A new approach to the assessment of lumen visibility of coronary artery stent at various heart rates using 64-slice MDCT Coronary artery stent lumen visibility was assessed as a function of cardiac movement and temporal resolution with an automated objective method using an anthropomorphic moving heart phantom . Nine different coronary stents filled with contrast fluid and surrounded by fat were scanned using 64-slice multi-detector computed tomography -LRB- MDCT -RRB- at 50 -- 100 beats/min with the moving heart phantom . Image quality was assessed by measuring in-stent CT attenuation and by a dedicated tool in the longitudinal and axial plane . Images were scored by CT attenuation and lumen visibility and compared with theoretical scoring to analyse the effect of multi-segment reconstruction -LRB- MSR -RRB- . An average increase in CT attenuation of 144 ± 59 HU and average diminished lumen visibility of 29 ± 12 % was observed at higher heart rates in both planes . A negative correlation between image quality and heart rate was non-significant for the majority of measurements -LRB- P > 0.06 -RRB- . No improvement of image quality was observed in using MSR . In conclusion , in-stent CT attenuation increases and lumen visibility decreases at increasing heart rate . Results obtained with the automated tool show similar behaviour compared with attenuation measurements . Cardiac movement during data acquisition causes approximately twice as much blurring compared with the influence of temporal resolution on image quality . Introduction The introduction of multi-detector computed tomography -LRB- MDCT -RRB- has permitted the non-invasive visualisation of coronary arteries with sufficient temporal and spatial resolution . Moreover , MDCT has been used to research the assessment of coronary artery stent patency and discrimination between the presence of in-stent stenosis . Re-stenosis occurs in a substantial amount of patients which have been treated with stent implantation -LSB- 1 -RSB- . It has been shown that no direct visualisation of coronary in-stent re-stenosis is feasible using four-slice MDCT due to partial volume effects and beam hardening caused by metal artifacts of the stents -LSB- 2 -- 6 -RSB- . Recently it has been shown that despite some limitations 16-slice MDCT is sufficiently useful for the assessment and detection of in-stent restenosis in patients with a high accuracy in comparison with conventional coronary angiography -LRB- CAG -RRB- -LSB- 7 -RSB- . With the emergence of 40 and 64-slice MDCT systems the assessment of lumen visibility and diagnostic accuracy of in-stent restenosis has been improved considerably with respect to the 16-slice MDCT systems -LSB- 8 , 9 -RSB- . The artificial lumen narrowing shows a decrease of approximately 5 % and the CT attenuation is reduced by approximately 35 HU -LSB- 10 -RSB- . Visualisation of the in-stent lumen with 16-slice MDCT allows for the assessment of coronary artery stent patency based on the measured enhancement of contrast -LSB- 11 -RSB- . It has been shown that the best diagnostic quality images are obtained with a sharp edge-enhancing reconstruction kernel , although the quality of the obtained images is hampered by increased noise levels compared with standard kernels -LSB- 11 -- 13 -RSB- . The results originate from the comparison of the lumen visibility images pairs , which are reconstructed with different reconstruction kernels . The apparent lumen width is measured using a digital measuring tool included in the visualisation software . This method , however , is subjective to the observer and it is difficult to determine the exact boundary of the stents in the gradient part of the image . In addition , the image quality of the stents is very sensitive to the movement of the heart and image quality diminishes at heart rates higher than 75 beats per min -LRB- bpm -RRB- -LSB- 14 , 15 -RSB- . In previous studies , a patient population was used to investigate image quality of coronary artery stents at high and low heart rates on four - and 16-slice MDCT -LSB- 14 , 15 -RSB- . To our knowledge no systematic study has been published about the image quality of coronary artery stents on 64-slice MDCT . In this study , we therefore aimed at describing the correlation of image quality of coronary artery stents and heart rate using 64-slice MDCT in an ex-vivo setting by using an anthropomorphic moving heart phantom . The purpose of our study was to assess the lumen visibility of coronary artery stents at various heart rates with an automated objective method using a moving heart phantom on a 64-MDCT system . Theory Coronary imaging is hampered by motion artefacts originating from the relative large velocity scale of the coronary arteries within the cardiac cycle compared with the temporal resolution of the MDCT acquisition technique -LSB- 16 -RSB- . This movement results in motion artefacts in the reconstructed images , expressed as blurring . The amount of blurring depends on -LRB- 1 -RRB- the amount of movement of the imaging target MS and -LRB- 2 -RRB- the acquisition time -LRB- AT -RRB- . The amount of movement of the coronary artery is a function of the heart rate -LRB- HR -RRB- of the patient . The temporal resolution of a MDCT system is a function of the reconstruction method used and HR -LSB- 17 , 18 -RSB- . This means that the resulting image quality -LRB- IS -RRB- can be expressed as in which MS describes the amount of movement of the coronary artery as a function of heart rate , AT describes the acquisition time as a function of heart rate and g is a weight factor . The heart rates can be ranked from low to high . With this ranking , a relative grading can be made for the function MS. In addition , the acquisition times can be ranked from high to low . With this ranking , a relative grading can be made for the function AT . The results of this grading are shown in Electronic supplementary material -LRB- ESM -RRB- Table 1 , where a high score implies a high image quality . Since there is no cardiac movement at 0 bpm , this heart rate was graded with the highest score for both factors . Materials and methods Nine commercially available stents were used and stent dimensions were measured using a digital calliper . The stent properties are summarised in ESM Table 2 . The stents were inserted into plastic tubes and the tubes were filled with contrast fluid -LRB- Visipaque 320 , Amersham Health , Little Chalfont , UK -RRB- diluted to an attenuation value of approximately 200 HU simulating contrast enhanced blood . The tubes were wrapped in horse fat with an attenuation value of − 100 HU to simulate the in vivo situation of epicardial fat -LRB- Fig. 1left -RRB- . Fig. 1Left : schematic figure showing the experimental setup of the contrast fluid filled tube surrounded by horse fat in the axial plane . The numbers depict the HU values of the different relevant structures . Right : moving anthropomorphic heart phantom with artificial coronary arteries Next , the stents were attached to a silicon , moving , anthropomorphic heart phantom -LRB- Limbs & Things , Bristol , UK -RRB- with artificial coronary arteries -LRB- Elastrat , Geneva , Switzerland -RRB- -LRB- Fig. 1right -RRB- . The phantom is connected to a respirator , which was used to control the heart rate . The heart rate was set at values of 0 , 50 , 60 , 70 , 80 , 90 and 100 bpm . Measurements have been performed on a 64-detector CT-scanner -LRB- Somatom Sensation 64 , Siemens , Forchheim , Germany -RRB- . The scan parameters were 120 kV , 120 mAs , 370 ms rotation time and 64 × 0.6 mm collimation . Image reconstruction was performed using a sharp convolution kernel -LRB- Siemens B46f -RRB- with a reconstruction slice width of 0.75 mm and a 0.5-mm increment . ECG-gating was used during scanning and the images were retrospectively reconstructed at 25 % of the RR-interval corresponding to maximum expansion of the heart phantom . Afterwards the stents were visualised on an Aquarius workstation version 3.3 -LRB- Terarecon , San Mateo , USA -RRB- . We used two independent methods to asses the lumen visibility of the stents in the reconstructed images . In the first method , the average HU-value in the stent lumen was manually measured with a standard region of interest -LRB- ROI -RRB- technique . A window level/width of 300/800 