Saturday, April 29, 2017

Pas Stain (Periodic acid–Schiff stain)

Pas stain or periodic acid-Schiff staining is a procedure used to visualize the presence of polysaccharides including glycogen and mucosubstances like glycolipids and glycoproteins.

It can be done alone or in combination with diastase. The procedure is called pas-d stain or pas diastase stain. Diastase is a type of enzyme responsible for breaking down glycogen. (1)

When is pas staining needed?

It is primarily intended for staining structures that contain a strong proportion of carbohydrate macromolecules, which is common in the mucus, connective tissues, basal laminae, and glycocalyx.

It is basically used to diagnose various medical conditions.

  1. Paget disease
  2. Glycogen storage disease
  3. Adenocarcinoma
  4. Staining the presence of macrophages in people with Whipple’s disease (a bacterial infection affecting the gastrointestinal system).
  5. Alveolar soft part sarcoma
  6. Diagnosing ╬▒1-antitrypsin deficiency in patients who turned out positive for periportal liver hepatocytes.
  7. Ewing sarcoma (a malignant tumor that is small, round and blue in color)
  8. Erythroleukemia (a type of leukemia involving the immature red blood cells)
  9. Glycogen storage disease. There is an excessive amount of glycogen in various parts of the company, particularly in the kidneys, liver, and muscles. Through pas staining, the accumulation of glycogen will be checked.
  10. The level of glycogen will be checked in patients with tumor, especially in the tissues of the lungs, bladder, and pancreas.
  11. Pas staining is used to visualize fungal organisms in the tissues of people with fungal infection.
  12. A pas stain is used to highlight the basement of the membranes of tissues. It is particularly helpful in diagnosing a glomerular disease in the kidneys. 
Image 1 : A good pas staining showing healthy parietal cells.
Photo Source : www.rcpaqapa.netcore.com

Figure 2 : A pas staining result characterized by blue color and a bit of violet discolorations.
Picture Source : drp8p5tqcb2p5.cloudfront.net

Photo 3 : In this image, there are blue, red, and purplish colors.
Image Source : www.epathologies.com

How pas staining done and what is are the processes involved?

There are various staining procedures, but the pas stain is one of the commonly performed staining procedures. It is important to have a knowledge about the procedure. Pas stain procedure is used to highlight the molecules with a high percentage of carbohydrates contents. How does it work? It works by exposing the tissues to a periodic acid. It will serve as oxidizing agent that oxidizes the vicinal glycol groups or the amino derivatives. The oxidation process creates dialdehydes that when exposed to Schiff’s reagent will turn out to an insoluble magenta compound. (1, 2)

What are the solutions used?

  • A 1% aqueous periodic acid
  • Schiff’s reagent

How it is done?

You have to take sections to water and expose it to periodic acid solution for about 10 minutes. Thoroughly rinse with tap water. After that, you have to expose the section to the Schiff’s reagent for approximately 15 minutes and wash with running tap water for about 10 minutes. It will be countestain with a haemtoxylin for about 15 seconds. When necessary, you have to differentiate the stain and dehydrate, clear, and mount. (3)

Pas stain color and its histologic feature

  • Magenta – it suggests the presence of glycogen, basement membranes, fungal organisms, and mucus substances.
  • Blue – Nuclei
  • Green with light green counterstain – Suggests other tissue elements (4)

Things to keep in mind when pas staining

  • There are available commercially prepared periodic acid and Schiff’s reagent.
  • It is important to keep the Schiff’s reagent away from the ultraviolet light. When not in use, make sure you refrigerate it. If you won’t do this, the sulphur dioxide content of the Schiff’s reagent will be lost. The solution will then change its color from colorless to magenta. If you notice this change, then you have to replace the solution. The periodic solution should be refrigerated too when not in use.
  • It is important to rinse the solution in running tap water to intensify the magenta color. Although the decision to rinse the solution varies from one lab to another. (5, 6)

What is GMS Staining?

Aside from pas staining, another method used is the GMS staining. It stands for Gomori-Grocott methenamine silver stain. It is particularly helpful in diagnosing onychomycosis or fungal infection of the nail. It is primarily used in cytology and histology to identify not just fungi but Pneumocystis jiroveci too. With GMS staining, the gram is placed in a hot bath for penetration. (5)

What is a reticulin stain?

