Treatment for Idiopathic Pulmonary Fibrosis

As everyone working in this field knows, the prognosis of idiopathic pulmonary fibrosis (IPF) is quite dismal (3 years survival of 50%). There have been many treatment regimens that have been suggested, but it is not clear whether any of them are of any use.

The latest issue of the New England Journal of Medicine (NEJM) has 3 articles and one editorial on this subject. The last one on acetyl-cysteine confirms that it does not really work.

However one more phase III trial by Talmadge King’s group on the use of pirfenidone, conducted because the US FDA was not convinced about its efficacy given the conflicting results from previous trials, shows that it does improve decline in lung function and overall survival.

The paper that however does bring a smile and some more hope is the first one by Richeldi Luca et al that shows the usefulness of nintedanib (where do come up with these names) in improving the reduction in FVC in patients with IPF.

There is a lovely short commentary / editorial that puts all these papers in perspective and even addresses the question of whether both nintedanib and pirfenidone should be used together and whether that would help even more or not. This is an interesting thought.

All of these are must reads for all those who have patients with IPF whose care they are responsible for.

 

Sub-centimeter Lung Nodule Biopsies

This article from the November issue of the American Journal of Roentgenology discusses the results of 305 CT guided core biopsies / aspirations of small lung nodules, less than 1.0 cm in diameter, over 13 years.

The only major variable that decided success was aspiration instead of core biopsy.

I have been very clear about doing core biopsies for lesions in the body as against FNAC / aspiration for many years now. Tissue today is needed for so much more than just establishing a diagnosis that if we are going to put a needle in the lungs, or other parts of the body, it would be a travesty to come away with only cells, without tissue.

Here is an example of a 7.5 mm lung nodule biopsied earlier this year that turned out to be tuberculosis on histopathology.

Biopsy of 7.5 mm lung nodule

Biopsy of 7.5 mm lung nodule

Managing a Pneumothorax – The Fear is Mostly in the Mind

Two weeks ago, in Beirut, I was speaking on the impact of modern imaging in pulmonary medicine, to a group of chest physicians from Egypt. The moment I started speaking on CT guided lung biopsies, a physician got up and started talking about the dreaded risk of pneumothorax. I have had similar reactions in other towns in India, including tier I cities like Delhi.

I explained to him that while a pneumothorax is not uncommon during CT guided biopsies, there are many ways to mitigate its seriousness; single puncture, minimal trauma, bleeding along the tract during withdrawal and arguably puncture side down for a few minutes are measures that reduce the severity and incidence of or prevent the occurrence of pneumothorax.

But even if a pneumothorax does occur, it is a slow event that takes its own time to increase, if it does. If a pneumothorax occurs during the procedure, it can be aspirated at the same time and more often than not, that cares of the problem and we can even continue with the procedure (Figure 1). In case the pneumothorax occurs after we have washed out as a delayed complication, then we can still aspirate it using an over the needle catheter. A recent video describing this procedure has been posted on The New England Journal of Medicine site. While this video shows the technique to be used in patients with spontaneous pneumothorax and describes a blind approach, we can use this simple procedure to aspirate under CT guidance as well and then check the status immediately on the CT scan table.

A and B show the start of a CT guided core biopsy of a subpleural nodule using a coaxial system. Since the nodule is immediately subpleural, the risk of pneumothorax is slightly higher than for a deeper nodule and C shows the developing pneumothorax. In D, the canula has been withdrawn into the pleural space and the pneumothorax was aspirated. E shows the biopsy continuing after the pneumothorax has been aspirated. It did not recur. Five minutes after the procedure, a scan in the supine position (G) shows a thin residual pneumothorax that was non-progressive.

A and B show the start of a CT guided core biopsy of a subpleural nodule using a coaxial system. Since the nodule is immediately subpleural, the risk of pneumothorax is slightly higher than for a deeper nodule and C shows the developing pneumothorax. In D, the canula has been withdrawn into the pleural space and the pneumothorax was aspirated. E shows the biopsy continuing after the pneumothorax has been aspirated. It did not recur. Five minutes after the procedure, a scan in the supine position (G) shows a thin residual pneumothorax that was non-progressive.

In the worst case scenario, an interventional radiologist should be able to put a tube in as well, despite the fact that the need to do this would be very low in experienced hands.