was used for visualisation with an average ROI of 5.0 mm2 and 3.9 mm2 in the longitudinal and axial plane , respectively -LRB- Fig. 2 -RRB- . The lumen measurements were used to calculate the mean CT attenuation in the stent lumen . In the second automated method , screenshots were taken from every stent in the longitudinal and the axial plane with a window level/width of 512/2 ,048 . The screenshots were used to perform the automated lumen visibility measurements using a dedicated tool . Fig. 2Measuring the CT attenuation in the lumen . Left : measurements in the axial plane , Lekton Motion at 60 bpm . Right : measurements in the longitudinal plane , Lekton2 at 90 bpm . Calculated by the Aquarius workstation are mean HU-value , standard deviation and area of ROI The automated lumen visibility measurements were performed with an Automatic Stent Visibility Calculation -LRB- ASVC -RRB- , a custom-build Matlab tool -LRB- The Mathworks , Natick , USA -RRB- . The tool constructs the average attenuation profile through the stent in the longitudinal and axial plane . The calculation of the average attenuation profile in the longitudinal plane is done as follows ; attenuation profiles are calculated from position A to B for every image line perpendicular to the stent central axis , where the position A and B are determined by the user -LRB- Fig. 3left -RRB- . The average longitudinal profile is calculated from the individual longitudinal profiles . The calculation of the average attenuation profile in the axial plane is doen as follows : after determination of the centre of the stent by the user , 180 attenuation profiles are calculated evenly distributed around the centre -LRB- Fig. 3right -RRB- . The average axial attenuation profile is calculated from the individual axial profiles . Fig. 3Stent images -LRB- left : Jostent Stent Graft at 60 bpm ; right : Taxus at 80 bpm -RRB- showing the positions of the individual profiles for calculation of the average stent profile in the longitudinal plane -LRB- left -RRB- and the axial plane -LRB- right -RRB- The profile depth of the lumen -LRB- D -RRB- , the full width at half maximum -LRB- FWHM -RRB- and the total width -LRB- TW -RRB- are calculated from both average profiles -LRB- ESM Fig. 4 -RRB- . We define the percentual width -LRB- Wp -RRB- as a percentage of the FWHM and TW The percentual width is used instead of the absolute width to compensate for different magnifications of the stent images . From the profile depth -LRB- D -RRB- and Wp , the lumen visibility -LRB- LV -RRB- is defined by If the left and right edge of the attenuation profile are at different heights , D is calculated from the average height . The stent images at individual heart rates were ranked according to their CT attenuation -LRB- 7 = least attenuation , 1 = most attenuation -RRB- , FWHM -LRB- 7 = largest width , 1 = smallest width -RRB- and D -LRB- 7 = largest depth , 1 = smallest depth -RRB- in the axial and longitudinal plane . The difference between the CT attenuation values in the axial and longitudinal plane were compared using the Wilcoxon test at a significance level of 5 % . The correlation between heart rate and CT attenuation , and the correlation between heart rate and LV , were analysed by calculating the Spearman rank correlation coefficient at the significance level of 5 % . Results CT attenuation in the stent lumen The results for the HU-value measurements are summarised in ESM Tables 3 and 4 for the longitudinal and axial plane , respectively . The CT attenuation in the stent lumen was calculated for each heart rate and the results are shown for the longitudinal and axial plane in ESM Figs. 5 and 6 , respectively . The error margins have been omitted to improve readability of both figures . All stents showed increased attenuation with increasing heart rate in the longitudinal plane . The CT attenuation in the longitudinal plane showed an increase from 0 to 100 bpm between 75 and 221 HU for the Taxus and Bx Sonic stent , respectively . The average increase was 139 ± 49 HU . The average Spearman coefficient for all stents was 0.66 . All stents showed increased attenuation with increasing heart rates in the axial plane . The CT attenuation in the axial plane showed an increase from 0 to 100 bpm between 76 and 252 HU for the Bx Sonic , Multi-link Zeta and the Jostent , respectively . The average increase was 148 ± 69 HU from 0 to 100 bpm . The average Spearman coefficient in the axial plane was 0.58 . The average increase of CT attenuation over both planes was 144 ± 59 HU . Using the ASVC , the FWHM and depth of the stent profile were determined . The results for the FWHM are summarised in ESM Tables 5 and 6 ; the results for the profile depth are summarised in ESM Tables 7 and 8 . The standard deviation for every measurement is given in parentheses . The LV was calculated using equations 2 and 3 at each HR using the measured width FWHM and depth D . The data are plotted in ESM Figs. 7 and 8 for the longitudinal and axial plane , respectively , and have been fitted to a line . Error margins have been omitted to improve readability . All stents showed decreasing LV with increasing heart rate in the longitudinal plane . The LV decreased from 0 to 100 bpm between 7.5 % and 48.6 % for the Taxus and Cypher stent respectively . The average decrease in LV was 26.8 ± 13.4 % . The average Spearman coefficient was 0.47 . All stents showed decreasing LV with increasing heart rates in the axial plane . The LV decreased from 0 to 100 bpm between 19.8 % and 48.8 % for the Lekton and Multi-link Zeta stent respectively . The average decrease in LV was 30.9 ± 10.4 % . The average Spearman coefficient was 0.58 . The average decrease of LV over both planes was 29 ± 12 % . Image scoring The measurements are shown in ESM Fig. 9 after grading and averaging as described in the methods section . From a least squares fit , we found an optimal value of g = 0.63 ± 0.06 . Discussion Coronary artery stenting is a successful method to treat stenosis . However , re-stenosis in the stent may happen after the procedure . This makes check-ups a necessary procedure to perform -LSB- 19 , 20 -RSB- . MDCT is one the candidates for visualisation of the lumen of coronary artery stents . Although the results look promising , the image quality is hampered by cardiac movement and metal artefacts -LSB- 21 , 22 -RSB- . This may result in blurred images and an exaggerated thickness of the stent struts compromising the visibility of the lumen . The 64-MDCT scanner has increased spatial and temporal resolution compared with previous CT scanner generations -LSB- 23 , 24 -RSB- and increased LV of coronary stents is expected with these new scanners . Although 64-MDCT imaging of coronary artery stents show an improved image quality with respect to previous CT scanners , the images still show blooming artefacts and blurring -LSB- 9 -RSB- . The apparent width is measured in a generally accepted method to assess the stent lumen , but this method is very subjective to the user -LSB- 25 -RSB- . In contrast , our method , developed in this study to analyse the stent lumen , is an automated method . It enables the possibility of a systemic evaluation of the stent lumen at various heart rates . The in vivo conditions were approached as much as possible using contrast fluid and fat . Influence of increasing heart rate To our knowledge there have been no previous studies systematically investigating the relation between heart rate and image quality of coronary stents using 64-MDCT . There are , however , some studies with 16-slice MDCT assessing coronary arteries , which concluded that for successful cardiac imaging a heart rate below 75 or 70 bpm is necessary -LSB- 14 , 15 , 26 -- 29 -RSB- . In a study with 40-MDCT by Gaspar et al. -LSB- 8 -RSB- , patients were given an oral beta-blocker if their heart rate was higher than 65 bpm , and in a study with 64-MDCT , patients were given beta-blockers if their heart rate was higher then 70 bpm -LSB- 30 -RSB- . Ferencik et al. -LSB- 23 , 30 -RSB- concluded that a low heart rate is an important prerequisite for excellent image quality . ASVC Two different methods were used to assess the relationship between heart rate and image quality of coronary stents . The first method , the CT attenuation measurement , is a commonly used method . The second method , the ASVC technique , is a new approach . Both methods show a negative correlation between image quality and heart rate as expressed by the linear fits . The fits , however , show small significance . This small significance can be explained by the fact that the image quality does not depend entirely on heart rate , which shows a linear behaviour , but also on temporal resolution , which shows a non-linear behaviour , as can be seen from ESM Fig. 9 . Despite the poor quality of the fit , the results obtained with this new ASVC method are in agreement with previous studies using generally accepted methods as stated before . Therefore , we conclude that our developed tool is a valid method for the analysis of coronary stent lumen . Image scoring The image scoring results -LRB- Fig. 9 -RRB- show a varying resemblance between the theoretical scoring and the measured scoring . This resemblance depends on the proportion g and varies between 0 -LRB- IS completely depends on AT -RRB- and 1 -LRB- IS completely depends on MS -RRB- . The best resemblance was found for g = 0.63 . This implies that the cardiac movement causes almost twice as much blurring in the CT image compared with blurring caused by the limited temporal resolution of the acquisition method . Multi-segment reconstruction -LRB- MSR -RRB- has been developed to further increase the temporal resolution -LSB- 6 , 18 , 32 -RSB- . The data acquisition at a rotation time of 370 ms and a HR > 65 bpm has been performed during two consecutive heart cycles using a two-segment MSR . At heart rates of 70 and 90 bpm , the data acquisition is approximately evenly distributed over two consecutive heart cycles . At 80 and 100 bpm , however , the majority of data is acquired in the first heart cycle , and the remaining portion in the second heart cycle . From Fig. 9 , we can deduce that for HR of 70 and 90 bpm the measured IS is smaller than the theoretical IS . For HR of 80 and 100 bpm , the measured IS is larger than the measured IS . From this we can conclude that it is beneficial to the image quality to acquire during one cycle and that the MSR technique is not beneficial to image quality . In contrast to this , Halliburton et al. -LSB- 31 -RSB- showed that MSR is beneficial for 16-slice MDCT . Two other studies concluded that MSR was not beneficial to the image quality for four-slice MDCT , in accordance with our results -LSB- 31 , 32 -RSB- . This can be explained by the fact that the coronary artery has to be in exactly the same position in the two heart cycles for the MSR algorithm to work properly . However , in general the starting position of the arteries at the beginning of the heart cycle will not exactly be the same as in the previous heart cycle . This phenomenon will introduce additional motion artefacts which result in extra blurring to the image , as has been shown before by Greuter et al. -LSB- 33 -RSB- . Reducing blurring Cardiac movement and limited temporal resolution will introduce blurring in CT images of coronary arteries . The result for image scoring showed that the influence of cardiac movement is almost twice as large as the influence of the temporal resolution . To reduce blurring , it is therefore more efficient to reduce the heart rate than to increase the temporal resolution . Limitations These results have been obtained using a moving heart phantom . It remains uncertain how well these results are applicable to patients . However , a previous study showed that the movement of the heart phantom is a good approximation to the in-vivo situation -LSB- 18 -RSB- . Furthermore , in order to approach the in-vivo situation as close as possible , contrast fluid and fat were used , with CT attenuation values equal to those in-vivo . Screenshots captured with the visualisation software were used to perform LV measurements . A loss of information is expected due to image compression used in the . jpg format of the screenshots . However , a comparison between the screenshot method and direct analysis using dicom files showed no observable difference in results . Conclusion We have shown that at increasing heart rates the CT attenuation in the stent increases and the lumen visibility decreases . A new approach to asses the stent lumen has been described which shows similar results to CT attenuation measurements and previous studies . The cardiac movement during data acquisition causes approximately twice as much blurring compared with the influence of temporal resolution . We conclude that a lowering of the heart rate is more beneficial to image quality than using a multi-sector reconstruction technique . In addition , we conclude that it is beneficial to image quality to acquire data in one cardiac cycle . Electronic Supplementary Material Below is the link to the electronic supplentary material . Fig. 4 Figure showinf the profile of the Bx Sonic at 80 bpm with the different variables which are determined by the ASVC ; the dotted blue line depicts the error margins of the profile . TW total width ; D depth ; FWHM = full width half minimum -LRB- DOC 56 kb -RRB- Fig. 5 CT attenuation measured in the stent lumen at various heart rates in the longitudinal plane -LRB- DOC 76 kb -RRB- Fig. 6 CT attenuation measured in the stent lumen at various heart rates in the axial plane -LRB- DOC 77 kb -RRB- Fig. 7 Lumen visibility plotted versus heart rate in the longitudinal plane -LRB- DOC 75 kb -RRB- Fig. 8 Lumen visibility plotted versus heart rate in the axial plane -LRB- DOC 74 kb -RRB- Fig. 9 The measured IS -LRB- green -RRB- , the theoretical IS for g = 0.63 -LRB- blue -RRB- , the theoretical IS for g = 0 -LRB- dotted red -RRB- , the theoretical IS for g = 1 -LRB- dotted orange -RRB- -LRB- DOC 53 kb -RRB- Table 1 Acquisition times for a 64-MDCT with 370 ms rotation time , number of cycles used and theoretical scores for every HR used in this study . AT acquisition time ; MS the amount of movement of the imaging target -LRB- DOC 32 kb -RRB- Table 2 Commercial name , manufacturer , material , length and diameter of the stents used in the study -LRB- DOC 33 kb -RRB- Table 3 HU-value measurements in the longitudinal plane -LRB- DOC 34 kb -RRB- Table 4 HU-value measurements in the axial plane -LRB- DOC 34 kb -RRB- Table 5 Results of the measured FWHM in the longitudinal plane -LRB- DOC 34 kb -RRB- Table 6 Results of the measured FWHM in the axial plane -LRB- DOC 34 kb -RRB- Table 7 Results of the measured profile depth in the longitudinal plane -LRB- DOC 34 kb -RRB- Table 8 Results of the measured profile depth the axial plane -LRB- DOC 34 kb -RRB-

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Mycoplasma hominis deep wound infection after neuromuscular scoliosis surgery : the use of real-time polymerase chain reaction -LRB- PCR -RRB- Mycoplasma hominis is a commensal of the genitourinary tract . It mostly causes infections to associated structures of this system ; however , occasionally it is a pathogen in nongenitourinary tract infections . Since , M. hominis strains require special growth conditions and can not be Gram stained , they may be missed or delay diagnosis . This report describes a deep wound infection caused by M. hominis after neuromuscular scoliosis surgery ; M. hominis was recovered by real-time polymerase chain reaction -LRB- PCR -RRB- . An awareness of the role of M. hominis as an extragenital pathogen in musculoskeletal infections , especially in neuromuscular scoliosis , being a high-risk group for postoperative wound infection , it is necessary to identify this pathogen . Real-time PCR for postoperative deep wound infection , in patients with a history of genitourinary infections , decreases the delay in diagnosis and treatment . In these cases rapid real-time PCR on deep cultures should be considered . Introduction Deep wound infections complicating spinal surgery are sources of major morbidity in neuromuscular scoliotic patients . Enterobacter , Enterococcus , Escherichia coli , Proteus and Staphylococci account for the majority of postoperative spinal wound infections in these patients -LSB- 28 -RSB- . Increasingly , previously uncommon pathogens are being identified in surgical infections . These organisms may be difficult to identify and/or resistant to most of the broad-spectrum antibiotics used for preoperative prophylaxis and for the