Edit concept Question Editor Create issue ticket

Pulmonary Sarcoidosis

Pulmonary sarcoidosis is characterized by the presence of noncaseating granulomas, which are abnormal collections of cells in the lungs. While this disease may be benign and self-limiting, it can result in severe sequelae. 


Presentation

Numerous factors contribute to the clinical picture including ethnicity, the length of illness, other organ involvement and granulomatous activity. Patients may present with nonspecific symptoms. Some will exhibit features related to specific sarcoid organ involvement [9]. A third of patients, especially black people and Asian Indians, present with weight loss, malaise and fever [3]. 30% to 50% of individuals are diagnosed incidentally on routine chest X-ray.

More than 90% of patients with sarcoidosis exhibit pulmonary involvement. Initially the disease process is interstitial. Symptomatic patients report a nonproductive cough, respiratory difficulty, dyspnea, and swollen lymph nodes. This disease will either resolve spontaneously or result in progressive respiratory failure. The latter manifestation is correlated to fibrotic lungs.

Pulmonary sarcoidosis is classified into four stages. The first stage is largely asymptomatic (95% of patients) with a spontaneous remission rate of 55% to 90% [3] [9]. The second stage is symptomatic in over half of patients (58%) and remission occurs in 40% to 70% of patients [3] [9]. The advanced stages are usually symptomatic, progressive, and characterized by significant lung dysfunction, fibrosis and airway limitation. Dyspnea and persistent cough are often observed. Furthermore, remission rates in the later stages are below 20% (with stage four demonstrating very low rates) [3] [9].

Serious sequelae include bronchiectasis, pulmonary hypertension, respiratory failure, and cardiac sarcoidosis. Note that extrapulmonary involvement can be observed as well. Sarcoidosis can manifest in the eyes (chronic uveitis), blood vessels (vasculitis), skin (erythema nodosum), heart, bone marrow, kidneys, liver, etc. It can also present with neurological symptoms. 

