Thursday, January 9, 2020


BILATERAL MORGAGNI HERNIA IN A CASE OF WEILL – MARCHESANI SYNDROME- A RARE ASSOCIATION
Abstract
Morgagni hernia constitutes only about 2% of all diaphragmatic hernias and bilateral morgagni hernia is extremely rare. Here we present a 75 year old female patient with morphometric features of Weill-Marchesani syndrome who has bilateral morgagni hernia. This association is reported for the first time in literature.
Introduction
Weill-Marchesani syndrome is due to connective tissue abnormality and is inherited as autosomal dominant or recessive disorder. Clinical features of this syndrome include Short stature, Stiffness of joints of upper limbs, microspherophakia, ectopia lentis, low set flat palate and other bony abnormalities. This is considered as the opposite of Marfan’s syndrome. Since connective tissue is defective in this condition weakness of fibro-muscular structures like diaphragm may be expected. Morgagni hernia occurs through the anteriolateral foramen of diaphragm and is mostly seen on the right side. Bilateral morgagni hernia is extremely rare. It is proposed that weakness of the diaphragmatic muscle fibres may be the cause for this rare presentation in Weill Marchesani syndrome.
Case Report
A 75 year old female patient presented to the Pulmonary Medicine Outpatient department. She was referred by her treating physician as a case of right lower lobe pneumonia. She is a diabetic and hypertensive for the last 8 years and was well controlled on medication. She used to work as a head load worker in a coffee plantation and was leading a retired life at present. She was never a smoker but used to chew tobacco. She had six live births and gives history of  history of four term babies dying in utero. 
On examination she is of short stature and poorly nourished.  There is exaggerated thoracic kyphosis and scoliosis to the leftt. Chest movements are diminished on right lower part with impaired percussion note. Breath sound was diminished on right side and coarse crackles were heard on right lower part.
A presumptive diagnosis of right lower lobe pneumonia with sympneumonic effusion was made. Blood routine and sputum examinations were within normal limits. Her symptoms responded to antibiotic and symptomatic measures. The follow up X-Ray showed a nonhomogenous opacity right lower zone. CT thorax revealed that the shadow is due to herniation of abdominal contents to thorax. It demonstrated bilateral Morgagni hernia. There is omentum and transverse colon herniating through right foramen and omentum herniating through left foramen with a definite cleavage separating the two.
This case is unique in that it demonstrates the association of two rare clinical entities. To our knowledge, this is the first report of a bilateral Morgagni hernia in a patient with Weill Marchisani syndrome.
Discussion
Weill-Marchesani syndrome is a disorder of connective tissue. As connective tissue forms the body's supportive framework, providing structure and strength to the muscles, joints, organs, and skin, this syndrome has unique abnormalities in different organ systems. The major signs and symptoms of Weill-Marchesani syndrome include short stature, eye abnormalities, unusually short fingers and toes (brachydactyly), and joint stiffness especially in upper limbs. The eye abnormalities include small, sphere-shaped lens (microspherophakia) and ectopia lentis. These patients may later develop glaucoma, leading to blindness. Occasionally, heart defects or an abnormal heart rhythm can occur in people with Weill-Marchesani syndrome.
Weill-Marchesani syndrome (WMS) appears to be rare with an estimated prevalence of 1 in 100,000 people. WMS can be inherited as an autosomal recessive or an autosomal dominant pattern. Mutations in the ADAMTS10 and FBN1 genes can cause WMS syndrome. The ADAMTS10 gene provides instructions for making a protein which is important for normal growth before and after birth, and it appears to be involved in the development of the eyes, heart, and skeleton. Mutations in this gene disrupt the normal development of these structures, which leads to the specific features of WMS. The FBN1 gene provides instructions for making a protein called fibrillin-1. This protein is needed to form micro fibrils that provide strength and flexibility to connective tissue. The FBN1 mutation responsible for WMS leads to an unstable version of fibrillin-1. This unstable protein interferes with the normal assembly of micro fibrils, which weakens connective tissue and causes the abnormalities associated with WMS. This can affect all fibromuscular structures including diaphragm.