The reticulin stain is one of the highly preferred methods in histology. It is done to visualize the reticular fiber and is. It is primarily used in liver histopathology particularly helpful in the FNAB cell block preparations, especially in the differential diagnosis of liver nodules and in distinguishing between HCC and benign hepatic processes.

A diagnosis of HCC is confirmed if the result of reticulin staining outlining trabeculae has more than three cells in thickness. On the other hand, a diagnosis of benign hepatic process is confirmed if the reticulin stain outlined a hepatic trabeculae that is less than three cell layers in thickness. (8)

What is a trichrome stain?

The trichrome stain or also known as connective tissue stain is used to histologically visualize collagenous connective tissue fiber in the tissue sections. The kit can be used on frozen sections, paraffin-embedded, or formalin-fixed.

If the stain comes out blue, it is an indicator of collagen. If it comes out red, then it represents muscle fibers. A black or blue outcome represents nuclei. (7)

What is a Pas-d stain and its purpose?

Pas-d stain or pas staining with diastase is primarily used to differentiate glycogen from other pas positive elements like mucin, which can be found on the tissue sample. A mucin can only be detected if the glycogen is digested with diastase and rinse out.

Pas-d stain can also be used to differentiate glycogen granules from other granules in some types of tumor. Analysing the glycogen deposits in the liver will help in diagnosing several enzyme deficiencies. (9, 10)

References:
  1. https://en.wikipedia.org
  2. aboratoryinfo.com
  3. http://bitesizebio.com
  4. www.ihcworld.com
  5. www.pathologyoutlines.com
  6. https://skinpathonline.wordpress.com
  7. www.ventana.com
  8. www.ncbi.nlm.nih.gov
  9. www.leicabiosystems.com
  10. www.ncbi.nlm.nih.gov

Saturday, May 14, 2016

Spider Angioma - Causes, Pictures and Treatment (Removal)

What is Spider Angioma?

A spider angioma is a small capillary that is dilated. When a small group of these capillaries are near the surface of the skin they can look like a spider web.[1] They are common and yet they are an abnormal group of capillaries near the skin's surface. [3] It is also called Nevus araneus, spider veins, vascular spider or spider telangiectasia.[4]
 

Symptoms of Spider Angioma

Spider angioma (Nevus araneus) has no symptoms besides its own appearance.[2] The most common place to find spider angiomas is on your face or torso. They can also be seen on ears, hands or forearms. Sometimes they appear as one and other times there are several.

The small red dot in the center and small lines of red which radiate from the center are telltale signs of spider angioma. It may only be about 1-10 mm in size. [1]

Spider angiomas occur in about 10-15% of the adult population.When they occur in children it is usually on the fingers or hands. [2] The presence of multiple spider angiomas, more than 5, can be a symptom of liver disease. [4]

A similar condition is cherry angioma which is usually dilated capillaries in a clump, that does not radiate out.
 

Spider Angioma Causes

Spider angiomas are generally benign resulting from dilated capillaries. There are six medical conditions which include spider angiomas as symptoms.
  1. Pregnancy
  2. Cirrhosis of the liver
  3. Primary biliary cirrhosis
  4. Hepatic diseases
  5. Hormonal contraception
  6. Wilson's Disease
Wilson's disease is a rare genetic disorder which can be fatal if it is not diagnosed. It is due to a high level of copper in the liver. [6] Spider angiomas which occur during pregnancy or with high estrogen content in your system will usually resolve themselves and disappear over time.

The dilated capillaries are a consequence of elevated estrogen levels in the blood. Because the liver is responsible for metabolizing estrogen, the presence of spider angiomas can be evidence of liver diseases. [4]
 

Spider Angioma Lesion Pictures

  
 Picture 1 : Spider Angioma on face 

  Picture 2 : Spider Angioma on nose


  Picture 3 : Spider Angioma (spider naevus) on face

Spider Angioma Diagnosis

Spider angioma (nevus araneus) has no other external symptoms besides its appearance. If you press on the center it disappears, but it returns when the pressure is removed.[3]
  • Taking the patient's medical history is also important and helpful.
  • Ask about a history of alcohol abuse.
  • Is the patient taking medication that can cause liver damage?
  • Is the female patient taking oral contraceptives or hormonal supplements?
  • Is she pregnant?
Generally, tests are not necessary to diagnose spider angioma. In some cases, it may be necessary to take a skin biopsy to eliminate basal cell carcinoma, particularly if the lesion is increasing in size. Sometimes blood tests are needed if the physician suspects a liver condition. [3] The spider angioma is not a vascular proliferation. It is the result of existing blood vessels which dilate. [2]
 