Fever
  • Fever and uveitis no longer recurred after 6 months of medication.[ncbi.nlm.nih.gov]
  • We report an 11 yr old girl who presented with chronic cough, low grade fever, recent exposure to tuberculosis and hilar lymphadenopathy. She was provisionally diagnosed as pulmonary tuberculosis and treated accordingly.[ncbi.nlm.nih.gov]
  • A 33-year-old black man presented with 4 days of headache and fever. He had subsequent development of respiratory failure on the seventh hospital day.[ncbi.nlm.nih.gov]
  • A 48-year-old man with dyspnea, cough, and fever was found to have a diffuse ground-glass pulmonary lesion without lymphadenopathy on chest X-ray.[ncbi.nlm.nih.gov]
  • A 27-year-old man presented with nonproductive cough and high fever lasting for 3 weeks. A chest radiograph showed multiple areas of consolidation and cavitary shadows in the lungs.[ncbi.nlm.nih.gov]
Fatigue
  • Persistence of fatigue, or new onset fatigue, may be encountered during treatment, possibly as an adverse effect of corticosteroid therapy.[ncbi.nlm.nih.gov]
  • Patients with sarcoidosis with extrapulmonary involvement are more symptomatic (fatigue), have higher SACE levels and more deteriorating HRCT findings, to which clinicians should pay attention.[ncbi.nlm.nih.gov]
  • At week 24, there was a decrease in the dose of prednisone, and improvements in DLCO, King's Sarcoidosis Questionnaire health status and fatigue score. There was no significant change in FVC % predicted.[ncbi.nlm.nih.gov]
  • We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: May 13, 2019[patientslikeme.com]
  • As new and more potent antiinflammatory agents have been developed, it is clear that there are other factors that burden the patient with sarcoidosis, including fatigue and sarcoidosis-associated pulmonary hypertension.[atsjournals.org]
Weight Loss
  • After being treated for a presumed asthma exacerbation with prednisone, she experienced worsening dyspnea, night sweats, and unintentional weight loss. Further evaluation revealed a large left lower lobe mass and hilar lymphadenopathy.[ncbi.nlm.nih.gov]
  • A third of patients, especially black people and Asian Indians, present with weight loss, malaise and fever. 30% to 50% of individuals are diagnosed incidentally on routine chest X-ray.[symptoma.com]
  • However, some patients do exhibit symptoms such as: Shortness of breath (dyspnea) Wheezing and/or a chronic cough Fatigue Night sweats Weight loss Swollen lymph nodes Fever Pain in the chest, joints, and bones While the exact cause of pulmonary sarcoidosis[tgh.org]
  • Non-specific symptoms: Fever Weight loss Night sweats Fatigue Symptoms related to the lung: Shortness of breath Wheezing Chest pain Recurring chest colds Less exercise tolerance Symptoms related to lymph nodes: Enlarged lymph nodes in the neck, under[health.ucsd.edu]
Constitutional Symptom
  • A solitary lung mass is a rare finding for pulmonary sarcoidosis, and with its associated constitutional symptoms, it strongly mimics a malignancy.[ncbi.nlm.nih.gov]
Cough
  • Cough reflex sensitivity to capsaicin, objective 24-h cough counts, cough-specific health status, cough severity and cough triggers were measured.[ncbi.nlm.nih.gov]
  • But her cough and the nodular shadows were persisted, therefore the treatment was replaced with budesonide at 800 microg/day. Two months later, her dry cough subsided and pulmonary shadows improved.[ncbi.nlm.nih.gov]
  • We report an 11 yr old girl who presented with chronic cough, low grade fever, recent exposure to tuberculosis and hilar lymphadenopathy. She was provisionally diagnosed as pulmonary tuberculosis and treated accordingly.[ncbi.nlm.nih.gov]
  • A 48-year-old man with dyspnea, cough, and fever was found to have a diffuse ground-glass pulmonary lesion without lymphadenopathy on chest X-ray.[ncbi.nlm.nih.gov]
  • A 27-year-old man presented with nonproductive cough and high fever lasting for 3 weeks. A chest radiograph showed multiple areas of consolidation and cavitary shadows in the lungs.[ncbi.nlm.nih.gov]
Dyspnea
  • After being treated for a presumed asthma exacerbation with prednisone, she experienced worsening dyspnea, night sweats, and unintentional weight loss. Further evaluation revealed a large left lower lobe mass and hilar lymphadenopathy.[ncbi.nlm.nih.gov]
  • We herein report the case of a 40-year-old woman with pulmonary sarcoidosis who presented with dyspnea on exertion.[ncbi.nlm.nih.gov]
  • A 48-year-old man with dyspnea, cough, and fever was found to have a diffuse ground-glass pulmonary lesion without lymphadenopathy on chest X-ray.[ncbi.nlm.nih.gov]
  • The patient was a 55-year-old man whose dyspnea had been misdiagnosed and who had been treated for chronic obstructive pulmonary disease.[ncbi.nlm.nih.gov]
  • Common presenting symptoms include cough, dyspnea and chest pain. Massive hemoptysis is a rare presentation in sarcoidosis. There are a few reports on massive hemoptysis in sarcoidosis.[ncbi.nlm.nih.gov]
Dry Cough
  • In the first case, fluticasone at 400 microg/day was initiated, because dry cough and small nodular shadows on chest X-ray persisted for six months.[ncbi.nlm.nih.gov]
  • In the lungs, it can cause a dry cough, mild chest pain, or shortness of breath. How Serious is Sarcoidosis? Nobody can predict how sarcoidosis will affect one person verses another. It is not serious in over half the cases.[athenspulmonary.com]
  • The most common symptoms of pulmonary sarcoidosis are shortness of breath, which often gets worse with activity; dry cough that will not go away; chest pain; and wheezing.[hopkinsmedicine.org]
  • If symptoms do occur, they can include dry cough, tightness in the chest, and tiredness. Wheezing, shortness of breath, skin rashes, joint pain, kidney stones, vision problems, and loss of appetite can also occur.[fairview.org]
Pharyngitis
  • Esophagram revealed a large amount of contrast pooling in pharyngeal recesses with intermittent laryngeal aspiration.[ncbi.nlm.nih.gov]
Upper Abdominal Pain
  • We report a case of LCA in a 43-year old male patient who presented with a loss of appetite and intermittent upper abdominal pain. Computed tomography showed multiple hypoattenuating splenic lesions which were hyperechogenic on abdominal ultrasound.[ncbi.nlm.nih.gov]
Chest Pain
  • Common presenting symptoms include cough, dyspnea and chest pain. Massive hemoptysis is a rare presentation in sarcoidosis. There are a few reports on massive hemoptysis in sarcoidosis.[ncbi.nlm.nih.gov]
  • This case study describes a 38-year-old male, who presented with chest pain, high-grade fever, arthralgias and a skin rash accompanied by bilateral hilar lymphadenopathy on his chest radiograph.[ncbi.nlm.nih.gov]
  • In the lungs, it can cause a dry cough, mild chest pain, or shortness of breath. How Serious is Sarcoidosis? Nobody can predict how sarcoidosis will affect one person verses another. It is not serious in over half the cases.[athenspulmonary.com]
  • The most common symptoms of pulmonary sarcoidosis are shortness of breath, which often gets worse with activity; dry cough that will not go away; chest pain; and wheezing.[hopkinsmedicine.org]
Night Sweats
  • After being treated for a presumed asthma exacerbation with prednisone, she experienced worsening dyspnea, night sweats, and unintentional weight loss. Further evaluation revealed a large left lower lobe mass and hilar lymphadenopathy.[ncbi.nlm.nih.gov]
  • However, some patients do exhibit symptoms such as: Shortness of breath (dyspnea) Wheezing and/or a chronic cough Fatigue Night sweats Weight loss Swollen lymph nodes Fever Pain in the chest, joints, and bones While the exact cause of pulmonary sarcoidosis[tgh.org]
  • Non-specific symptoms: Fever Weight loss Night sweats Fatigue Symptoms related to the lung: Shortness of breath Wheezing Chest pain Recurring chest colds Less exercise tolerance Symptoms related to lymph nodes: Enlarged lymph nodes in the neck, under[health.ucsd.edu]
  • sweats Pain in the joints and bones Skin rashes, lumps, and color changes on face, arms, or shins Swollen lymph nodes Weight loss The symptoms of pulmonary sarcoidosis may look like other conditions or medical problems.[hopkinsmedicine.org]