Congenital Morgagni Hernia (CMH) is a rare constituting roughly 2% of all congenital diaphragmatic hernias (CDH)1. Herniation abdominal content occurs through anterolateral or triangular parasternal gaps in the diaphragm2. This mostly occurs on the right side, though they can rarely occur on the left or bilaterally 3. They are generally asymptomatic and incidentally found during an unrelated diagnostic workup 4. Berman et al 5 treated only 18 cases of CMH over a period of 40 years and Pokorny et al 6 reported only 4 cases of CMH over a period of 25 years. Cigdem et al treated 16 cases of CMH over a period of 23 years 7.
Giovanni Battista Morgagni, an Italian anatomist, first described the herniation of abdominal contents through the sternochondral triangles in 1769 based on cadaver observation 8. Later, in 1828, Larrey described a surgical approach to the pericardial sac through these same triangles. The costochondral triangles have been referred to as the foramen of Morgagni on the right and the space of Larrey on the left. They form when the pars sternalis and a costochondral arch fuse and close around the internal thoracic artery as it becomes the superior epigastric artery. Occasionally these spaces do not fully close and allow for the herniation of abdominal contents into the thorax2, 9.
Morgagni hernias can be diagnosed during any period of life including prenatal period 10.The majority of these hernias, 90%, occur on the right side of the sternum while the remaining 8% are present on the left 11. Bilateral Morgagni hernia only makes up 2% of all Morgagni hernias. The hernias most frequently contain omental fat and transverse colon. They rarely contain liver or stomach 12. Sometimes herniation occurs into the pericardial cavity. When this occurs, serious cardiorespiratory compromise may result13, 14. In adults Morgagni hernia is also associated with obesity, trauma, weight lifting, or other causes of increased intra-abdominal pressure. Our patient was a head load worker and this can be a predisposing factor. In the pediatric age group, the presentation of CMH is variable and non-specific. Usually the presentation is that of recurrent chest infection and rarely may present with gastrointestinal symptoms. Our patient also reported with respiratory symptoms rather than gastrointestinal symptoms. Majority of patients suffered repeated attacks of chest infections received several courses of antibiotics and some of them were hospitalized several times.
There is an increased risk of associated anomalies with CMH, with a variable incidence ranging from 34% to 50% 3. One study reported as high as 78.3% associated anomalies in CMH4. This study also reported 34.8 % congenital heart disease with an overall 45.5 % of heart defects. ASD and VSD were the commonest associated heart defects. This however did not influence the final outcome and had no effect on the overall morbidity. An interesting association was that of CMH and Down’s syndrome. In a collective series of 46 children with Morgagni’s hernia, 16 (34.8%) of them had Down’s syndrome15. Cigden et al in a series of 16 patients with CMH seen over a period of 23 years reported a 31.25% incidence of Down’s syndrome 7. Other rare clinical associations of morgagni hernia are pulmonary hypoplasia, gastric volvulus, rotational abnormalities and midgut volvulus, hypoplasia of the left ventricle with a left-sided hernia or pleural effusions caused by right-sided involvement and bilateral renal hypertrophy.
Radiographic diagnosis of diaphragmatic hernias is typically made with chest radiographs, ultrasound (US), or computed tomography (CT). Chest radiography often requires anterior-posterior images to evaluate hernia severity and lateral images to evaluate hernia location. Images can vary depending on the contents of the hernia. Solid viscera protruding through the hernia may show an opaque hemithorax with or without mediastinal shift. Hollow viscera are often present as loops of bowel within the thorax. An anterior medial mass on chest radiography can be suggestive of a Morgagni hernia. Radiological differential diagnoses include pneumonia, atelectasis, diaphragmatic eventration, mediastinal lipoma, liposarcoma, abscess, and pleuropericardial cyst 16.
Computed tomography or ultrasound can be used to confirm a suspected diaphragmatic hernia. Multiphase CT can demonstrate the diaphragm and the organs that herniate through it. Omental vessels can be visualized in some diaphragmatic hernias and can help differentiate it from lipomas or liposarcomas. Intravenous contrast can help enhance these vessels and confirm a diagnosis 12.