Spider Angioma Treatment (Removal)

Generally, no treatment is need for spider angiomas. Sometimes it is a cosmetic concern and the patient will request to have it removed. In these cases, laser treatment or electrocauterization therapy is the preferred treatment.[2] Do not try to scrape it off on your own with a razor. That can result in significant bleeding and infection. They will usually disappear in children, but often remain on adults. [6]
 

Natural Alternative Treatments

The focus for natural remedies is to improve your diet and drink more water. This will help to strengthen weak blood vessels by eating high fiber foods and others containing bioflavonoids. Examples are: blueberries, citrus fruit, cherries and adding vitamin C as a supplement. Also the bilberry (Vaccinium myrtillus) and ginkgo (Ginkgo bilboa) herbs are known to be helpful. [5]
 

When to Seek a Doctor's Help

If the spider angioma is growing or bleeding, you should consult your physician. If the lesion changes color or you begin suddenly to have multiple angiomas, that is time to seek medical attention. If you have a history of alcohol abuse, tell your doctor. Also if you begin to have yellowish skin or a swollen belly, contact your doctor right away. [1]  

References
  1. http://www.skinsight.com/adult/spiderAngioma.htm
  2. http://emedicine.medscape.com/article/1084388-followup
  3. http://www.nlm.nih.gov/medlineplus/ency/article/001095.htm
  4. http://en.wikipedia.org/wiki/Spider_angioma
  5. http://www.vashonorganics.com/WSWrapper.jsp?mypage=treatment_symptoms_spider%20angiomas.htm
  6. http://www.rightdiagnosis.com/symptoms/spider_angiomas/causes.htm

Saturday, May 23, 2015

Subclavian Steal Syndrome - Symptoms, Diagnosis and Treatment

Subclavian steal syndrome Definition

Subclavian steal syndrome is a rare but well known condition comprising of a group of neurological symptoms caused by the reversal of blood flow in the vertebral artery or internal thoracic artery caused due to blockage or narrowing of the Subclavian artery proximal to the origin of vertebral artery. [1, 2, 3]


Subclavian artery Normal anatomy

In a normal person, Aorta is the major vessel conducting blood from heart to other parts of the body through its branches. Subclavian artery is one of the major branches of Aorta. The left Subclavian artery arises directly from the Arch of Aorta, next to the origin of common carotid artery while the Right Subclavian artery arises along with the Right common carotid artery from a common branch of aorta, the brachiochephalic artery.

Vertebral artery is the first branch of Subclavian artery on either side and they supply the brain by taking part in the circle of Willis. Other branches of Subclavian artery supply blood to the arms and the upper part of trunk. Under normal condition, blood from aorta, flows through the Subclavian artery, in which a part of blood enter the vertebral artery to supply the brain and rest of it flows to other parts of upper body through its other branches. [1, 9]


Picture 1: Anatomy of Subclavian artery
Image Source: media-cache-ak0.pinimg.com

Picture 2: Anatomy of Circle of Willis showing both vertebral arteries joining to form basilar artery
Image Source: upright-health.com

Subclavian artery in Subclavian steal syndrome

The initiator of Subclavian steal syndrome is narrowing or blockage of Subclavian artery before the point of origin of the vertebral artery due to some reason. This results in increased resistance to the blood flow through the Subclavian artery in the side of blockage. Naturally, the blood flowing through the blood vessels of the opposite side increases taking the easier path and the blood flow decreased on the side of occlusion.

There is no problem until the blood flow through the affected side meets the demand of that part of the body. When there is an increase in demand as in the case of exercising the arm, there is dilatation of the blood vessels on the affected side. So, part of the blood reaching the circle of Willis from the vertebral artery of the unaffected side gets diverted to the arm, through the vertebral artery on the affected side, thus reversing its flow and stealing a part of brain’s blood supply. This is called the Subclavian steal phenomenon.[3]

When the diversion of blood is more and causes low blood supply to the brain resulting in various neurological symptoms, it is called Subclavian steal syndrome.[1,2,3]


Animation 1 – what happens in Subclavian steal syndrome? 