Persistence Pays with Hard Bones And Nuts

This story has been contributed by Dr. Argha Chatterjee, a third year PG in the department of Radiology at the Medical College and Hospital, Kolkata, after reading the earlier post on Tea and Fluorosis and in the spirit of this blog.

In his words…

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This is the story of a 28 year old gentleman, who presented to the general medicine out-patient department (OPD) with stiffness in both knees and spine for 2 years. He could not walk and was carried to the OPD by his neighbour. His knees were fixed at flexion and he had significant kyphosis. The doctors at the medicine OPD saw his knee radiographs done elsewhere, which showed gross osteopenia and a coarse trabecular pattern. The patient was admitted and radiographs of his knees, pelvis and lumbosacral spine were performed in our department.

A medicine post-graduate trainee (PGT) took away the “wet” films (it was a digital radiograph, so not really “wet”) and so it never came to us for reporting. After two days the radiographs were brought to our department by another medicine PGT. They were obviously confused because the pelvic and spine radiographs showed marked high bone density. They thought ofosteopetrosis but could not explain the osteopenia in the knees. They wanted to know what sclerosing bony dysplasia can cause both. In the meantime, the history had already taken a back seat.

What I saw was grossly increased bone density in the pelvis and lower lumbar spine associated with calcification and, at places, ossification at the ligamentous attachments (Figure 1). The knees showed osteoporosis, especially in the lower end of the femur (Figure 2). Calcification of the obturator membranes was present (Figure 3). There was coarsening of the trabeculae in all the visualised bones. Now, this is supposed to be a long case in the MD examination. So I said, “This is fluorosis.”

Frontal radiograph of the pelvis shows increased bone density and calcification at the ligamentous attachments (arrowheads).

Frontal radiograph of the pelvis shows increased bone density and calcification at the ligamentous attachments (arrowheads).

Frontal radiographs of both knees (fixed at flexion) show coarsening of the trabeculae and osteopenia at the lower ends of both femora.

Frontal radiographs of both knees (fixed at flexion) show coarsening of the trabeculae and osteopenia at the lower ends of both femora.

Oblique radiograph of the pelvis shows obturator membrane calcification (arrow).

Oblique radiograph of the pelvis shows obturator membrane calcification (arrow).

The PGT was not convinced. He argued for ostepetrosis. I countered that this was not dysplastic bone because the trabeculae were coarse; moreover the osteopenia and joint stiffness could not be explained by a dysplasia. He argued about the presence of coexistent osteopeia? I explained to him that osteoporosis is a known and important feature of skeletal fluorosis. In fluorosis, there is increased bone turnover. So initially there is high bone density (phase I) but later on, the long bones develop osteoporosis (phase II). He asked, “Isn’t there interosseous ligament calcification in fluorosis?” I pointed out the obturator membranes (Figure 3) and lesser trochanters. He said that his boss was not going to be convinced by just that. I agreed to arrange for a forearm radiograph free of cost.

The next morning I visited the patient’s bedside after reading up the clinical features of fluorosis. The patient had every feature. The stiffness started in the spine until he was finally immobile from knee stiffness. The PGT was there with a grin on his face. He said, “This is not fluorosis. The patient has no dental changes. I checked.”  I said that dental fluorosis occurs only when patient is exposed to high fluorine levels during the pre-eruptive stage of teeth. Then he dropped the bomb. “He is from Serampore, Hoogly!” Now this one floored me. The districts of West Bengal endemic for fluorosis are Purulia, Birbhum, Malda, Dinajpurs and South 24 PGs. Not Hoogly. I anyway asked for the forearm radiographs which were done later that evening. The forearm radiographs were classical for fluorosis (Figure 4).

Frontal radiographs of both forearm show classic interosseous membrane calcification (arrows).

Frontal radiographs of both forearm show classic interosseous membrane calcification (arrows).

Nevertheless the medicine unit did become serious about the diagnosis of fluorosis. A urine fluoride was done within the coming week but surprisingly it was normal. I thought my spot diagnosis was slipping away. About 2 weeks later, I met the same PGT in the canteen. I asked him about the case. He said a drinking water sample from the patient’s home was tested in a lab at Jadavpur University. The fluorine level was 2.5 mg/litre (WHO guideline value is less than 1.5 mg/litre). “The urine level?”, I asked. He told me that if a person is more than three weeks away from exposure, then the urine level may become normal. They finally diagnosed the case as skeletal fluorosis. He also told me that people at JU were surprised to find such high fluoride levels in Serampore.