treatment of postoperative wound infections . Among these pathogens , Mycoplasma hominis has been recognized as a cause of postoperative wound infections -LSB- 25 , 27 , 31 -RSB- . M. hominis is a commensal bacterium in humans and is distinguished phenotypically from other bacteria by the minute size and lack of a cell wall . As a result , M. hominis can not be Gram stained and is resistant to penicillin and other antibiotics that interfere with the cell wall metabolism . In addition , it is a fastidious slow-growing organism , which may not be readily identified by using routine culture protocols . Early diagnosis , however , is of utmost importance for adequate institution of appropriate antimicrobial therapy . To our knowledge , only two cases of postoperative spinal wound infections due to M. hominis have previously been reported -LSB- 18 -RSB- . We describe a case report of a M. hominis postoperative deep wound infection in a patient with a progressive myelomeningocele scoliosis who underwent posterior scoliosis surgery with bone allograft . Real-time polymerase chain reaction -LRB- PCR -RRB- provided a fast and secure diagnosis , which prevented further complications . Case presentation An 11-year-old girl with a complete paraplegia at level L2 -- L3 caused by a myelomeningocele was admitted to our hospital for surgical correction of a progressive right convex scoliosis . Preoperative physical examination revealed a flexible right convex thoracic scoliosis with a left convex thoracolumbar curve . The unsupported sitting anteroposterior radiograph showed a right convex thoracic scoliosis of 55 ° and a left convex thoracolumbar curve of 42 ° with no pelvic obliquity . Her medical history revealed a shunted hydrocephalus with an Arnold Chiari type II malformation , chronic urinary tract infections , and an auto-augmentation of the bladder . The patient was treated with single stage scoliosis correction involving posterior instrumentation -LRB- Xia ™ spinal system , Stryker Spine , Cestas , France -RRB- from T3 to L5 . The spondylodesis was completed by applying allograft bone chips -LRB- Netherlands Bone Bank Foundation , Leiden , The Netherlands -RRB- over the laminae in the thoracolumbar region . In addition , Collagraft ® -LRB- Neucoll , Campbell , CA , USA -RRB- , a synthetic bone graft substitute composed of collagen and a composite mineral -LRB- hydroxyapatite and tricalcium phosphate -RRB- , was applied posterolateral in the lumbosacral region . Prophylactic antibiotics , cefazolin -LRB- cefalosporin , Kefzol ® -RRB- 1,000 mg IV , were administered at the induction of anaesthesia , and as a second and third dose 8 and 16 h postoperatively , respectively -LSB- 6 -RSB- . Because of a chronic urinary tract infection including a positive culture with E. coli , cefradin -LRB- cefalosporin , Velosef ® -RRB- 500 mg orally was continued for 9 days at 8-h intervals . The postoperative course was uneventful . At day 8 the patient was discharged . At discharge the wound produced negligible clear fluid at the distal end without any signs of infection . However , at day 18 postoperatively , the patient developed fever -LRB- 39 °C -RRB- and was readmitted to our centre . On physical examination , an enlarged distal wound dehiscence was seen with increased fluid production . Infection parameters showed an increased C-reactive protein -LRB- CRP -RRB- -LRB- 120 mg/l ; normal < 10 mg/l -RRB- and white blood cell -LRB- WBC -RRB- count -LRB- 10.9 cells × 109/l ; normal 4 -- 10 cells × 109/l -RRB- . A surgical intervention was performed including a thorough debridement of necrotic tissue and removal of the bone grafts . The instrumentation was left in place . According to the established guidelines , cultures were taken of various deep areas by fluid aspiration and from the applied bone graft -LSB- 15 , 28 , 32 -RSB- . After extensively irrigating with pulsatile lavage , the wound was closed leaving gentamicin collagen fleeces -LRB- Septocoll ® , Biomed , Darmstadt , Germany -RRB- over the instrumentation . Adjuvant therapy with gentamicin -LRB- aminoglycoside , Garamycinl ® -RRB- 210 mg IV and flucloxacillin -LRB- isoxazolylpenicillin , Floxapen ® -RRB- 2,000 mg IV were initiated immediately after obtaining appropriate intraoperative cultures , and was continued postoperatively at 6-h intervals . Intraoperative cultures from both the fluid aspiration and the bone graft yielded Mycoplasma after 4 days incubation . Real-time PCR on the peri-operative biopsy material was only positive for Mycoplasma and the species was identified by 16S DNA amplification as M. hominis -LRB- Fig. 1 -RRB- . Separately a Collagraft ® sample of the same batch was tested for Mycoplasma , however , the culture as well as real-time PCR remained negative . Gentamicin and flucloxacillin were stopped , and doxycycline -LRB- tetracycline , Vibra-S ® -RRB- 100 mg was administered orally at 12-h intervals and continued for 3 weeks . The patient was discharged 5 days after surgery . Fig. 1Agarose gel analysis of duplo PCR amplification of Mycoplasma DNA . M Molecular weight marker , Lanes 1 and 2 positive PCR amplification of clinical sample , lane 3 negative control , lane 4 positive control . Subsequent sequencing results revealed M. hominis Wound healing and temperature were monitored at regular intervals at the outpatient clinic . After 3 months , the infection parameters were normalized and the wound was healed -LRB- Fig. 2 -RRB- . Four years after surgery there were no signs of infection . Radiographs at final follow-up demonstrated no instrumentation failure and no loss of correction of the scoliotic deformity -LRB- Fig. 3 -RRB- . Fig. 2Clinical appearance 3 months after surgical intervention for deep wound infection , located at the distal end of the woundFig . 3AP radiographs of the lumbar spine at the site of the deep wound infection immediately after surgical intervention and debridement of necrotic tissue including removal of the bone grafts -LRB- a -RRB- and at 4 years of follow-up -LRB- b -RRB- Discussion Mycoplasma hominis is a commensal bacterium in humans . The organism is commonly associated with infections of the genitourinary tract , particularly in females . Rates of colonization in the urogenital tract range from 21 to 54 % among women and from 4 to 13 % among men -LSB- 20 -RSB- . Reports on M. hominis infections outside the genitourinary tract are scarce . Most of them are case reports describing extragenital infections , such as septic arthritis -LSB- 17 , 21 -RSB- , septicemia -LSB- 11 , 12 -RSB- , prosthetic valve endocarditis -LSB- 3 , 10 -RSB- , postoperative wound infections -LSB- 25 , 31 -RSB- , peritonitis -LSB- 13 -RSB- , neonatal encephalitis -LSB- 30 -RSB- , meningitis -LSB- 7 , 9 -RSB- , brain abscess -LSB- 33 -RSB- , thrombophlebitis -LSB- 27 -RSB- , and mediastinitis -LSB- 19 -RSB- . Extragenital infections are mainly related to patients with immunosuppression -LSB- 3 , 7 , 9 , 17 , 19 , 21 , 25 , 27 , 30 , 33 -RSB- . Osteomyelitis caused by M. hominis is predominantly reported in combination with hypogammaglobulinemia -LSB- 5 , 14 , 16 , 24 -RSB- . In an extensive overview of nongenitourinary M. hominis infections , Madoff and Hooper -LSB- 18 -RSB- described only two cases of postoperative deep wound infections caused by M. hominis after orthopedic surgery . Both cases concerned with deep wound infections after scoliosis surgery , one of them with a history of pyelonefritis . Postoperative deep wound infections after scoliosis surgery are more common in neuromuscular patients than in patients with idiopathic scoliosis -LSB- 28 -RSB- . Risk factors associated with increased postoperative wound infection rates include a generalized decline in the immune status of neuromuscular patients , poor personal hygiene , and soiling of the wound . Sponseller et al. -LSB- 28 -RSB- reported 25 patients -LRB- 12 % -RRB- with a deep wound infection out of a series of 210 surgically treated patients with neuromuscular scoliosis in a 10-year retrospective study . From these 25 patients , 16 had a scoliosis related to myelomeningocele . Two risk factors were found to be significant : the degree of cognitive impairment and use of bone allograft . Furthermore , 52 % of the infections were polymicrobial , which could point to contamination during or after surgery . However , the authors did not report any case of M. hominis wound infections in their series . Antibiotics are used routinely to prevent postoperative wound infection in patients undergoing spinal implant procedures . Currently , first or second-generation cephalosporin -LRB- e.g. cefazolin -RRB- are recommended as prophylaxis -LSB- 6 -RSB- . Prophylactic cefazolin was also routinely given in our case . Since , cephalosporins act on the cell wall of organisms in a manner similar to the penicillins , postoperative wound infection by M. hominis was not prevented . Antimicrobial treatment for M. hominis include protein-synthesis inhibitors such as tetracycline -LRB- e.g. doxycycline -RRB- -LSB- 26 -RSB- and doxycycline was administered accordingly . The postoperative deep wound infection resolved favorably after surgical debridement and appropriate antimicrobial treatment with doxycycline . The source of M. hominis deep wound infection in our case is unclear . M. hominis is commonly associated with infections of the genitourinary tract -LSB- 20 -RSB- and patients with meningomyelocele are known to have a high incidence of urinary tract infections -LSB- 8 -RSB- . In addition , it has been shown that children with myelomeningocele have a high incidence of urological complications after surgical treatment of scoliosis -LSB- 4 -RSB- . Possibly , in our case the M. hominis could have been present in the urinary tract infection and spread hematogenous or by contamination , either at the time of surgery or secondarily through the wound . Other possible sources are the materials that were used during surgery . Obviously , the instrumentation and the applied Collagraft ® , were sterilized . In addition , cultures and PCR on the same batch of the Collagraft ® were negative . Bone allograft , used to induce and facilitate spinal fusion , could also have been the source of the infection . The fact that the bone allograft was positive for M. hominis , proved that it was infected before retrieval , however , not that it was the source of the infection itself . Bone allograft has not been reported as a carrier of M. hominis in the literature , however , it must be noted that the standard screening at the Netherlands Bone Bank Foundation does not include screening on M. hominis . Unfortunately , no other specimen of the donor could be retrieved for testing . As a result , haematogenous spread or contamination from a colonized urogenital tract or contamination by the bone allograft as source of the infection could not be excluded . In the presented case , cultures taken during the reintervention proved to be positive for Mycoplasma . However , the diagnosis of a Mycoplasma infection was delayed due to the fastidious nature of mycoplasmas . To identify the Mycoplasma species , which in our case was cultured , 16S DNA amplification was used . Because isolation of M. hominis is difficult , time consuming , and not routinely done , a rapid specimen processing is required . Real-time PCR on deep cultures could provide a rapid alternative with a higher sensitivity and specificity than culture for the detection of M. hominis -LSB- 1 , 2 -RSB- . In conclusion , M. hominis infections should be considered in postoperative deep wound infection after neuromuscular spinal surgery , especially in patients with genitourinary tract comorbidity . Since , M. hominis is not covered by routine prophylactic and therapeutic antibiotics , rapid real-time PCR is advised in these patients to initiate appropriate antibiotic treatment .

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mycoplasma hominis
wound infection
neuromuscular scoliosis
pcr


Successful outcome of six-level cervicothoracic corpectomy and circumferential reconstruction : case report and review of literature on multilevel cervicothoracic corpectomy The authors report the successful outcome of a six-level corpectomy across the cervico-thoracic spine with circumferential reconstruction in a patient with extensive osteomyelitis of the cervical and upper thoracic spine . To the authors ' knowledge , this is the first report of a corpectomy extending across six levels of the cervico-thoracic spine . Clinical relevance : the authors recommend anterior cage and plate-assisted reconstruction and additional posterior instrumentation using modern spinal surgical techniques and implants . Introduction Multi -LRB- two or more -RRB- - level disease of the anterior cervical and upper thoracic spine can occur from degenerative , traumatic , infectious , and neoplastic causes . Successful treatment is dependent upon adequate decompression , immediate spinal reconstruction , and ultimately , the achievement of bony fusion . Decompression of the anterior cervical spinal canal can be achieved either by anterior cervical discectomy and fusion -LRB- ACDF -RRB- or anterior corpectomy and fusion -LRB- ACF -RRB- . Across multiple levels , ACF offers several advantages over ACDF , including wider decompression and more complete removal of pathology causing spinal cord compression , and fewer graft-host interfaces that must consolidate for successful bony fusion . Corpectomies of the cervical and cervico-thoracic spine have been reported to extend across as many as four levels -LSB- 5 , 15 , 16 -RSB- . More extensive corpectomies have not been reported perhaps because of concerns for instrumentation failure and expected difficulty in obtaining adequate exposure of the anterior cervicothoracic spine . We present a successful six-level cervicothoracic corpectomy and circumferential reconstruction in a patient with vertebral osteomyelitis and epidural abscess . Case report History and presentation A 50-year-old HIV-positive woman with a history of alcohol and drug abuse presented to our institution with a 7-month history of progressive neck pain , dysphagia , and radiculomyelopathy . Her past medical history was also significant for hepatitis B and multiple episodes of alcohol-induced acute pancreatitis . She denied a history of opportunistic infections . She had not been compliant with anti-retroviral therapy . Physical examination On physical examination , the patient was unable to extend her neck above the horizon and demonstrated 4 + out of 5 motor strength throughout all muscle groups . Preoperative halo traction was not applied as the patient reported an intolerable amount of pain with any manipulation of her cervical spine . Imaging studies Plain radiographs and computed tomography -LRB- CT -RRB- imaging demonstrated extensive bony destruction and a marked kyphotic angulation of the cervicothoracic spine -LRB- Fig. 1 -RRB- . Magnetic resonance imaging revealed extensive prevertebral and epidural enhancement surrounding the cervical and upper thoracic spinal cord resulting in circumferential narrowing of the thecal sac -LRB- Fig. 2 -RRB- . These findings were consistent with the diagnosis of vertebral osteomyelitis/discitis and epidural abscess . Fig. 1 -LRB- Left -RRB- Swimmer 's view radiograph demonstrating kyphosis related to C4 -- T2 osteomyelitis . -LRB- Right -RRB- Sagittal reformatted CT scan demonstrating extensive osseous erosion with kyphotic angulation from C6 -- T2 . Note that the apex of the kyphotic deformity is at the junction of the cervical and thoracic spineFig . 