Ultrasound is helpful in assessing diaphragmatic hernias that contain solid viscera. Hepatic echo-texture and color Doppler sonogram can confirm liver in thorax 17. Hernias that contain hollow viscera can be more difficult to evaluate with US. Air in the bowels and lungs, as well as rib shadowing, can often distort the images and make them difficult to interpret 12.
The association of Weill Marchesani syndrome and bilateral morgagni hernia is not previously reported in literature. Defective collagen in Weill Marchesani syndrome may be the cause for persistence of defect in the diaphragm leading to herniation. Thus causative relationship between the two clinical entities can be postulated. We propose that this is an extended syndrome of Weill Marchesani syndrome and would like to name it as Weill- Marchesani- Wayanad syndrome giving due credit to the place where it is first reported.
Conclusion
Weill- Marchesani syndrome is an inherited disorder in which there is defect in the collagen tissue. This can present with different manifestations in the body. Here we present a case of Weill- Marchesani syndrome with blateral Morgagni hernia and postulate that defective collagen may be the pathogenetic mechanism for persistence of foramen of Morgagni leading to herniation later. This association is being reported for the first time in literature.
References
1.      Torfs C. P., Curry C. J. R., Bateson T. F., Honore L. H. A population-based study of congenital diaphragmatic hernia. Teratology. 1992; 46(6):555–65.
2.      Sandstrom C. K., Stern E. J. Diaphragmatic hernias: a spectrum of radiographic appearances. Current Problems in Diagnostic Radiology. 2011; 40(3):95–115.
3.      Al-Salem A. H., Zamakhshary M., Al Mohaidly M., Al-Qahtani A., Abdulla M. R., Naga M. I. Congenital Morgagni's hernia: a national multicenter study. Journal of Pediatric Surgery. 2014; 49(4):503–507.
4.      Al-Salem A. H. Congenital hernia of Morgagni in infants and children. Journal of Pediatric Surgery. 2007; 42(9):1539–43.
5.      Berman L, Stringer DA, Ein SH, Shandling B: The late presenting pediatric Morgagni hernia: a benign condition. J Pediatr Surg 1989, 24: 970-72
6.      Pokorny WJ, McGill CW, Harberg FJ: Morgagni hernia during infancy: presentation and associated anomalies. J Pediatr Surg 1984, 19: 394-397
7.      Cigdem MK, Onen A, Okur H, Otcu S: Associated malformation in Morgagni hernia. Pediatr Surg Int 2007, 23:1101-1103
8.      Morgagni G. B. The Seats and Causes of Diseases Investigated by Anatomy; in Five Books, Containing a Great Variety of Dissections, with Remarks. New York, NY, USA: Hafner; 1960.
9.      Minneci P. C., Deans K. J., Kim P., Mathisen D. J. Foramen of Morgagni hernia: changes in diagnosis and treatment. Annals of Thoracic Surgery. 2004; 77(6):1956–59.
10.  Garne E., Haeusler M., Barisic I., Gjergja R., Stoll C., Clementi M. Congenital diaphragmatic hernia: evaluation of prenatal diagnosis in 20 european regions. Ultrasound in Obstetrics and Gynecology. 2002; 19(4):329–33.
11.  Nasr A., Fecteau A. Foramen of morgagni hernia: presentation and treatment. Thoracic Surgery Clinics. 2009; 19(4):463–68.  
12.  Eren S., Çiriş F. Diaphragmatic hernia: diagnostic approaches with review of the literature. European Journal of Radiology. 2005; 54(3):448–59.
13.  Pironi D, Palazzini G, Arcieri S, Candioli S, Manigrasso A, Panarese A, et al. Laparoscopic diagnosis and treatment of diaphragmatic Morgagni hernia. Case report and review of the literature. Ann Ital Chir. 2008; 79(1):29-36.
14.  Gucciardo L, Deprest J, Done' E, Van Mieghem T, Van de Velde M, Gratacos E, et al. Prediction of outcome in isolated congenital diaphragmatic hernia and its consequences for fetal therapy. Best Pract Res Clin Obstet Gynaecol. 2008; 22(1):123-38.
