Pneumocystis carinii (disease of the lungs)

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OVERVIEW

由孢子丝菌引起的肺部慢性真菌病
主要表现为发热、咳嗽、咳痰等，严重时可出现呼吸衰竭
由申克氏孢子丝菌的孢子经呼吸道侵入肺部所致
以药物治疗为主

Definition.

Pulmonary sporotrichosis is a chronic fungal disease of the lungs caused by Sporothrix schenckii, one of the common deep fungal diseases [1].

Sporothrix consists of many species that are widely distributed in nature, especially in tropical and subtropical regions such as Brazil, India, and Mexico. However, the most common cause of human infections is Schenk’s sporotrichum.

Sporotrichosis is usually limited to skin and lymph node infections and is mostly subacute or chronic, but occasionally it can involve other parts of the body, such as lungs, bones and joints, etc., and mainly occurs in patients with impaired immune function [1].

Types

Two major categories are included: primary and disseminated [2-3].

Primary Pneumocystis carinii

According to different pathogenetic features, it can be subdivided into 3 lesion types.

支气管肺炎型

The onset of the disease is acute, and the clinical manifestations are similar to those of acute bacterial pneumonia, such as fever, cough, sputum, fatigue, chest discomfort and pain.

慢性空洞型

Most of them are caused by bronchopneumonia-type lesions that cannot be cured for a long time, and the nodular lesions in the lungs are fused, softened, and necrotic, and when the necrotic material breaks into the bronchial tubes, a thin-walled cavity is formed locally.

淋巴结肿大型

The main lesions are located in the hilar or mediastinal lymph nodes, and there are often no obvious clinical symptoms in the early stage, but the hilar or mediastinal shadows are found to be enlarged by chance during the physical examination or chest imaging for other reasons. In some cases, the enlarged lymph nodes may compress the bronchial tubes, leading to obstructive lung lesions.

Disseminated Pneumocystis carinii

Most often occurs in immunosuppressed patients, such as diabetes mellitus, AIDS, neoplasms, and long-term use of adrenocorticotropic hormones and immunosuppressants.

In addition to extensive and severe lesions in the lungs, it is often accompanied by invasion of the skin, bones, muscles, and important organs such as the liver, kidneys, brain, etc. It manifests itself as an acute onset of the disease, with high fever, severe malaise, anorexia, weight loss, joint stiffness, musculoskeletal pain, jaundice, renal impairment, or systemic failure. Most of them die within a short period of time after the onset of the disease if they are not treated actively.

Incidence

The disease is found all over the world, but it is common in the northeast of China, mostly among farmers, forestry workers, miners, paper workers, and gardeners. It is more common in males than females, and is more common in young adults (<30 years old) [1-3].

Etiology

Causes

Pneumocystis carinii is caused by direct inhalation of the spores of the pathogenic bacteria, and rarely by hematogenous dissemination [2].

Predisposing factors

The disease occurs in tropical, subtropical and temperate regions where air humidity is high and temperatures are favorable, and is most common in field workers, miners, flower growers, gardeners and paper mill workers [2-3].

Most patients have underlying diseases (e.g., diabetes mellitus, AIDS), or are addicted to smoking and alcohol, or have immunocompromised status, such as post-transplantation patients, long-term application of adrenocorticotropic hormones (e.g., prednisone) and immunosuppressants (e.g., cyclophosphamide, azathioprine) [4].

Pathogenesis

Whether the pathogenic bacteria cause disease after contact with the human body and the clinical type of manifestation mainly depend on the virulence of the pathogenic bacteria and the immune status of the host [5].

Symptoms

Clinical manifestations are nonspecific, resembling acute pneumonia or bronchitis with fever, cough and malaise [5-7].

Main symptoms

Fever

Low-grade fever of varying degrees, with body temperature rarely exceeding 38.5°C. For milder cases or those with higher body mass, fever may be present. For milder or weaker people, the fever may not be obvious or even absent.

Cough and sputum

Cough can be characterized by irritating dry cough or accompanied by coughing up yellow sputum. In severe cases, the cough is persistent and severe, which may affect sleep.

