Pathogenesis

Pulmonary fibrosis involves gradual replacement of normal lung parenchyma with fibrotic tissue. Thickening of scar tissue causes irreversible decrease in oxygen diffusion capacity. In addition, decreased compliance makes pulmonary fibrosis a restrictive lung disease. It is the main cause of restrictive lung disease that is intrinsic to the lung parenchyma. In contrast, quadriplegia and kyphosis are examples of causes of restrictive lung disease that do not necessarily involve pulmonary fibrosis.

Etiology

Pulmonary fibrosis may be a secondary effect of other diseases, most of them being classified as interstitial lung diseases, e.g. autoimmune disorders, viral infections or other microscopic injuries to the lung. However, it may also appear without any known cause, then termed "idiopathic". Most of the idiopathic cases can be diagnosed as idiopathic pulmonary fibrosis, a diagnosis of exclusion, yet having a characteristic set of histologic/pathologic features known as usual interstitial pneumonia (UIP). In either case, there is a growing body of evidence which points to a genetic predisposition. For example, a mutation in Surfactant protein C (SP-C) has been found to exist in families with a history of pulmonary fibrosis.

Diseases and conditions that may cause pulmonary fibrosis as a secondary effect include:

• Inhalation of environmental and occupational pollutants, such as in asbestosis, silicosis and exposure to certain gases. Coal miners, ship workers and sand blasters among others are at higher risk.
• Hypersensitivity pneumonitis, most often resulting from inhaling dust contaminated with bacterial, fungal, or animal products.
• Cigarette smoking can increase the risk or make the illness worse.
• Some typical connective tissue diseases such as rheumatoid arthritis, SLE and scleroderma
• Other diseases that involve connective tissue, such as sarcoidosis and Wegener's granulomatosis.
• Infections
• Certain medications, e.g. nitrofurantoin
• Radiation therapy to the chest

Symptoms and diagnosis

Symptoms of pulmonary fibrosis are mainly:

• Shortness of breath, particularly with exertion
• Chronic dry, hacking coughing
• Fatigue and weakness
• Chest discomfort
• Loss of appetite and rapid weight loss

Pulmonary fibrosis is suggested by a history of progressive shortness of breath (dyspnea) with exertion. Sometimes crackles can be heard in the chest with stetoscope. A chest x-ray may or may not be abnormal, but high Resolution CT will frequently demonstrate abnormalities.

The diagnosis can be confirmed by lung biopsy. An open surgical biopsy, meaning that the chest wall is surgically opened under general anesthesia to remove a portion of lung tissue, may be necessary to obtain enough tissue to make an accurate diagnosis. The removed tissue is examined histopathologically by microscopy to confirm the presence of fibrosis.

Misdiagnosis is common because the origin and development of the disease is not completely understood. There is varying terminology and lack of standard diagnostic criteria and this complicates the gathering of accurate information about pulmonary fibrosis.

On spirometry, as a restrictive lung disease, both the FEV1 (Forced Expiratory Volume in 1 Second) and FVC (Forced Vital Capacity) are reduced so the FEV1/FVC ratio is normal or even increased in contrast to obstructive lung disease where this ratio is reduced. The values for residual volume and total lung capacity are generally decreased in restrictive lung disease[7].

Prevalence

Five million people worldwide are affected by pulmonary fibrosis. In the United States there are over 500,000 patients with pulmonary fibrosis. The actual numbers may be significantly higher due to misdiagnosis. Typically, patients are in their forties and fifties when diagnosed.

Treatment and prevention

Scarring is permanent once it has developed. Slowing in the progression and prevention depends on the underlying cause:

• For idiopathic pulmonary fibrosis (IPF) there is currently no effective treatment or cure. There are pharmacological agents in the experimental phase intended to prevent scarring. Anti-inflammatory agents have only limited success in reducing the fibrotic progress.
• Some of the other types of fibrosis, such as nonspecific interstitial pneumonitis (NSIP), may respond to immunosuppressive therapy such as such as corticosteroids. However, only a minority of patients respond to corticosteroids alone, so additional immunosuppressants, such as cyclophosphamide, azathioprine, methotrexate, penicillamine, and cyclosporine may be used. Colchicine has also been used with limited success. There are ongoing trials with newer drugs such as IFN-γ, mycophenolate mofetil, and pirfenidone.
• Hypersensitivity pneumonitis is prevented from becoming aggravated by avoiding contact with the causative material.
• Oxygen supplementation improves the quality of life and exercise capacity. Lung transplantation may be considered for some patients.