Workup

Obtain a thorough history (including that of the family) and a detailed physical exam.  Diagnosis is established through radiologic and histologic identification of noncaseating granulomas in the lungs. Additionally, other etiologies should be excluded as there are many granulomatous diseases such as tuberculosis, Crohn disease, hypersensitivity pneumonitis, fungal disease, and so forth. The goal of undertaking diagnostic procedures is to demonstrate the stage, extrapulmonary organ involvement and its degree of severity, the stability of the disease, and to guide therapeutic decision-making [3].

A significant component of the workup is a biopsy of lymph node or pulmonary tissue. This can be obtained through bronchoscopy guided transbronchial biopsy, CT-guided biopsy, or surgical biopsy [10]. The latter is performed if the results of these procedures are inconclusive and if a mediastinal biopsy is warranted. In these cases, cervical mediastinoscopy, video-assisted thoracic surgery (VATS), or other minimally invasive methods are performed [11]. Endobronchial ultrasonography (US), a significant advancement in bronchial imaging, is commonly used for guidance in fine needle aspiration biopsy. This minimally invasive procedure is effective in diagnosing pulmonary sarcoidosis in comparison with other modes of imaging and procedures [12]. Additional studies are pulmonary functions tests and laboratory studies including calcium levels in serum and urine which are obtained before treatment and a month after completion.