15.  Kubiak R, Platen C, Schmid E, et al: Delayed appearance of bilateral Morgagni’s hernia in a patient with Down’s syndrome. Pediatr Surg Int 1998,13: 600-601
16.  Anthes T. B., Thoongsuwan N., Karmy-Jones R. Morgagni hernia: CT findings. Current Problems in Diagnostic Radiology. 2003; 32(3):135–36.
17.  Taylor G. A., Atalabi O. M., Estroff J. A. Imaging of congenital diaphragmatic hernias. Pediatric Radiology. 2009; 39(1):1–16.



RESURGENCE OF TUBERCULOSIS DOTS FAILURE OR THOUGHT FAILURE!


RESURGENCE OF TUBERCULOSIS
DOTS FAILURE OR THOUGHT FAILURE!

The World Health Organization (WHO) declared tuberculosis (TB) a global public health emergency in 1993 and since then intensified its efforts to control the disease worldwide1. Revised National Tuberculosis Control Programme (RNTCP) and directly observed treatment short course (DOTS) were introduced in the country after a pilot study in 1997. The programme was introduced in a phased manner covering the whole population of the country by 2006.It enjoyed the back up of infrastructure of health care system, a new hierarchal human resource chain and huge external funding. The concept of daily, directly observed therapy, incorporating a full six months of Rifampicin has been adopted by the majority of countries worldwide as a major part of Stop TB Strategy2. Lower rates of cure in National TB Control program (NTP) highlight the operational challenges of delivering a daily regimen over an extended period of  time2, 3. India implemented the Revised National TB Control Program (RNTCP) as a national government run system that used a thrice weekly regimen administered by DOT4. Cure rates in India have been comparable with countries using daily dosing. TB mortality has dropped significantly, and the prevalence of TB has declined slightly over the last two decades4. The therapeutic regimens given under direct observation as recommended by WHO have been shown to be highly effective for both preventing and treating TB 5. It was propagated with much fanfare and enthusiasm and even the protagonists became ardent believers by the course of time. It took 30 years for the national tuberculosis control program to be declared a failure, but it took only 10 years or less to say that RNTCP is not achieving the desired result. Now the revised program is being re-revised citing examples of multidrug resistance and extensive drug resistance.
Directly observed therapy short course (DOTS) is the internationally recommended strategy to ensure cure of tuberculosis. It has become the standard for the diagnosis, treatment and monitoring of tuberculosis worldwide and has been implemented in 182 of 211 countries, covering more than 77% of world's population6,7 in response to the growing threat of this disease. 
In India, under the Revised National Tuberculosis Control Program (RNTCP), the percentage of smear-positive re-treatment cases out of all smear-positive cases is 24%8. The causes of re-treatment include relapse, failure, and default in treatment. RNTCP does not follow up the patients for any period of time after successful completion of treatment to determine whether they relapse. Due to the fact that India has the maximum number of cases and highest burden of TB in the world, an effective TB control program in India is essential. It also will have global implications in the international TB control effort. There is no statistically significant difference between the two treatment groups in terms of cure or treatment completion. Hill categorically admits that superiority of DOTS over unsupervised therapy for routine TB care has not yet been shown in an evidence-based fashion9. His contention is that it is not better in suboptimal settings and indicates that the program quality must be strong enough to yield its optimal benefits.  Of the new smear-positive patients registered under Category 1, the default and failure rates were 12% and 5%, respectively, reported by Chandrasekaran in 2006 and 16% and 4%, respectively, reported by Thomas10. Mehra recorded a failure rate of 3.4%11. The distribution of default and failure cases in Category 2 patients was 22% and 14%, respectively, in the study by Mukherjee12.  Hill in his review of studies from around the world, calculated an average failure rate to be 2.4% ±2.2% for 21 culture-based studies and 2.5% ±1.7% for nine smear-based studies9. Nevertheless, high relapse rate of 11-13% has been reported in patients treated by DOT under RNTCP from several different locations in India over the last many years 10, 13, 14.