2 -LRB- Left -RRB- Sagittal T1 post-gadolinium MR sequence revealing extensive prevertebral and circumferential enhancing epidural abscess and enhancing vertebrae , compatible with osteomyelitis . -LRB- Right -RRB- Sagittal T2-weighted MR image demonstrating abnormal T2 signal within the spinal cord at the T1 -- 2 level -LRB- arrow -RRB- Operation An anterior approach to the cervical spine was performed first . The patient was positioned supine with traction on a halo ring in extension to partially reduce the kyphotic deformity . Next , a longitudinal incision along the medial border of the right sternocleidomastoid muscle was made and connected to a median sternotomy which was performed for exposure of the T1 -- T3 vertebral bodies . Wide exposure of the C3 -- T3 vertebral bodies was then carried out . Leksell rongeurs were used to remove the C4 , C5 , C6 , C7 , T1 and T2 vertebral bodies down to the posterior longitudinal ligament . Next , an appropriately-sized lordotic titanium cage -LRB- Pyramesh ; Medtronic Sofamor Danek , Memphis , TN , USA -RRB- was packed with iliac crest autograft and recombinant human bone morphogenic protein -LRB- rhBMP -RRB- and impacted into position . A slotted dynamic Aesculap ABC plate -LRB- Aesculap AG , Tutlingen , Germany , and Aesculap Instrument Corp. , South San Francisco , CA , USA -RRB- was then affixed to the spine with variable-angle screws into the C3 and T3 bodies . Next , the patient was turned prone and the halo head holder secured to a Mayfield frame . The posterior spine was dissected out from C1 -- T5 and Stealth image guidance -LRB- Medtronic Sofamor Danek , Memphis , TN , USA -RRB- was then used to place pedicle screws bilaterally at C2 and from T1 -- T4 . Next , lateral mass screws were placed bilaterally at C3 and C4 and on the left side at C5 . A laminectomy was performed from C4 -- T2 . Tapered rods were then attached to the lateral mass and pedicle screws and secured bilaterally . Thorough decortication of the facet joints from C2 -- T4 was performed . Additional rhBMP and autograft was packed into the decorticated facets and lateral gutters . A lateral radiograph was obtained before closure to confirm satisfactory graft and hardware placement . After removal from the Mayfield frame , the halo brace and vest were then secured on the patient . Total blood loss was 2,000 cc and the total operating time was 8 h. Postoperative course Postoperative AP and lateral plain radiographs showed good hardware positioning with correction of the kyphotic deformity -LRB- Fig. 3 -RRB- . The patient was kept in the halo brace postoperatively . She began ambulating with physical therapy on postoperative day -LRB- POD -RRB- # 3 . She experienced improvement in her neurological symptoms during the hospitalization . Due to the extensive dissection of her anterior cervical spine , a feeding tube was placed in the immediate postoperative period and was removed on POD # 15 . She was discharged to home on POD # 30 in good condition to complete a 6-week course of intravenous antibiotics for Staphylococcus aureus osteomyelitis . Fig. 3Postoperative AP and lateral radiographs after six-level corpectomy from C4 -- T2 , anterior interbody contoured cage and anterior plating from C3 -- T3 . Posterior screw-rod fusion is evident from C2 -- T4 . Note that the T1 pedicle screws have been shortened to avoid breeching into the cage anteriorly Follow-up At 4-month follow-up , the patient 's neurological exam was improved from presentation and she demonstrated full strength throughout all muscle groups , normal sensation and resolution of neck pain . She was able to ambulate without assistance and denied any problems with breathing or swallowing . Plain flexion-extension radiographs of the cervico-thoracic spine were obtained after the patient was removed from the Halo vest -LRB- Fig. 4 -RRB- . At last follow-up -LRB- 2.5 years -RRB- , the patient continued to remain neurologically intact without neck pain and no evidence of hardware failure . Fig. 4Flexion -LRB- left -RRB- and extension -LRB- right -RRB- plain radiographs obtained at 4-month follow-up demonstrate good hardware positioning without graft dislodgment . Note that the significant correction of sagittal plane alignment is maintained . There is no motion of the instrumented spinal levels Discussion Anterior corpectomy and fusion is perhaps the most effective procedure for wide spinal cord decompression in patients with severe canal stenosis or pathology of the anterior spine -LSB- 16 -RSB- . Compared to more conventional surgical techniques for spinal cord decompression , such as ACDF , laminectomy , and laminoplasty , patients treated with ACF have better neurological recovery , less axial neck pain , and lower incidences of postoperative loss of sagittal plane alignment -LSB- 21 , 24 , 25 -RSB- . Extensive ACF involving three or more levels ; however , involves more complicated surgical exposure and has been associated with increased rates of graft-related complications , including graft dislodgment , spinal cord compression , and pseudoarthrosis -LSB- 12 , 19 , 20 , 22 -RSB- . That the anterior graft is subject to significant compressive forces after extensive ACF has been confirmed in biomechanical studies -LSB- 8 , 23 -RSB- . Although each surgeon must take into account the clinical indications , risks and benefits of ACF in every patient , it seems logical to assert that the reported experience with ACF has been limited to four or fewer levels out of concern for these potential complications . Reconstruction after extensive ACF , therefore , is critical to prevent graft failure and allow for successful bony fusion . Anterior column reconstruction after extensive ACF may be performed using strut grafts or titanium mesh cages . Allo - or auto-graft struts may subside into the adjacent vertebral bodies or dislodge and cause cord compression -LSB- 6 , 12 , 26 -RSB- . Titanium mesh cages offer several advantages over strut grafts , including better correction of sagittal alignment -LRB- with pre-contoured cages -RRB- , better endplate purchase , variable height and diameter options , and the ability to be packed with auto - or allograft bone -LSB- 4 , 7 , 13 -RSB- . Indeed , we were able to achieve significant correction of sagittal alignment in our patient with the use of a lordotic titanium cage . The addition of anterior plate fixation after interbody grafting enhances the rigidity and stability of the construct and therefore lowers the risk of graft-related complications -LSB- 3 , 5 , 9 , 16 , 20 -RSB- . Supplemental posterolateral fixation after extensive ACF has been found to further decrease the rates of graft-related complications , deformity correction loss , and pseudoarthrosis rates -LSB- 8 , 10 , 16 , 18 , 20 , 23 -RSB- . Nevertheless , even with posterolateral fixation , in our experience there is inevitably a certain amount of subsidence of the anterior graft after extensive ACF . We used a slotted dynamic plate that allows for changes in the angle and alignment of the vertebral body screws to accommodate this expected subsidence -LRB- Fig. 4 -RRB- . Other options to prevent subsidence-related failure of the anterior plate include using a cage only -LRB- no plate -RRB- , buttress plates , or creating flanges in the cage that overlap the adjacent vertebral bodies and are secured with non-constraining screws -LSB- 1 -RSB- . It is important to note ; however , that we did not perform postoperative CT to demonstrate bridging trabecular bone and therefore can not definitively conclude that successfully bony fusion occurred in our patient . Nevertheless , we believe the absence of hardware motion on flexion-extension plain radiographs at 4-month follow-up does demonstrate the stability of this patient 's extensive construct . Our patient has subsequently been lost to follow-up and it must be recognized that a pseudoarthrosis may manifest only after several years with a slowly progressive kyphosis . Finally , both in vitro and in vivo studies have shown that BMP and rhBMP can promote bony fusion and arthrodesis -LSB- 2 , 11 , 14 , 17 , 27 -RSB- . While fusion-promoting agents such as rhBMP are expensive and their use in the cervicothoracic spine is ` off-label , we believe it may improve the likelihood of fusion after the very extensive bone removal and instrumentation during this procedure and their use is therefore justified . Conclusions A six-level corpectomy across the cervico-thoracic spine can be safely performed by combining a traditional longitudinal exposure of the cervical spine with a median sternotomy . Circumferential reconstruction with modern implants , such as an anterior contoured titanium cage-dynamic plate construct and posterior screw-rod fixation , is necessary to provide sufficient stability of the cervico-thoracic spine to allow for correction of sagittal alignment and to achieve bony fusion . While the lack of a CT scan demonstrating bridging trabecular bone precludes a conclusion that radiographic fusion occurred in our patient , we believe that the absence of new or worsening clinical symptoms at 2.5-year follow-up demonstrates the long-term stability and potential for successful fusion of this reconstruction . Fusion-promoting agents may be used to increase the fusion rate of these kinds of constructs with substantial bone loss and use of extensive instrumentation systems .