Anergy
  • […] environmental agents Increased risk with some HLA genotypes Increase in pulmonary T cell CD4:CD8 ratio Increase in T cell derived cytokines IL-2 and IFN-gamma Increase in other cytokines (IL-8, TNF, others) in microenvironment Clinical features Commonly anergy[pathologyoutlines.com]
  • […] lung function tests show restrictive, less commonly, obstructive disease; ocular disease occurs in 25%–redness, photophobia, blurred vision; other findings: erythema nodosum, lymphadenopathy, hepato- and/or splenomegaly Immunology Cellular immunity–anergy[medical-dictionary.thefreedictionary.com]
Pulmonary Infiltrate
  • In stage 3 sarcoidosis, pulmonary infiltrates without hilar lymphadenopathy occur. Definitive diagnosis requires a histopathological specimen, which might be difficult to obtain by transbronchial biopsy.[ncbi.nlm.nih.gov]
  • The patient was a 41-year-old man presenting with stage I pulmonary sarcoidosis (hilar adenopathy), which had progressed to stage II (pulmonary infiltrates) 19 months later. FDG-PET was performed at 19, 29 and 33 months after presentation.[ncbi.nlm.nih.gov]
  • For patients who do have impaired lung function with pulmonary infiltrates, adrenal corticosteroids are prescribed, often for an extended period of time. Patients are encouraged to keep appointments for follow-up medical evaluations.[medical-dictionary.thefreedictionary.com]
  • The main tools your doctor will use to diagnose sarcoidosis include: Chest X-rays to look for cloudiness (pulmonary infiltrates) or swollen lymph nodes ( lymphadenopathy ).[webmd.com]
Atelectasis
  • […] cysts · Associated with TB (13%) · Pleural effusion (2%) · Usually exudate with lymphocytic predominance · Cavitation of nodules ( · Fungus ball formation in chronic sarcoid cavities (usually TB) · Focal pleural thickening · Bronchostenosis with lobar atelectasis[learningradiology.com]
  • […] microenvironment Clinical features Commonly anergy to skin test antigens, polyclonal hypergammaglobulinemia Presents as perihilar node involvement, diffuse pulmonary disease, pulmonary interstitial fibrosis, localized bronchial stenosis, distal bronchiectasis and atelectasis[pathologyoutlines.com]
Bilateral Hilar Adenopathy
  • hilar adenopathy, fever, erythema nodosum and arthralgia · Intrathoracic disease (90%) · Adenopathy alone (43%)-Stage 1 · Intrathoracic adenopathy in 80% · Location · Bilateral hilar and (R) paratracheal · Most common (75-90%) · “1-2-3 sign”, “Pawn-broker[learningradiology.com]
X-Ray Abnormal
  • Stages of sarcoidosis describe the chest x-ray abnormality: Stage I disease has only enlarged hilar and mediastinal lymph nodes (these gland sit outside the lungs); Stage II disease has enlarged lymph glands as seen in Stage I disease, but it also has[sarcoid-network.org]
Chest X-Ray Abnormal
  • Stages of sarcoidosis describe the chest x-ray abnormality: Stage I disease has only enlarged hilar and mediastinal lymph nodes (these gland sit outside the lungs); Stage II disease has enlarged lymph glands as seen in Stage I disease, but it also has[sarcoid-network.org]

Treatment

Treatment depends on the clinical picture and whether patients tolerate corticosteroids. Furthermore, physician expertise and patient preference contribute to the decision-making process in regimen selection. Consultation with specialists can guide treatment planning as well.

Oral corticosteroids

Asymptomatic and stable patients do not require treatment. However, symptomatic stage 1 with progressive adenopathy is treated with oral corticosteroids. Furthermore, patients diagnosed with stage 2 to 4 are treated with oral corticosteroids. Corticosteroid therapy is associated with improvement in symptoms, chest X-ray findings, and spirometry. However, it is not has been established if it slows progression of the disease process [13]. 

Precautions should be employed with corticosteroids due to the association of this class of drugs with osteoporosis. Furthermore, since pulmonary sarcoidosis tends to produce hypercalcemia, calcium and vitamin supplements should be used cautiously. Finally, serum calcium levels and 24 hours urinary calcium are obtained at baseline and one month after treatment completion [14].

Second-line

Drugs such as methotrexate, azathioprine, or hydroxychloroquine may be used as an alternative or adjunct treatment to corticosteroids. Furthermore, therapies in the experimental trials may offer promise for the future. 

Lung transplant can be considered in patients with end-stage lung disease, which is characterized by reduced lung volume, flow rate, and diffusing capacity of the lung for carbon monoxide (DLCO). This serious disease state is accompanied by severe symptoms. Of note, sarcoidosis accounts for 2.6% of lung transplants [15]. Patients exhibiting oxygen saturation less than 89% will require oxygen supplementation. Rarely, acute respiratory failure develops and requires mechanical ventilation. These patients will need intravenous corticosteroids until they can switch to oral intake.

Prognosis

The mortality rate is under 5% for patients not receiving treatment. In fact, most patients do not need treatment and will spontaneously recover. While respiratory impairment develops in 15% to 20% of patients, remission is likely to occur. However, certain patients experience chronic debilitating manifestations. An advanced stage on initial chest radiography is suggestive of poor prognosis. Adverse outcomes are also correlated to factors such as extrapulmonary involvement and presence of pulmonary hypertension.