Subclavian steal syndrome Causes

Any disease condition that can result in the narrowing or blockage of the Subclavian artery to an extent leading to the reversal of blood flow through vertebral artery  and the neurological symptoms can cause Subclavian steal syndrome and there are only a few conditions causing it.

The common causes are

Atherosclerosis 
The formation of plaque in blood vessels due to excessive lipids in the blood, resulting in narrowing and reduced blood flow through the damaged vessel is called atherosclerosis and Left Subclavian artery is the most commonly affected branch of aorta [2]. It is the most common cause of Subclavian steal syndrome and the reason for the involvement of left Subclavian artery three times more than right Subclavian artery. The risk factors of atherosclerosis like smoking, increased blood pressure, diabetes etc, and act as indirect causes of Subclavian steal syndrome.


Picture 4:  Atherosclerotic plaque occluding a blood vessel
Image Source: dicardiology.com
Other uncommon causes are
  • Diseases causing narrowing of the vessels like Takayasu arteritis
  • Cervical Rib – extra rib causing occlusion by compressing the Subclavian artery
  • Abnormal development of the artery by birth as in Interrupted Aortic arch, thoracic aortic dissection etc.
  • Surgeries like Blalock Taussig shunt as treatment of tetrology of fallot and radiation. [1, 2]

Subclavian steal syndrome Symptoms

Most of the people with a blockage of Subclavian artery lead their life without any symptoms and thus without knowing about the presence of a problem. But Subclavian steal phenomenon can be called as Subclavian steal syndrome only if the following symptoms are present.

The neurological problems are caused due to reduced blood supply to brain caused by excessive stealing of blood from the cerebral circulation and the symptoms in the arm are related to the reduced blood supply due to the block in Subclavian artery. They are
  • A feeling of earth around them revolving [vertigo]
  • A feeling of faintness
  • Fainting spells
  • Ringing sound in the ear
  • Difficulty in speaking
  • Double vision
  • Memory problems
  • Arterial pulse on the affected side may be faintly felt or absent
  • Blood Pressure :- In a normal person, the blood pressure recorded on both arms are equal. In Subclavian steal syndrome, the blood pressure recorded in the affected arm is lower than the unaffected side and the difference is greater than 25 mm Hg. It is highly uncommon for Subclavian steal syndrome to present without any effect in the blood pressure. If there are neurological symptoms similar to Subclavian steal syndrome with equal blood pressure on both arms, one must think about proximal vertebral artery obstruction.
  • Increase in severity of the symptoms during physical exercised involving the affected arm.[1,2, 4]
  • When the left vertebral artery arise directly from aorta, as in 2% of the population,  these symptoms are absent[5]

Subclavian steal syndrome Diagnosis and Radiology

While the asymptomatic and people with mild symptoms remain undiagnosed of the blockage in their vessel, a clinician can confirm the diagnosis based on the combination of
  • complete history taking
  • physical examination
  • eliciting the symptoms by exercising the arm or using a BP cuff
  • Imaging studies to visualize the narrowing or occlusion of the Subclavian artery
  • Laboratory investigations to find the cause[6,7]

Doppler ultrasound

  • Doppler ultrasound shows the reversed flow of blood in the vertebral artery.
  • It detects the velocity of the blood flow showing the increase in velocity in the affected arm after exercising the arm
  • Though the obstruction in the proximal segment of Subclavian artery is not clearly visualized the probe, the blood flow in the distal segment shows a characteristic pattern called parvus tardus waveform.

CT Angiography

CT angiography is an excellent modality to visualize the obstruction and other lesion in the Subclavian artery. In this process, a contrast agent containing iodine is injected which trace the path of blood flow. The enhancement of the vertebral artery on the affected side is delayed. When there is a plan to treat the condition simultaneously by one of the catheter based techniques, a 4 vessel arteriography is the choice of imaging.


Picture 5 : CT angiogram showing occlusion of proximal left Subclavian artery http://emedicine.medscape.com/article/418203-overview#a20

MRI angiography

This is the choice of visualizing the lesion in people who cannot tolerate the contrast agents due to kidney diseases. But MRI overweighs the occlusion, resulting in more false positive results.