Chest tightness

Patients do not have obvious symptoms of chest tightness in the early stage, with the progression of the infection or localized enlarged lymph nodes compressing the bronchial tubes, chest tightness, shortness of breath and decreased endurance of activities may gradually appear in the later stage.

Other

畏寒或寒战

It is a common accompanying symptom of fever.

胸痛

It can be caused by localized lung inflammation involving the pleura, and severe coughing, or deep breathing can aggravate the symptoms of chest pain.

疲倦乏力、食欲减退

It is mostly associated with fever, infection, and other systemic states.

其他肺外表现

For patients with combined skin manifestations, papules, pustules, warty nodules, infiltrative plaques, abscesses, ulcers, etc., often on the face, the backs of the hands, and both upper extremities, the neck, the trunk, and the lower extremities.

Complications

Severe cases can lead to respiratory failure and infectious shock. These conditions are often indicative of a critical condition.

Respiratory failure

Patients mostly show respiratory distress, accompanied by agitation, lips and lips bruises and other signs of hypoxia, and in severe cases, neuropsychiatric symptoms, such as lethargy, delirium, coma and so on.

Infectious shock

If the patient is not treated in time, irritability, pallor, cold and wet extremities, and decreased urine output may occur in the later stage. With the progress of the disease, there may be confusion, shallow breathing, low heart sound, thin and rapid pulse, and decrease in blood pressure. In the late stage, systemic organ failure and life-threatening conditions may occur.

Consultation

Department of Medicine

Respiratory Medicine

If you have respiratory symptoms such as fever, cough, sputum, chest tightness, or difficulty breathing, consult the Department of Respiratory Medicine or the Department of Respiratory and Critical Care Medicine.

Preparation

How to get to the doctor: registration, preparation of documents, FAQs

Tips for the doctor

Wear loose-fitting clothes to facilitate medical checkups and examinations.

Preparation Checklist

症状清单

Pay particular attention to the time of onset of symptoms, special manifestations, etc.

  • Have you had a fever recently? What is the highest temperature? Is the fever accompanied by chills?
  • Are there any respiratory symptoms such as cough, sputum, chest tightness, shortness of breath, dyspnea, etc.?
  • Is the cough worse during the day or at night?
  • What color is the sputum? Does it have a foul odor?
  • Are there factors that aggravate or alleviate chest tightness or shortness of breath, such as activity or position?
  • Are there symptoms of discomfort in other areas?
  • How long have these symptoms lasted?
    • 病史清单
  • What kind of work do you normally do? What is the work environment?
  • Any recent history of trauma?
  • Are there any chronic underlying diseases, such as diabetes, chronic kidney disease, rheumatologic diseases, AIDS, tumors, etc.?
  • What are your oral medications?
    • 检查清单

    Test results in the last six months, which can be carried to the doctor

  • Laboratory tests: blood count, full biochemistry, coagulation function, four infections, T/B cell subpopulation count, etc;
  • Chest imaging tests: e.g. chest X-ray, chest CT (it is recommended to bring the imaging films);
    • 用药清单

    Medication use in the last 3 months, including those related to the underlying disease, if available in boxes or packages, carry with you to the doctor’s office

  • Adrenocorticotropic hormones: including oral hormones such as prednisone, dexamethasone, methylprednisone, and intravenous hormones such as methylprednisolone.
  • Immunosuppressants: e.g. cyclophosphamide, azathioprine, hydroxychloroquine, etc.
  • Antipyretic drugs: e.g., ibuprofen, acetaminophen.
  • Recently used anti-infective drugs: e.g., cefdinir, levofloxacin, itraconazole.
  • Cough expectorants: e.g., Ambroxol hydrochloride oral solution, acetylcysteine effervescent tablets, etc.

    • Diagnosis

    Diagnosis is based on

    medical history

  • The patient has a history of exposure to endemic areas or has a long history of employment in forestry, farmers, miners, or paper making.
  • Pre-existing chronic underlying diseases, tobacco and alcohol addiction or immunocompromised state, application of immunosuppressants or hormonal drugs.