I realised that day how important radiology can be in clinical diagnosis, sometimes against other evidence and we are, indeed, clinicians, not just image readers.

_________

For a comprehensive review of the radiology of skeletal fluorosis, please read this article.

Arghat’s contact: arghachat84 at gmail.com

Brittle Bones, Late Diagnosis

I received a call about 4 months ago from a family physician, who wanted me to perform a USG or CT guided biopsy for a mass in the anterior compartment of the right thigh in a 47-years old woman. He did not give me any more details and said the patient would get in touch with me.

I forgot about this, until a month later, when I was going through some histopathology reports of biopsies done by my ultrasonologist and chanced upon a report that described a hemangiopericytoma in the thigh with a comment saying that this was consistent with a phospaturic mesenchymal tumor.

Image

Fig. 1: Ultrasound shows the mass in the anterior compartment of the right thigh (red arrow) with the biopsy needle (blue arrow)

I called for more details and then realized that this was the same patient that the family physician, a month ago, had called about. Different people in our department do ultrasound and CT-guided biopsies and the patient went straight to the ultrasonologist, who in turn, went ahead and performed a core biopsy of the mass in the anterior compartment of the thigh (Fig. 1).

A phosphaturic mesenchymal tumor is a rare condition and typically secretes FGF-23 (fibroblastic growth factor) that produces osteomalacia. This combination is called oncogenic osteomalacia or tumor-induced osteomalacia (TIO).

I then asked the patient to get all the reports and details.

Image

Fig. 2: Radiograph shows an insufficiency fracture (arrow) of the base of the proximal right 3rd metatarsal bone.

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Fig. 3: Radiograph shows an insufficiency fracture (arrow) of the mid-left 5th metatarsal bone.

It had taken 5 years to get to this diagnosis. She started with an insufficiency fracture, five years ago, in the right 3rd metatarsal bone (Fig. 2), followed a month later by another fracture in the left 5th metatarsal bone (Fig. 3). She received symptomatic treatment and went from doctor to doctor with variable diagnoses of osteoporosis and perhaps osteomalacia.

This went on for 4 years, until one day, she was unable to get up from bed. She was admitted to a hospital and a skeletal survey showed fractures of the necks of both humeri (Fig. 5) and femurs (Fig. 6) with biconcave vertebrae (Fig. 7). Finally she received a diagnosis of osteomalacia and was worked up.

Her serum calcium was normal, vitamin D was normal, serum phosphorus was very low and her 24-hours urine phosphorus was elevated with a normal serum parathormone level and a raised serum alkaline phosphatase level. She did not fit into vitamin D related causes or phosphate deficiency conditions and what was left was a potential diagnosis of oncogenic osteomalacia.

Fig 4

Fig. 4: Radiographs of both shoulders show fractures (red arrows) of the necks of both humeri

Fig 5

Fig. 5: Radiograph of the bones of the pelvis and both hips show fractures (red arrows) of the necks of both femurs.

Lateral radiograph of the spine shows biconcave vertebrae

Fig. 6: Lateral radiograph of the spine shows biconcave vertebrae

Thus started the search for an FGF-secreting tumor that produces phosphaturia, hypophosphatemia and osteomalacia. A PET/CT then showed a mass with low FDG uptake in the anterior compartment of the thigh (Fig. 7), which was then biopsied. The common tumors that produce FGF are hemangiopericytoma, hemangioma, giant cell tumor and non-ossifying fibroma.

Contrast enhanced CT scan shows a hypervascular lesion (arrow) in the anterior compartment of right thigh, with mild FDG uptake (arrow) on the PET study.

Fig. 7: Contrast enhanced CT scan shows a hypervascular lesion (arrow) in the anterior compartment of right thigh, with mild FDG uptake (arrow) on the PET study.

She was operated and the tumor removed. Most patients show dramatic recovery of their phosphorus levels, but the skeletal changes and fractures take time to heal. The patient is slowly getting better symptomatically.

The most common reason for delayed diagnosis (in her case 5 years with an average time of 4.7 years from start of symptoms to final diagnosis) is due to lack of awareness and the inability to find the tumor.