Picture 6: MRI angiogram showing block in proximal Subclavian artery
Image Source: radiologypics.files.wordpress.com

Plain chest radiograph : to diagnose cervical rib



Picture 7:  radiograph showing cervical rib
image source : klinikaikozpont.u-szeged.hu

Electrocardiogram : to diagnose co existing heart disease caused by atherosclerosis.

Blood investigations  : like fasting lipid profile and blood sugar levels

Subclavian steal syndrome Treatment

The treatment modality of Subclavian steal syndrome is mainly surgical and is reserved for people with severe symptoms and chronic obstruction of the Subclavian artery. Surgery is done to relieve the obstruction of the Subclavian artery and restore the blood flow of vertebral artery towards the brain.

The surgical modality gaining popularity is Endovascular surgeries which avoid all the cutting open and involves clearing up of the obstruction from inside the blood vessel using a catheter. It can be done as an outpatient procedure and the recovery period is reasonably short with fewer complications during and after the surgical procedure. The recurrence rate is very low. These are the common way of treating a proximal Subclavian artery block.

Stent or balloon angioplasty

Stenting is a process in which a prosthetic material is used to widen the occlusion and is retained in the spot to maintain the blood flow. In balloon angioplasty, an inflatable balloon is introduced through the catheter and the balloon is inflated at the narrowed part which widens it. The efficacy of both the procedures is fairly similar. Primary Stenting of Subclavian artery is the treatment of choice.

Subclavian bypass graft

In this procedure, the blood flow is rerouted to the arms by bypassing the obstruction. This can be done by using a prosthetic bypass or using the saphenous vein from the same patient. Once the normal blood flow is restored in the vertebral artery, the prognosis is excellent.

Transposition

It is another surgical method in which the Subclavian artery is transposed to a new spot on the side of common carotid artery. No prosthetic material is needed for this procedure. But this procedure involves operating in a field with many other important structures and meticulous care should be taken not to injure them.

Endarterectomy

Endarterectomy is a procedure which involves opening of the chest, accessing the obstructed part of the artery, opening it and removing the plaque. This results in widening the obstructed segment and restoring the blood flow. This method is no longer followed because of the failure rates and the post op complications and the mortality rate and the recurrence of the obstruction.

Adjunct medications

In patients with atherosclerosis, oral antiplatelet medications are prescribed for life long to prevent the recurrence of atherosclerotic plaque and to prevent other diseases like heart attack and stroke which are also fairly common with atherosclerosis.

Last but not the least, lifestyle modifications which can reduce atherosclerosis like quitting cigarettes, taking a diet with less fat content and maintain physical fitness can prevent the progression of a Subclavian artery narrowing from causing Subclavian steal phenomenon. [7]

References:
  1. http://en.wikipedia.org/wiki/Subclavian_steal_syndrome
  2. http://emedicine.medscape.com/article/462036-overview
  3. http://radiopaedia.org/articles/subclavian-steal-syndrome
  4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2640015/
  5. http://www.patient.co.uk/doctor/Subclavian-Steal-Phenomenon.htm
  6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614262/
  7. http://www.medscape.com/viewarticle/410768_1
  8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2827228/
  9. http://en.wikipedia.org/wiki/Subclavian_artery

Friday, May 8, 2015

How to get rid of Fordyce Spots on Lips

What is Fordyce spot?


Fordyce spot is a harmless medical condition caused by the presence of prominent sebaceous gland in an abnormal site in the body. It is also known as FORDYCE GRANULE or FOX FORDYCE DISEASE [1, 2]

Where does Fordyce spots appear?


Fordyce spot mostly occur in LIPS along the border where the smooth pink surface of the lip meets the oral skin. It may also present in the INNER ASPECT OF CHEEK and anywhere in the oral cavity. Other less common places are scrotum, shaft of penis, foreskin of penis in men where they are called as TYSON’S GLANDS and labia in women. [1, 2, 3]

Picture 1 – Fordyce spot on lip 

What causes Fordyce spots on lips?


Sebaceous glands are parts of the skin similar to the sweat gland. A sebaceous gland is situated in the deeper layer of skin called DERMIS and they produce a chalky white oily paste like substance called SEBUM.  Normally, a sebaceous gland opens into a hair follicle and releases the sebum into it. When the sebaceous gland lies in abnormal sites like the lip where there are no hair follicles it does not have an outlet to release the sebum. This causes building up of sebum inside the gland, making it to appear prominent. Hence they are called as SEBACEOUS PROMINENCE and this causes the Fordyce spot on lip.