    • Clinical manifestations

    症状

    Patients have fever, cough, sputum, fatigue, shortness of breath and other symptoms.

    体征

    It may be characterized by shortness of breath, and wet rales can be heard in the lungs. In severe cases of hypoxia, cyanosis of the lips and mouth and impaired consciousness may occur.

    Pathogenetic examination

    直接镜检

    Take sputum, pus or biopsy tissue direct smear, for Gram stain or PAS staining, high power microscope can see positive staining oval or spindle-shaped vesicles.

    真菌培养
  • Fungal culture is the gold standard for the diagnosis of sporotrichosis.
  • Observation of colony growth and microscopic structure, consistent with the characteristics of sporotrichosis can confirm the diagnosis.
    • 分子生物学检测

    Sputum, pus or necrotic tissue smears are sent to Metagenomic next generation sequencing (mNGS), which can directly extract Schenk’s sporotrichous filamentous bacterial DNA to do high-throughput sequencing and improve the positive rate.

    免疫学检查
  • Intradermal injection of 0.1 ml of 1:1000 bacterial vaccine, the appearance of nodules in 24-48h is considered positive.
  • Serum precipitin and agglutinin were positive (titer increased), and complement binding test was positive.
    • 组织病理学检查
  • The characteristic histopathological change of sporotrichosis is mixed inflammatory cell granulomatous change, which can be seen in the typical “three-zone lesion”: the central “septic zone”, the outer “tuberculosis-like zone”, and the outermost “syphilis-like zone”.
  • Histopathologic examination is important for diagnosis, and identification of pathogens in biopsy specimens can also confirm the diagnosis.

    • Imaging

  • These include chest radiographs and chest CT.
  • Imaging is not specific, and may show patchy or solid shadows in the lungs with/without fibrotic nodular shadows or cavity formation, and with/without enlargement of hilar, tracheal and bronchial lymph nodes.

    • Bronchoscopy

  • Bronchoscopy may be considered if pathogenetic diagnosis is difficult.
  • Acute and chronic inflammation of the bronchial tubes can be seen microscopically. Bronchoalveolar lavage can be performed in the bronchial subsegment near the lesion site, and the lavage fluid can be sent for pathogenetic examination to assist in the diagnosis.
  • At the same time, microscopic lesions can be considered microscopic clamp or transbronchial lung tissue biopsy, and the tissue is sent to pathology.

    • Pathologic examination

    Pathologic examination reveals typical tuberculosis-like structures with negative antacid staining, and cigar-like vesicles and stellate vesicles have diagnostic value.

    Diagnostic criteria

    Based on epidemiologic history, clinical manifestations, chest imaging, fungal culture and histopathologic examination, the diagnosis can be clear [8-9].

    Differential diagnosis

    Pulmonary nodular disease

  • Similarities: both may present with fever, cough, sputum, dyspnea and other symptoms.
  • Differences:
    • 肺结节病患者的胸部CT往往为纵隔及双肺门对称性淋巴结肿大，血清血管紧张素转化酶（ACE）水平明显升高，肺泡灌洗液的病原学检测阴性。肺组织病理提示非干酪性坏死性上皮样细胞性肉芽肿。
    肺孢子丝菌病患者的胸部CT中，纵隔或肺门淋巴结肿大仅为一侧，血清血管紧张素转化酶（ACE）水平阴性，肺泡灌洗液中可检测到申氏孢子丝菌。病理检查如见雪茄样小体及星状小体有诊断价值。

    Lung cancer

  • Similarities: both may present with cough and sputum, and some patients may be accompanied by fever and dyspnea.
  • Differences:
    • 肺癌患者多为中年起病，存在吸烟史，可伴有咯血症状。胸部影像学表现为肺部肿块影，相关肿瘤标志物水平可升高，肺组织病原学检查为阴性，病理活检可找到肿瘤细胞。
    而肺孢子丝菌病以青壮年多见，患者的血清肿瘤标志物往往阴性，病原学检查提示申克孢子丝菌阳性，组织病理发现典型结核样结构而抗酸染色阴性，可见雪茄样小体及星状小体。