O O O O O B O O B O O O O O O O O O O B O O O O O O O O O B O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O B O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B I O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O

corpectomy
cervical spine
fusion
reconstruction


Erythropoietic protoporphyria without skin symptoms-you do not always see what they feel Erythropoietic protoporphyria -LRB- EPP -RRB- is an inherited disorder of the porphyrin metabolism that often remains undiagnosed in children . We report on a 4-year-old girl who had been suffering for 1 year from recurrent painful crises affecting her hands , feet , and nose following sun exposure . Objective skin lesions were absent until the age of 6 . Porphyrin analysis revealed elevated free erythrocyte protoporphyrin -LRB- FEP -RRB- levels confirming the diagnosis of EPP . This illustrates that skin lesions might be completely absent in children affected with EPP , a fact that has only been reported once previously . Because EPP can manifest with few and unspecific cutaneous symptoms or no skin lesions at all , like in this patient , the diagnosis of EPP might be delayed or missed . EPP should be excluded in all photosensitive children , especially when discomfort is disproportionate to the extent of the cutaneous lesions . The clinic , pathophysiology , diagnosis , complications , and therapy of EPP are discussed . Introduction Erythropoietic protoporphyria -LRB- EPP -RRB- -LRB- OMIM 177000 -RRB- results from a partial deficiency of ferrochelatase -LRB- FECH -RRB- , the last enzyme in heme biosynthesis that is located in the mitochondrium -LSB- 10 , 13 -RSB- . FECH catalyzes the insertion of iron into protoporphyrin IX to form heme -LRB- Fig. 1 -RRB- -LSB- 10 -RSB- . Although overall EPP is a rare disease , it is the most common type of porphyria manifesting in childhood with an estimated prevalence of 1 in 130,000 -LSB- 10 , 13 , 23 -RSB- . Fig. 1In the mitochondrium , ferrochelatase catalyzes the formation of heme from protoporphyrin IX . ALA : δ-aminolevulinic acid The disease has no racial or sex predilection and no precipitating factors have been described to date -LSB- 10 , 20 -RSB- . The major clinical feature of EPP is cutaneous photosensitivity that usually commences early in infancy or childhood , affects the sun-exposed body sites , and worsens in spring and summer -LSB- 10 -RSB- . The symptoms include pain , burning , itching , erythema , and swelling , which can develop within minutes of sun exposure -LSB- 4 , 10 , 13 , 14 -RSB- . Petechiae , purpura , and vesicles may be seen , but are uncommon -LSB- 4 -RSB- . Typically , children experience relief when cooling the skin with cold water or wet towels -LSB- 11 -RSB- . Chronic UV -LRB- ultraviolet -RRB- exposure can lead to lichenification , postinflammatory hyperpigmentation , and scarring , particularly over the knuckles and on the nose -LSB- 13 , 23 -RSB- . Of note , the cutaneous symptoms can be discrete and barely notable in early childhood despite significant subjective discomfort including burning and stinging sensations in the skin . Here , we describe a girl with EPP with an unusual clinical course , demonstrating that parents and physicians can not always recognize how much the patients suffer . Case report An otherwise healthy , 4-year-old Dutch Caucasian girl presented with a 1-year history of suddenly occurring severe itching and pain in the hands , feet , and nose after sunlight exposure . These sensations lasted up to 3 days , and she reported on three such incidents during the last 12 months . The symptoms developed either immediately or up to 8 h after UV exposure . Erythema or other skin manifestations were not seen . The condition worsened in the summer months and during vacations in sunny climates . Itching commenced immediately after sunlight exposure and reached a maximum at night . After a few hours , the itching changed into pain . Application of wet towels or cold baths led to partial relief , and the symptoms usually vanished spontaneously after a couple of cloudy days without intense UV exposure . Looking back , her parents also remembered that at the age of 1 year , during a summer vacation , she had suffered from an unexplained acute swelling of the hands and feet . At that time no specific diagnosis was made , besides the suspicion of an allergy . During that vacation at the sea side , the overall family life was disturbed because she was continuously agitated , cried a lot without an apparent reason , and did not sleep well . Upon physical examination in our outpatient clinic at the age of 4 , she showed no skin symptoms except for few minimal excoriations on the dorsal aspects of the feet . The family history revealed eczema in the mother and atopy in the paternal grandmother , but was unremarkable regarding increased photosensitivity . Eventually , a pediatrician suggested the differential diagnoses polymorphic light eruption , warmth intolerance , or hypochondria , and the girl was treated unsuccessfully with antihistamines . Due to continuation of her complaints , a pediatric dermatologist was consulted who suspected EPP despite the absence of cutaneous manifestations . Blood porphyrin analysis revealed elevated free erythrocyte protoporphyrin -LRB- FEP -RRB- levels of 9,821 μg/l -LRB- normal 0 -- 300 μg/l -RRB- , confirming the diagnosis of EPP . Affirmative phototesting showed maximal cutaneous sensitivity at a wavelength of 400 nm -LRB- violet light -RRB- . Full blood count and liver enzymes were normal . Therapeutically , strict UV light avoidance , protective sunscreens , and annual follow-up visits were advised . Still , her photosensitivity did not improve , and mild hyperpigmentation and sores at her nose and upper lip as well as pronounced knuckles and progressive lichenification developed at the age of 6 . To date , she has not shown liver enzyme alterations . Discussion Here we present a girl with EPP who suffered from a significant decrease of quality of life due to severe itching and pain of the skin . Clinically , EPP is characterized by cutaneous photosensitivity manifesting early in life . Acute photosensitivity episodes include burning , stinging , and pruritus in sun-exposed skin , particularly on the nose , cheeks , and dorsal aspects of the hands , followed by erythema , edema , and wax-like scarring . Skin symptoms can occur within minutes of sun exposure , often starting early in spring time , continuing through the summer , and diminishing in fall and winter . Interestingly though , our patient did not show any visible skin lesions until the age of 6 . Over the last 30 years there have been ten reports on children with EPP who developed mild to severe cutaneous photosensitivity and specific skin manifestations -LSB- 1 , 2 , 11 , 15 , 19 -- 21 , 23 , 30 , 31 -RSB- . With mild or