Most authorities are convinced that DOTS improves treatment effectiveness, drug resistance rates, and overall TB control. It is a fact that the intermittent regimen used under the program is equally effective under direct observation as compared to the daily regimen, and choosing a daily regimen does not undermine the successes of the program 15, 16. There are no good quality studies that may cast light over the preferences, adherence, and felt problems of the clients of the RNTCP. Without understanding the wishes and the problems seen from the patients, it may be difficult to modify a strategy so strongly advocated by the WHO and many other international organizations working with TB. Role of HIV, Multi Drug Resistant (MDR) TB, re-infection with a different strain of Mycobacterium tuberculosis and outcomes in the pediatric age group, also need to be investigated for relapse. However, based on the above evidences and in the interest of having uniformity of care across all healthcare sectors it is decided to introduce daily regimen under RNTCP. It is argued that this will help to achieve universal access to quality TB care and prevent development of drug resistance. When such a decision is taken and program is being reintroduced, it will be better to take stock of what went wrong in the previous programs. It will help the program managers to take corrective steps so that the new program will not have the same fate after a few years.
The three main causes of failure of TB treatment relate to the actions of doctors in prescribing incorrect regimes, problems with the drugs being delivered (either the quantity or the quality), and the patients failing to take sufficient quantity of the drugs.
I.                   Doctors – Not adhering to guidelines or following inappropriate guidelines.
II.                Drugs –Poor quality, irregular supply and wrong delivery (dose/combination). In some case drugs are unsuitable due to the presence of drug resistance.
III.             Patients –Lack of information, Lack of money for treatment and/or transport, fear of actual or presumed side effects, lack of commitment to a long course of drugs and other co morbidity.
Apart from the above we have to consider few other reasons for the program failure. This is because system did not correct certain inherent causes of failure of the previous program (NTP).
1)      Administrative failure
The initial enthusiasm once the program was launched faded away too quickly. There was lack of commitment on the part of administrators. Most of the program managers and contractual staff were committed and RNTCP gained a lot of ground among common man due to their hard work. Most of the medical college faculty who were suspicious initially cooperated and it was bringing good result. This was mainly due to the concerted effort of program managers, District TB officers, medical college core committee members and contractual staff. But after few years these staff were shuffled and their grievances were never attended. Contractual staff on meager wages struggled to get that amount released in time. District program managers of NHM were responsible for dealing finances. Since they have many other programs to look after, due importance to TB program was never given. Once commitment is lost and enthusiastic workers left for greener pastures we can imagine the fate of the program.
Treatment adherence is a critical determinant of treatment outcomes. Poor outcome and emergence of drug resistance are mainly due to irregular and incomplete treatment. The DOTS strategy has been the backbone of TB programs for the last decade. In certain places, strict adherence to the program by healthcare worker has resulted in cost-effective and sustainable control of TB epidemics. However, accumulating evidence has pointed to the effectiveness of a wide variety of approaches including community and family-centered DOTS, which is more achievable for most developing healthcare systems and produce comparable outcomes to healthcare worker supervised DOTS.
However in a larger perspective, treatment support system developed with mutual trust and respect between the patient, family, providers, treatment supporters and the health system. This will promptly identify and address all possible factors that could lead to treatment interruptions. This includes not only medical factors such as co-morbidities, adverse drug reactions and emergencies, but also take care of various social, vocational, nutritional, economic and psychological stress experienced by the patient throughout the course of treatment. Regular and effective supervision by the health supervisors at various levels and close monitoring of the progress made by the patient on treatment are critical components to ensure high standards of care. Capacity building among health care workers and engaging local community based organizations, self-help groups and patient support groups could prove to be effective interventions to promote treatment adherence 17, 18. Supervision and support should be individualized and should include a range of recommended interventions including patient counseling and education. An important element of the patient centered strategy is to assess and promote adherence to the treatment regimen, and, to address poor adherence when it occurs. These measures should be tailored based on the patient's clinical and social history. It also should be mutually acceptable to the patient and the provider.