One study investigated the complications of stage IV sarcoidosis during a 7-year follow up, in which 30% of patients were associated with pulmonary hypertension and 12% required chronic oxygen therapy. 11% of deaths were secondary to refractory pulmonary hypertension, respiratory failure, and cardiac sarcoidosis. Furthermore, respiratory causes accounted for 75% of deaths. Also, the study concluded that the 10-year survival rate was 84% [7].

Mortality in the United States increased in the late 1980s and the following two decades. This has been particularly true for black females over 55 [8]. Additionally, a majority of the fatalities were attributed to sarcoidosis itself [8].

Etiology

The cause of sarcoidosis is not established. It is likely that the etiology is multifactorial with genetics and environmental interplay [2]. It is not autoimmune nor malignant in origin.

Epidemiology

The incidence of sarcoidosis is approximately 6 people per 100,000 population [3]. Regarding race, black people are at higher risk in the United States. Additionally, individuals with Scandinavian exhibit a greater incidence. With regards to manifestations, black people are more likely to have chronic uveitis [3], skin involvement (excluding erythema nodosum), and sarcoidosis in the eye, liver, bone marrow and lymph nodes outside the chest [4]. Lupus pernio is more frequently observed in Puerto Ricans while erythema nodosum is more common in Europeans [3]. Furthermore, ocular and cardiac involvement are more often seen in Japan.

There are gender preferences for different clinical manifestations. For example, men tend to have hypercalcemia while women are at risk of developing erythema nodosum, eye, and neurological sarcoidosis. Overall, more than 90% of sarcoidosis patients exhibit pulmonary involvement. Of interest, positive family history demonstrates increased risk [5]. 

Sex distribution
Age distribution

Pathophysiology

A key radiographic feature of sarcoidosis is the non-caseating granuloma with giant cells. CD4 lymphocytes are observed throughout the granuloma while CD8 lymphocytes are found at the periphery [6]. This distribution indicates that the formation of granulomas occurs secondary to T-cell-mediated immune response. Hence CD4 lymphocytes accumulate and IL-12, IL-15 and other immunomodulators are secreted to form and maintain granuloma. Note that the initial phase of pulmonary sarcoidosis presents as interstitial disease while the later profound disease is fibrotic. 

Prevention

Annual influenza vaccines are recommended. Additionally, pneumococcal vaccinations are recommended according to guidelines. Smoking cessation is strongly advised. 

Summary

Sarcoidosis is an idiopathic, multisystem inflammatory disease characterized by noncaseating granulomatous formations. This disease is described as an exaggerated immune reaction to an unknown antigen [1] as no organism has been associated with sarcoidosis. While sarcoidosis can affect various organs, more than 90% of patients manifest pulmonary disease. The etiology is not clear but is likely multifactorial. 

Pulmonary sarcoidosis either spontaneously regresses, or it progresses into a chronic debilitating disease. Most patients will recover while the remainder will develop pulmonary fibrosis and likely complications. Furthermore, pulmonary sarcoidosis is classified into four main stages according to the initial chest radiograph. Earlier stages are associated with higher remission rates.

Diagnosis is determined by a detailed history and physical exam in addition to imaging and tissue biopsy. To obtain the latter, the procedure of choice depends on the sites of involvement, the clinical picture, and other factors. With regards to treatment, asymptomatic patients with benign disease do not require any therapy. However, those with symptoms and later stages are treated with oral corticosteroids, second line agents, or both.

Patient Information

Sarcoidosis is an inflammatory disease that can affect many organs. In more than 90% of patients with sarcoidosis, there is involvement of the lungs. This is a condition called pulmonary sarcoidosis. The cause of this disease is not known, but it is very likely that there are environmental and genetic factors that play a role in the disease.

Sarcoidosis affects ages between 20 and 40 years old. It is more commonly found in women than men. Also, in African Americans, the disease is usually more serious. Additionally, it observed more in Northern Europeans, particularly Scandinavians.

Most patients with pulmonary sarcoidosis have no symptoms and will heal on their own without any medication. Some people will experience a progression of the disease. They will complain about fatigue, weight loss, fever, and swollen lymph nodes. There are also pulmonary symptoms such as a dry cough, chest discomfort, and shortness of breath.