Complications

Hypoxia caused by pulmonary fibrosis can lead to pulmonary hypertension, which, in turn, can lead to heart failure of the right ventricle. This can be prevented with oxygen supplementation.

Pulmonary fibrosis may also cause increased risk for pulmonary emboli, which can be prevented by anticoagulants.
 

Hard Fibroma

The hard fibroma (fibroma durum) consists of many fibres and few cells, e.g. in skin it is called dermatofibroma (fibroma simplex or nodulus cutaneous). A special form is the keloid, which derives from hyperplastic growth of scars.

Soft Fibroma

The soft fibroma (fibroma molle) or fibroma with a shaft (acrochordon, skin tag, fibroma pendulans) consist of many loosely connected cells and less fibroid tissue. It mostly appears at the neck, armpits or groins. The photo shows a soft fibroma of the eyelid.

Other types of fibroma

• The fibroma cavernosum or angiofibroma, consists of many often dilated vessels, it is a vasoactive tumor occurring almost exclusively in adolescent males.
• The cystic fibroma (fibroma cysticum) has central softening or dilated lymphatic vessels.
• The myxofibroma (fibroma myxomatodes) is produced by liquefaction of the underlying soft tissue.
• The cemento-ossifying fibroma is hard and fibrous, most frequently seen in the jaw or mouth, sometimes in connection with a fracture or another type of injury.
• Other fibromas: chondromyxoid fibroma, desmoplasmic fibroma, nonossifying fibroma, ossifying fibroma, perifollicular fibroma, pleomorphic fibroma etc.
• Ovarian fibroma appears in the sex cord-stromal tumour group of ovarian neoplasms. Ovary fibromas are most frequent during middle age, and rare in children. Upon gross pathological inspection, ovary fibromas are firm and white or tan. Variants with edema are especially likely to be associated with Meig's syndrome. On microscopic examination, there are intersecting bundles of spindle cells producing collagen. There may be thecomatous areas (fibrothecoma). The presence of an ovarian fibroma can cause ovarian torsion in some cases.

Treatment

Benign fibromas can be removed or left alone. A physician should examine the fibroma and determine whether it may be malignant. If there is any question as to whether it may be cancer-related, it should be removed. This is usually a brief outpatient procedure.

• Fibroids is the common term for Uterine fibroids; leiomyoma originating in the uterus. It is a benign neoplasm composed of smooth muscle cells.
• A fibroid tumor is another name for a fibroma, a tumor of fibrous connective tissue

Uterine fibroids

A uterine fibroid (also uterine leiomyoma, myoma, fibromyoma, leiofibromyoma, fibroleiomyoma, and fibroma) (plural of … myoma is …myomas or …myomata) is a benign (non-cancerous) tumor that originates from the smooth muscle layer (myometrium) and the accompanying connective tissue of the uterus. Fibroids are the most common benign tumors in females and typically found during the middle and later reproductive years. While most fibroids are asymptomatic, they can grow and cause heavy and painful menstruation, painful sexual intercourse, and urinary frequency and urgency. Uterine fibroids is the major indication for hysterectomy in the US.  Fibroids are often multiple and if the uterus contains too many leiomyomatas to count, it is referred to as uterine leiomyomatosis. The malignant version of a fibroid is uncommon and termed a leiomyosarcoma.