absent visible skin symptoms , however , diagnosis may be delayed for several years or is not made at all because the discomfort experienced by the young patients is disproportionate to the objective cutaneous manifestations -LSB- 22 , 23 -RSB- . Thus , children with EPP are often labeled as hysterical , hypochondriac , or even malingering , a distressing situation for both the patients and their parents -LSB- 2 , 22 -RSB- . To the best of our knowledge the complete absence of visible skin lesions in early childhood EPP has only been described once to date -LSB- 12 -RSB- . The symptoms in EPP are associated with an overproduction and accumulation of lipophilic protoporphyrin as a result of FECH deficiency -LSB- 28 -RSB- . Excess deposition of protoporphyrin in the skin leads to cutaneous photosensitivity upon UV light exposure with maximum susceptibility at a wavelength around 400 nm -LRB- Soret band -RRB- -LSB- 22 -RSB- . Upon excitation , protoporphyrin exerts its phototoxic effects through the generation of reactive oxygen species -LRB- ROS -RRB- . ROS can induce lipid peroxidation , oxidation of amino acids , and mediator release from mast cells , contributing to the acute photosensitivity , and protein cross-linking leading to cell membrane damage and cell death -LSB- 3 , 7 , 13 , 17 , 25 -RSB- . The diagnosis of EPP is based on the clinical symptoms and verified by a significant increase of FEP -LRB- more than five times the normal level of 0 to 300 μg/l -RRB- in peripheral erythrocytes -LSB- 15 , 18 , 28 -RSB- . Since protoporphyrin is a hydrophobic metabolite , it is not renally excreted . Hence , urinary porphyrin values are usually normal -LSB- 15 , 23 -RSB- . Another diagnostic modality includes fluorescence microscopy of erythrocytes -LSB- 2 , 17 -RSB- . Histological changes are predominantly seen in the upper dermis and include deposition of amorphous material containing immunoglobulins , complement components , glycoproteins , acid glycosaminoglycans , and lipids around blood vessels -LSB- 5 , 21 , 24 , 26 , 27 , 29 -RSB- . However , these alterations are not specific . Regardless of the aforementioned finding , we emphasize that it is unnecessary to take a skin biopsy if one of the cutaneous porphyrias is suspected because of two reasons . Firstly , simple non-invasive biochemical laboratory techniques can easily prove or exclude the presumptive diagnosis of porphyria . Secondly , any kind of external trauma , such as a biopsy or excision , inevitably constitutes an unnecessary risk for delayed or disturbed wound healing in porphyria patients . The differential diagnoses of EPP include solar dermatitis , solar urticaria , polymorphous light eruption , lipoid proteinosis , hydroa vacciniforme , and lupus erythematosus -LSB- 2 , 22 -RSB- . Elevated FEP levels can also be found in lead poisoning , anemia , renal failure , cholestasis , and liver failure . However , these conditions are not associated with photosensitivity -LSB- 13 , 18 , 23 -RSB- . Beside the cutaneous manifestations , the most important concern in EPP patients is the development of cholestasis with rapid accumulation of protoporphyrin in hepatobiliary structures resulting in severe liver damage and hepatic failure . Although rarely occurring , progressive liver failure is a well-recognized complication in EPP , and about one third of EPP patients show biochemical liver abnormalities -LSB- 6 , 13 -RSB- . Therefore , liver function tests should be performed annually -LSB- 13 , 28 -RSB- . In our patient , no liver dysfunction has been detected so far . Although in rare instances an autosomal recessive inheritance pattern has been described , EPP is a predominantly autosomal dominantly transmitted disorder with incomplete penetrance resulting from mutations in the FECH gene on chromosome 18q21 .3 -LSB- 31 , 32 -RSB- . To date , more than 65 different FECH mutations have been reported , reflecting the genetic heterogeneity encountered in EPP -LSB- 13 , 28 -RSB- . Recently , the genetic mechanisms underlying the cutaneous symptoms in EPP have been uncovered . It is clear now that only those individuals will develop skin symptoms who not only inherit a heterozygous FECH gene mutation on one parental allele , but also a specific intronic FECH polymorphism on the other parental allele -LSB- 8 -RSB- . Thus , clinically overt EPP results from a marked deficiency of FECH activity below a certain threshold due to co-inheritance of a specific FECH gene mutation with a low-penetrance IVS3-48C allele . Recent studies indicate that the frequency of the IVS3-48C allele shows a high degree of variability in different ethnic groups -LSB- 9 -RSB- . The identification of the molecular mechanisms underlying the manifestation of photosensitivity in EPP certainly has to be considered a milestone in porphyria research . Still , the development of protoporphyrin-induced hepatic disease and the molecular mechanisms governing the phenotype with severe liver injury are not well understood . It seems that other as yet unidentified factors may contribute to the pathogenesis of severe liver failure in EPP . The current treatment modalities for EPP are limited and not effective in all patients -LSB- 13 -RSB- . In an ideal scenario , the harmful effects of exposure to visible light should be prevented . This can partially be achieved with sunscreens containing titanium oxide or zinc oxide . Common sunscreens , even those with high UV absorption capacity , do not block visible light and , thus , have no protective effect -LSB- 2 , 28 -RSB- . Consequent avoidance of UV light exposure and sun protection by protective clothing remains the most important measure in preventing acute photosensitivity and was also advised to our patient -LSB- 13 , 14 , 18 , 28 -RSB- . The effectiveness of other modalities such as antioxidants -LRB- e.g. , beta-carotene -RRB- , cysteine , narrow-band UVB-phototherapy , and oral antihistamines remains doubtful and is certainly not of benefit in all patients . In the future , gene therapy approaches might play a role in the treatment of EPP because , e.g. , normal ferrochelatase activity could be restored in vitro by transferring a wild-type copy of the FECH gene into cultured fibroblasts of EPP patients -LSB- 16 -RSB- . In conclusion , the diagnosis of EPP is often delayed or missed . Therefore , EPP should always be considered in photosensitive children , especially when the subjective discomfort is disproportionate to the extent of visible skin manifestations because we obviously do not always see what these patients feel . If cutaneous symptoms are completely absent , an accurate diagnosis is difficult and requires all diagnostic abilities of the attending physicians .

B I O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

porphyrias
erythropoietic protoporphyria
ferrochelatase
photosensitivity