Image 2 : – Normal sebaceous gland 

How does Fordyce spot appear? [3]

  •     Fordyce spot on the lip appear as a small elevation of size 1 – 3 mm.
  •     It is pale, white or red and looks like a miniature peanut.
  •     It is always painless
  •     It is not itchy
  •     It is not associated with any other systemic illness or symptoms like fever

Does Fordyce spot go away?


YES. In most cases, Fordyce spot in lip resolve spontaneously within couple of weeks. As it is a natural condition without any underlying disease, the chances are more for it to disappear automatically if it is left untouched without pinching or squeezing its content out.
Is Fordyce spot contagious?

NO. Fordyce spot is not contagious. It is not a disease or an infection that spreads from one person to another. So don’t get scared that you can catch Fordyce spot in lips by kissing someone. Also, Fordyce spot cannot get infected, as there is no inlet for the germs, same as there is no outlet for the sebum. It can get only infected if it’s broken up by biting into it accidentally or squeezing its contents out.[3,6]

Who gets Fordyce spots?


Fordyce spot can be present in anyone from a newborn to adult. But the chance of getting a Fordyce spot increases around the PUBERTAL AGE when there is increased activity of the sebaceous gland under the influence of the raging hormones. About 85 -90% people have Fordyce spot either in lip or in genitals and men are found to have Fordyce spot more than women. The cause for this male predilection is not known.[6,8]

Fordyce spot treatment and cure


        As said above, Fordyce spot is nothing to be worried about. Skin specialists advice against treatment to Fordyce spot because it does not cause any discomfort while some of the treatment options have undesirable side effects and some may form permanent scars. But most people approach a dermatologist for Fordyce spot only for cosmetic reasons.

So, how to get rid of Fordyce spot?


         Wait and watch: A Fordyce spot disappear or shrink in a small span of time. So wait and watch for couple of weeks.

        Vitamins: vitamins like B complex regulate the sebum secretion and reduce the prominence of the gland.

        Adding garlic to the diet can resolve the spots. The reason behind this is not known, probably because of the minerals like selenium in it and chemicals like allicin.

        Carbon dioxide laser: A laser is a cutting method that uses laser beam to vaporize the unwanted tissues. This laser is directed to the prominent gland which then destroys the tissue without bleeding. It causes complete cure to Fordyce spot and it doesn’t reappear. Sometimes it may cause minimal scarring. The epithelialisation of the spot occurs within 2 weeks time. The success of co2 laser technique has higher success rate when it is combined with topical application of tricloracetic acid.
 
        Pulse dye laser: In this technique the laser beam is directed as short repeated pulses. This is more expensive but causes lesser scarring. It is also a permanent cure for Fordyce spot.

        Cryosurgery:   This technique is similar to laser and the only difference is that, excessive cold is used to destroy the tissue by freezing it. This is done by using liquid nitrogen or carbon dioxide. This may cause some damage to some of the surrounding tissue. [9]

        Other techniques to remove Fordyce spot are Micro puncture, Electro desiccation, Photodynamic therapy and chemical cauterization.

       Topical isoteretinoin gel combined with alpha hydroxyacid agent gives relief in couple of weeks. But when used for a long period it cause unwanted side effects like dry skin, burning, itching, thinning of hair etc. [2, 3, 6, 7, 8]

So, if you are doubtful of having Fordyce spot and want to get it treated, check with your dermatologist and weigh your treatment options as some techniques work better than others due to individual variability.
   
   
References:   
  • http://en.wikipedia.org/wiki/Fordyce_spots
  • http://www.dermnetnz.org/acne/fordyce.html
  • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283840/
  • http://www.aocd.org/?page=FordyceSpots
  • http://www.ncbi.nlm.nih.gov/pubmed/12859392
  • http://www.ncbi.nlm.nih.gov/pubmed/7662086
  • Article on Treatment of Fordyce granules with a CO2 laser: report of two cases Tratamento dos gr├ónulos de Fordyce com laser de CO2 – Relato de dois casos
  • http://www.nhs.uk/medicine-guides/pages/MedicineSideEffects.aspx?condition=Acne&medicine=isotretinoin&preparation
  • http://en.wikipedia.org/wiki/Cryosurgery