protrusion on L5/S1 without stenosis, an electromyography showed no evidence of neurogenic damage of the right innervated muscles between L3 to S1. On 25-FEB-2009, during a control neurological consultation the patient complained of continuous pain of the right knee and a stress test showed noticeable motor weakness. Electromyography showed no evidence of a new or florid radicular neurogenic damage of the right muscles between L3 and S1. On 06-FEB-2009, a MRI of both knees showed degenerative damage of the posterior horn meniscus on both sides. No new rupture and no effusion were noted. The same radiologist had performed a MRI of the right knee on 13-OCT-2008 (see follow-up 27/28-SEP-2011 with corrections), but it was not made reference to the previous examination). Follow up on 19-DEC-2011: a short note from a rheumatological centre was forwarded. It was reported that the patient presented at the rheumatologic outpatient department on 03-AUG-2011. She complained of multiple arthralgia. The clinical examination did not reveal joint swellings, the joints were generally "subjective painful". Diagnosis was "multiple arthralgia without verifiable clinical findings". It was stated that a relation between GARDASIL and joint swelling could be ruled out as far as possible. Follow up on 30-DEC-2011: multiple medical records and hospital reports were provided (most of them were already known). New event of palindromic rheumatism was added. Medical history included a positive antistreptolysin test (qualitative) on 13-JUL-2005. On 26-MAY-2008, antistreptolysin quant. test (quantitative) was 410. On 03-JUN-2008, cyclic citrullinated peptide was 18.98, antinuclear antibodies (ANA) (IF) titer was 1:320. On 09-SEP-2008, ANA screening (IgG) was 1:160, infection screen showed Yersinia enterocolitica IgG 41 and IgA 12. In June 2011, diagnosis of palindromic rheumatism was used for the first time in the documents by the treating rheumatologist. Due to persisting arthralgia, the patient was again hospitalized from 22-AUG-2011 until 12-SEP-2011. On admission, blood count showed haemoglobin of 10.5 and haematocrit of 31.7%. Between 23-AUG-2011 and 30-AUG-2011 the patient received treatment with LYRICA 25 mg at night. It was also stated that the patient was self medicating with various herbal/homeopathic medicines (harpagophytum procumens, vitamins and amino acids). During hospitalization, the patient sometimes requested a wheelchair as she was unable to walk without assistance. Follow-up information was received on 23-JAN-2012. Multiple medical records and hospital reports were forwarded. Medical history include car accident on 07-May-2007 (car overturned three times), on 10-MAY-2007 a cranial CT was unremarkable. On 06-AUG-2007 the patient attended the ophthalmological outpatient department due to contusion bulbi after the car accident, result was unremarkable. Concomitant medication included enalapril and ORGAMETRIL in 2005. On 29-MAY-2009 autoimmune diagnostics showed negative results for ANA; C-ANCA and P-ANCA. On 15-MAY-2010 the patient had an ophthalmological appointment. Examination raised suspicion of Sjogren syndrome and a rheumatological clarification was recommended. On 03-JAN-2010 a visual field examination at the ophthalmological department showed positive progression and no further therapy was necessary. From 21-MAR-2011 until 26-MAR-2011 the patient was hospitalised and therapy with plasmapheresis was performed for 6 times because of retrobulbar neuritis. The report stated that medical history and clinical findings were still indicative of retrobulbar neuritis on the right. On 19-MAY-2011 the patient attended the ophthalmological department due to worsening of the eyesight on the right. A worsening of the visual field indicated a recurrent retrobulbar neuritis. On 05-JUN-2011 lab tests showed normal values for C-reactive protein <5 mg/l, C3-complement = (1.12 g/l) and C4-complement = 0.226 g/l. On 28-SEP-2011 the patient presented at the emergency department due to recurrent worsening of visual field on the right. Medication at that time included PREGABALIN, novalgin and an oral contraceptive. It was the first time that a suspicion of multiple sclerosis was raised. The next day the patient was seen at the ophthalmological outpatient department with suspicion of recurrent retrobulbar neuritis. Examination showed no changes in comparison to previous examination in May 2011. On 28-OCT-2011 the patient attended the emergency department due to colour vision abnormality and suspicion of MS was again raised. The patient was referred to the neurological department. A neuro-immunological consultation was recommended. Follow up information received on 02-MAR-2012. The patient was hospitalized from 05-JUN-2011 until 11-JUN-2011 for treatment with plasmapheresis (five times). At the time she complained of headache and had another retrobulbar neuritis. Follow-up information received on 28-JUN-2012. Patient was admitted to a psychiatric day-hospital from 26-JAN-2009 to 27-MAR-2009, report was provided. Patient's mother had a medical history of depression. On admission the patient complained about mood changes, tenseness as a result of chronic pain, sleep disturbances, loss of appetite and interests and decreased libido. Depressive development in the scope of reactive arthritis and Alport Syndrome was diagnosed. Treatment program was sometimes interrupted due to painful episodes with dissociative disturbances. In pain-free intervals the patient attended treatment program very well. Depression improved and no pharmacological treatment was necessary. On 27-MAR-2009, she was discharged in a partly stabilised condition. Long-term outpatient psychotherapy was recommended. ECG was performed on 28-JAN-2009, and showed no pathologies. Follow-up information received on 29-JUN-2012. A short memorandum was forwarded by patient's lawyer (patient presented to his office on 26-JUN-2012). It summarizes the patient's state of health that had slightly improved. At the time of reporting she needed a wheelchair as she could not walk longer distances and became tired. Additionally she had an impaired vision, in particular on the right side of her face. Furthermore, she suffered from pain on the right side of her face. She was no longer able to work in her job. The report also informs that the patient's pension application has been preliminary accepted until 31-JAN-2013. On 02-JUL-2012, an ophthalmologic report from investigation on 09-MAR-2012, was provided. The patient presented with subjective aggravation of visual field impairment of right eye three to four weeks earlier. Physician did not see an indication for a new acute episode of retrobulbar neuritis. Other business partner number included: E2011-03967. No further information is available.