Diagnosis is established in part through a detailed history and physical exam. Also, it is very important to perform imaging and tests. The doctor will obtain a chest X-ray, which will show specific collections of cells. Since other conditions can have the same feature, the doctor may have to take a biopsy, which is a sample of the affected tissue.

There are different ways to obtain a biopsy. One method is to use bronchoscopy, which is a flexible tube that goes into the throat and through the lungs. This allows for examination of the tissue and removal of some tissue. This tissue will be sent to the laboratory for analysis. Note that there are other methods that can be used depending on the location of the tissue and if certain lymph nodes in the chest are affected. The doctor will also test for lung function in case the patient is having difficulty with breathing

Treatment is usually for patients with symptoms. The main treatment is corticosteroids by mouth. Since these have side effects such as osteoporosis, the doctor will monitor this. Also, since pulmonary sarcoidosis usually increases the calcium in the blood, patients are advised not to take calcium or vitamin D supplements. There are other medications available if patients cannot tolerate corticosteroids. In rare cases, patients may need a lung transplant. Patients are advised to update their immunizations such as influenza and pneumococcal vaccines. Smoking cessation is also strongly urged.

References

Article

  1. Ten Berge B, Kleinjan A, Muskens F, et al. Evidence for local dendritic cell activation in pulmonary sarcoidosis. Respiratory Research. 2012; 13:33.
  2. Sverrild A, Backer V, Kyvik KO, et al. Heredity in sarcoidosis: a registry-based twin study. Thorax. 2008; 63(10):894-6. 
  3. American Thoracic Society. Statement on sarcoidosis. American Journal of Respiratory and Critical Care Medicine. 1999;160(2):736-755.
  4. Baughman RP, Teirstein AS, Judson MA, et al. Clinical characteristics of patients in a case control study of sarcoidosis. American Journal of Respiratory and Critical Care Medicine. 2001; 164(10 part 1):1885-1889.
  5. Rybicki BA, Iannuzzi MC, Frederick MM, et al. Familial aggregation of sarcoidosis: a case-control etiologic study of sarcoidosis (ACCESS). American Journal of Respiratory and Critical Care Medicine. 2001; 164(11): 2085-2091.
  6. Kojima K, Maruyama K, Inaba T, et al. The CD4/CD8 ratio in vitreous fluid is of high diagnostic value in sarcoidosis. Ophthalmology. 2012;119(11):2386-92.
  7. Nardi A, Brillet PY, Letoumelin P, et al. Stage IV sarcoidosis: comparison of survival with the general population and causes of death. European Respiratory Journal. 2011,38(6):1368-73.
  8. Swigris JJ, Olson AL, Huie TJ, et al. Sarcoidosis-related mortality in the United States from 1988 to 2007. American Journal of Respiratory and Critical Care Medicine. 2011; 183(11): 1524-30.
  9. Costabel U. Sarcoidosis: clinical update. European respiratory Journal. Supplement . 2001; 32(18):56s–68s.
  10. Trisolini R, Lazzari Agli L, Cancellieri A, et al. Transbronchial needle aspiration improves the diagnostic yield of bronchoscopy in sarcoidosis. Sarcoidosis, Vasculitis, and Diffuse Lung Diseases. 2004; 21(2):147–151.
  11. Zwischenberger JB, Savage C, Alpard SK, et al. Mediastinal transthoracic needle and core lymph node biopsy: should it replace mediastinoscopy? Chest. 2002; 121(4):1165–1170.
  12. Silvestri GA. The mounting evidence for endobronchial ultrasound. Chest. 2009; 136(2):327–328.
  13. Paramothayan NS, Lasserson TJ, Jones P. Corticosteroids for pulmonary sarcoidosis. Cochrane Database of Systematic Reviews. 200; (2):CD001114.
  14. Yeap SS, Hosking DJ. Management of corticosteroid-induced osteoporosis. Rheumatology. 2002; 41(10):1088-1094.
  15. Trulock EP, Edwards LB, Taylor DO, et al. The Registry of the International Society for Heart and Lung Transplantation: twenty-first official adult lung and heart-lung transplant report - 2004. Journal of Heart and Lung Transplant. 2004; 23(7):804-815.

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2019-07-11 21:03