This case was recently presented by our DNB resident Dr. Parang Sanghavi in the Teaching Files Case Presentation meeting in Mumbai, where it won the first prize in the 3rd year residents’ category.

Tea and Fluorosis

Tea and Fluorosis

Who would have thought that drinking tea can produced fluorosis. In keeping with the theme of this blog, this short story / report about a patient who developed fluorosis after drinking copious amounts of tea (yes, tea), everyday is extremely interesting.

How Fast is a Fast Response

This is a 29-years old lady who has a 4-months old child. A month after her pregnancy, she started getting some backache and chest pain and was feeling lethargic. She saw her family physician, who attributed all her symptoms and signs to post-pregnancy related issues and put her on standard symptomatic treatment, including vitamin D3 and B12 supplementation.

She did not improve and went to another family physician, who did not take her seriously as well and so she changed to a third family physician.

This last physician was concerned. She had been having fever and basic tests showed a raised ESR. According to him, she “did not look well”. He ordered a Mantoux and a CT scan of the chest both at the same time.

Her CT scan done on Mar 15, 2013, showed enlarged necrotic mediastinal nodes (Fig. 1), pericardial effusion and thickening (Figs. 1,2) and pleural effusions bilaterally (Figs. 2, 3).

Axial contrast-enhanced CT scan shows enlarged necrotic subcarinal and right hilar lymph nodes (red arrows) and pericardial effusion (blue arrow)

Axial contrast-enhanced CT scan shows enlarged necrotic subcarinal and right hilar lymph nodes (red arrows) and pericardial effusion (blue arrow)

Axial contrast-enhanced CT scan shows pericardial effusion (blue arrow) with thickening with left pleural effusion (white arrow)

Axial contrast-enhanced CT scan shows pericardial effusion (blue arrow) with thickening with left pleural effusion (white arrow)

Axial contrast-enhanced CT scan shows bilateral pleural effusions (white arrows)

Axial contrast-enhanced CT scan shows bilateral pleural effusions (white arrows)

She was asked to see a chest physician immediately. Her family came to see me and I advised the same.

In the mean time her Mantoux came strongly positive.

The chest physician started her immediately on first-line anti-tuberculous therapy with steroids for the pericardial effusion. Given the high incidence of primary multi-drug resistant tuberculosis in our country, he cautioned them that in case she did not improve clinically, she would need a CT guided subcarinal node biopsy and she was asked to see me again if that situation were to arise. There was no way to confirm the diagnosis at this time. The pleural fluid was too little and was unlikely to yield any results.

The next day, they called me and insisted on getting the biopsy done. Their reasoning was logical – they wanted to confirm the diagnosis and get material for culture and be sure that she was sensitive to first-line drugs. It is rare to find patients and families with such sensibilities.

I checked with the chest physician who agreed. If a patient wants a biopsy for confirmation, that is a request to be respected.

I posted her for a biopsy on 22 Mar, 2013. After standard counseling and explanations, I positioned her in the prone position to perform an extrapleural, CT guided subcarinal node biopsy. Lo and behold! The preliminary scans showed that the node had mildly regressed in size, the pleural effusions had regressed and the pericardial effusion had partly regressed.

I immediately called in the relatives and had the patient turn over and sit up. I explained to them that the partial regression meant response to treatment and that it made no sense to perform the biopsy at this point in time. They too agreed…they were so happy and relieved…these are the times when it is so gratifying to be a physician advising a patient. I repeated another contrast enhanced CT to document these findings (Figs. 4-6).

Axial contrast enhanced CT scans of 15 Mar and 22 Mar show partial regression of the subcarinal node.

Axial contrast enhanced CT scans of 15 Mar and 22 Mar show partial regression of the subcarinal node.

Axial contrast enhanced CT scans of 15 Mar and 22 Mar show partial regression of the pericardial effusion.

Axial contrast enhanced CT scans of 15 Mar and 22 Mar show partial regression of the pericardial effusion.

Axial contrast enhanced CT scans of 15 Mar and 22 Mar show complete regression of the pleural effusions.

Axial contrast enhanced CT scans of 15 Mar and 22 Mar show complete regression of the pleural effusions.

This is one of the fastest and quickest responses to tuberculosis that I have encountered.

Update 1:

A query on Facebook where I had posted this article asked whether there is an increased incidence of tuberculosis in the post-partum period. There is and this Pubmed link has the data.

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