Prevalence

A relatively large submucosal leiomyoma; it fills out the major part of the endometrial cavityAbout 20-40% of women will be diagnosed with leiomyoma.  The condition is about twice as common in black women as white women.  Estrogen receptors on fibroids cause them to respond to estrogen stimulation during the reproductive years. During hypoestrogenic states, such as after menopause, leiomyoma are expected to shrink. Leiomyoma are more common in overweight women (because of increased estrogen from adipose aromatase activity).

Symptoms

Generally, symptoms relate to the location of the lesion and its size (mass effect). Important symptoms include abnormal gynecologic hemorrhage, heavy or painful periods, abdominal discomfort or bloating, painful defecation, back ache, urinary frequency or retention, and in some cases, infertility.  There may also be pain during intercourse, depending on the location of the fibroid. During pregnancy they may be the cause of miscarriage, bleeding, premature labor, or interference with the position of the fetus.

Fibroids, particularly when small, may be entirely asymptomatic. The U.S. Department of Health & Human Services states that "Fibroids are almost always benign (not cancerous). Rarely (less than one in 1,000) a cancerous fibroid will occur. This is called leiomyosarcoma. Doctors think that these cancers do not arise from an already-existing fibroid. Having fibroids does not increase the risk of developing a cancerous fibroid. Having fibroids also does not increase a woman's chances of getting other forms of cancer in the uterus."

While fibroids are common, they are not a typical cause for infertility accounting for about 3% of reasons why a woman may not have a child.  Typically in such cases a fibroid is located in a submucosal position and it is thought that this location may interfere with the function of the lining and the ability of the embryo to implant.  Also larger fibroids may distort or block the fallopian tubes.

Diagnosis

While a bimanual examination typically can identify the presence of larger fibroids, gynecologic ultrasonography (ultrasound) has evolved as the standard tool to evaluate the uterus for fibroids. Sonography will depict the fibroids as focal masses with a heterogeneous texture, which usually cause shadowing of the ultrasound beam. The location can be determined and dimensions of the lesion measured. Also magnetic resonance imaging (MRI) can be used to define the depiction of the size and location of the fibroids within the uterus.

Imaging modalities cannot clearly distinguish between the benign uterine leiomyoma and the malignant uterine leiomyosarcoma, however, the latter is quite rare. However fast growth or unexpected growth such as enlargement of a lesion after the menopause raise the level of suspicion that the lesion might be a sarcoma. Also, with advanced malignant lesions there may be evidence of local invasion. A more recent study has suggested that diagnostic capabilities using MRI have improved the ability to detect sarcomatous lesions.  Biopsy is rarely performed and if performed, is rarely diagnostic. Should there be an uncertain diagnosis after ultrasounds and MRI imaging, surgery is generally indicated.

Other imaging techniques that may be helpful specifically in the evaluation of lesions that affect the uterine cavity are hysterosalpingography or sonohysterography.

Coexisting disorders

Fibroids that lead to heavy vaginal bleeding lead to anemia and iron deficiency. Due to pressure effects gastrointestinal problems are possible such as constipation and bloatedness. Compression of the ureter may lead to hydronephrosis. Fibroids may also present alongside endometriosis, which itself may cause infertility.Adenomyosis may be mistaken for or coexist with fibroids.

Treatment

Expectant management

The presence of fibroids does not mean that they need to be treated; lesions can be managed expectantly depending on the symptomatology and presence of related conditions. Thus most cases of fibroids are managed by "watchful waiting" which includes periodic sonographic assessment. After menopause fibroids shrink and it is unusual for fibroids to cause problems.

The presence of symptomatic uterine fibroids can be solved by:

Surgery

Surgery: Surgical removal of a uterine fibroid usually takes place via hysterectomy, in which the entire uterus is removed, or myomectomy, in which only the fibroid is removed. It is possible to remove multiple fibroids during a myomectomy. Although a myomectomy cannot prevent the recurrence of fibroids at a later date, such surgery is increasingly recommended, especially in the case of women who have not completed bearing children or who express an explicit desire to retain the uterus. There are three different types of myomectomy:

• In a hysteroscopic myomectomy, the fibroid is removed by the use of a resectoscope, an endoscopic instrument that can use high-frequency electrical energy to cut tissue. Hysteroscopic myomectomies can be done as an outpatient procedure, with either local or general anesthesia used. Hysteroscopic myomectomy is most often recommended for submucosal fibroids. A French study collected results from 235 patients suffering from submucous myomas who were treated with hysteroscopic myomectomies; in none of these cases was the fibroid greater than 5 cm.
• A laparoscopic myomectomy requires a small incision near the navel. The physician then inserts a laparoscope into the uterus and uses surgical instruments to remove the fibroids. Studies have suggested that laparoscopic myomectomy leads to lower morbidity rates and faster recovery than does laparotomic myomectomy.  As with hysteroscopic myomectomy, laparoscopic myomectomy is not generally used on very large fibroids. A study of laparoscopic myomectomies conducted between January 1990 and October 1998 examined 106 cases of laparoscopic myomectomy, in which the fibroids were intramural or subserous and ranged in size from 3 to 10 cm.
• A laparotomic myomectomy (also known as an open or abdominal myomectomy) is the most invasive surgical procedure to remove fibroids. The physician makes an incision in the abdominal wall and removes the fibroid from the uterus. A particularly extensive laparotomic procedure may necessitate that any future births be conducted by Caesarean section. Recovery time from a laparatomic procedure is generally expected to be four to six weeks.

Uterine artery embolization

Uterine artery embolization (UAE): Using interventional radiology techniques, the interventional radiologist occludes both uterine arteries, thus reducing blood supply to the fibroid  . A small catheter (1 mm in diameter) is inserted into the femoral artery at the level of the groin under local anesthesia. Under imaging guidance, the interventional radiologist will enter selectively into both uterine arteries and inject small (500 µm) particles that will block the blood supply to the fibroids. A patient will usually recover from the procedure within a few days. The UAE results in the supposed shrinking of the fibroids and of the uterus, thus alleviating the symptoms. However, it is important to note that significant adverse effects resulting from uterine artery embolization have been reported and documented in the medical literature including death, infection, misembolization, loss of ovarian function, unsuccessful fibroid expulsion, pain, foul vaginal odor, hysterectomy, and failure of embolization surgery.

Radiofrequency Ablation

Radiofrequency Ablation: One of the newest minimally invasive treatments for fibroids is radiofrequency ablation  . In this technique the fibroid is shrunk by inserting a needle-like device into the fibroid through the abdomen and heating it with low frequency electrical currents. This new treatment is still under investigation in a Phase 3 clinical trial across 6 sites in the US. The treatment is a potential option for women who have fibroids, have completed child-bearing and want to avoid a hysterectomy.

Medication

Primary

Medical therapy: Currently, the only medication approved to reduce fibroids are the Gonadotropin-releasing hormone analogs. GNRH analogs, however, are short term treatments only because they lead to estrogen-deficiency and may cause osteoporosis. Aromatase inhibitors have been used experimentally to reduce fibroids. Progesterone antagonists have been shown in small studies to decrease the size of uterine fibroids. Thus mifepristone was effective in a placebo-controlled pilot study. Selective progesterone receptor modulators, such as Progenta, have been under investigation.

Secondary

A number of secondary medications are in use to alleviate symptoms caused by fibroids. This allows an otherwise expectant approach to bring the patient hopefully to menopause when symptoms naturally regress. Thus oral contraceptive pills, either combination pills with low-dose estrogens or progestin-only, are prescribed in an effort to reduce uterine bleeding and cramps. Such medications seem to have little or no effect on the size of the lesions.  Anemia may have to be treated with iron supplementation. NSAIDs can be used to reduce painful menses.

Other

HIFU (High intensity focused ultrasound), also called Magnetic Resonance guided Focused Ultrasound, is a non-invasive intervention (requiring no incision) that uses high intensity focused ultrasound waves to ablate (destroy) tissue in combination with Magnetic Resonance Imaging (MRI), which guides and monitors the treatment. This technique is relatively new; it was approved by the FDA in 2004.

The use of vitex herbal medicine lacks supporting evidence.