2)      Role of private practitioners
India continues to have high TB incidence, and, the mortality due to TB is still unacceptably high. The challenges of TB control in India are magnified by the existence of parallel systems for TB diagnosis and treatment – the public and the private. Each system takes care of approximately half of the TB cases19.The methods and standards vary greatly depending on whether public or private care is accessed and furthermore what type of private care is sought, from super-specialty tertiary institutions to non-qualified providers 20. RNTCP was implemented through the existing health care system, the pivotal role being played by district TB centers. There were additional staff supplement with adequate materials and funds. Every peripheral health center is empowered to take up the challenge of diagnosing, treating and monitoring TB patients. Since medical colleges are the opinion leaders in health care and trains new generation of doctors and paramedics there was an attempt to bring all medical colleges in the loop and hence task force is being organized in public and private medical education institutions. At the same time we are all aware that 50-60% of health care delivery in the country is through private practitioners. They work in institutions as well as individually. RNTCP, to a large extent, failed to bring these practitioners in to its fold. There were many concerns for them which were not addressed properly. Hence treatment of tuberculosis through private practitioners remained largely out of the program. Many institutions do not want to join a Govt. run program for fear of auditing. But most important of all is the fear of exposing their know how in treating tuberculosis. I know many practitioners using non rifampicin containing regimen, non-pyrazinamide containing regimen and levofloxacin based first line treatment. Many have more concern on liver dysfunction, peripheral neuropathy etc. and hence load the patient with two or more vitamins. This will all lead to non-compliance. Once therapeutic response is poor these patients are referred to the program. This previous treatment history is also poorly documented and may be a source of bias. It has been recorded that patients turn up at RNTCP after seeking medical care from many providers in the private sector. It might be true that many TB patients may see an advantage in not reporting previous treatment, in order to escape with a lighter 6-month treatment instead of a more punishing 8-month treatment regimen. When drug resistance is being reported from many parts of the country, these same practitioners started blaming the program.
3)      Availability of drugs in the open market
When the Govt. is committed to provide good quality anti TB drugs to patients in the country, why the drugs were made available in the open market? When these potent drugs are freely available, there is a chance to misuse these drugs to the extent of treating with inadequate regimen, inadequate dosing etc. This will lead on to failure and development of resistance. If it was banned when RNTCP was expanded to cover the whole nation, all the patients (suspected or diagnosed) will be brought to the single window of DOTS. This will ensure uniform treatment, treatment completion and follow up.
4)      Overemphasis on sputum microscopy and neglecting clinical and radiological evidence.
In NTP the main disadvantage being pointed out is overemphasis on radiology. X ray being highly sensitive but poorly specific, leads to more of false positives. When we turned to RNTCP the emphasis shifted to sputum microscopy. This is a highly specific test even though sensitivity is poor. So we have a proportion of false negatives in the society. Actually the planners should have developed a more realistic diagnostic test combining both. In the recent guidelines a new entity is included as clinically diagnosed TB which is diagnosed through clinical and radiological methods. Overdependence of sputum microscopy led to a peculiar situation in which clinicians failed to use their clinical judgment but blindly followed sputum microscopy result. Even after improvement in staining and detection, the sputum pick up remained as low as 60%. So 40% of TB cases roam around without being detected. When these patients are reported as negative after repeated sputum examination, there is hesitancy in starting anti-TB drugs. This leads to delay in starting treatment and progression of disease.
Conclusion
Urgent efforts are necessary for the control of tuberculosis in the country. Both intermittent and daily regimens are proved to be effective in treating tuberculosis. What is most essential is to ensure adherence to the program both from patient’s side and provider side. It is important to take stock of the factors leading to failure of previous programs and to take appropriate measures so that what is implemented now remains the standard of care for TB in years to come.

References
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16.  Wells AW et al. Implications of the current tuberculosis treatment landscape for future regimen change. Int J Tuberc Lung Dis. 2011; 15(6):746–53.
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19.  Satyanarayana S, Nair SA, Chadha SS, Shivashankar R, Sharma G, et al. () From Where Are Tuberculosis Patients Accessing Treatment in India? Results from a Cross-Sectional Community Based Survey of 30 Districts.PLoS ONE 2011; 6(9): e24160.
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