    Tuberculosis

  • Similarities: both may present with cough, sputum and fever.
  • Differences:
    • 部分患者存在结核接触史。痰培养或肺泡灌洗液中可找到结核杆菌。组织病理可见坏死性干酪样肉芽肿。
    肺孢子丝菌病患者往往具备流行病学史，肺泡灌洗液中可检测到申氏孢子丝菌。病理检查如见雪茄样小体及星状小体有诊断价值。

    Other chronic fungal infections

  • Similarities: cough, sputum, fever.
  • Difference: mainly rely on pathogenetic testing, pathology results to confirm the diagnosis.

    • Treatment

    Aim of treatment: improve lung ventilation function, eradicate infection, prevent complications, improve quality of life, prolong survival time.

    Therapeutic principles: the choice of treatment mainly depends on the clinical phenotype of the disease, the immune status of the host and the species of sporotrichosis, but the optimal treatment for pulmonary sporotrichosis is not clear [8-9].

    Pharmacologic therapy

    Pharmacotherapy is the mainstay of treatment for Pneumocystis carinii.

    Commonly used drugs include itraconazole and amphotericin B. In addition, 10% potassium iodide solution, which is commonly used in cutaneous sporotrichosis, is also used in pulmonary sporotrichosis, but the efficacy of the treatment is not exact.

    Itraconazole

  • For non-severe pulmonary sporotrichosis, guidelines prefer itraconazole as first-line drug therapy. The duration of therapy is at least 1 year.
  • Lifelong oral itraconazole therapy is required if the immune status of patients with AIDS and other conditions cannot be restored [10].
  • Adverse reactions need to be guarded against during administration, mainly including headache, rash, gastrointestinal symptoms such as nausea, diarrhea, abdominal pain, dyspepsia, and flatulence. Also, liver function should be monitored.

    • Amphotericin B

  • For critically ill or life-threatening pulmonary sporotrichosis, current guidelines prefer early application of injectable amphotericin B in combination with oral itraconazole for a total treatment course of up to 1 year.
  • Amphotericin B has significant drug side effects. Chills, fever, and hypotension are likely to occur during the first infusion of the drug. At the same time, the drug may cause headache, gastrointestinal symptoms such as nausea, vomiting, liver and kidney function impairment and thrombocytopenia, hypokalemia. It should be monitored during application.

    • Surgical treatment

    Surgical treatment of the lungs is only used for those who have imaging manifestations of limited lesions or advanced manifestations of cavitation-like lung lesions [6, 11]. There is no consensus on whether surgery is recommended in the early stages.

    Prognosis

    Cure

    Pneumocystis carinii has a high mortality rate and poor clinical prognosis.

    According to foreign literature, about 42.9% of patients eventually die from related complications [4], especially in immunosuppressed patients, especially those with AIDS, where the disease may spread and lead to death.

    Prognostic factors

    Prognosis is related to the presence of cavitary lesions and host immune status [5].

    Presence of cavitary lesions

    In this subset of patients with the presence of cavitary lung lesions, drug therapy tends to be ineffective, and considerations may be related to the low bioavailability and plasma concentration of oral antifungal drugs (especially itraconazole), insufficient penetration of antifungal drugs into the oral cavity, and fibrotic peripheral areas in advanced disease further limiting the drug’s ability to reach the diseased tissue.

    Host immune status

    In patients with diabetes mellitus alone, with aggressive correction of blood glucose, their drug therapy is more effective and has a favorable clinical prognosis. In hosts that are immunosuppressed, drug therapy is less effective, with longer treatment cycles, poorer prognosis, and higher mortality.

    Daily

    Daily management

  • Pay attention to rest, avoid trauma, cold, cold, labor.
  • Avoid smoking and alcohol.
  • Take appropriate physical exercise.
  • Strengthen nutrition, light and easy-to-digest diet, increase protein intake.
  • Take medication regularly during treatment, do not reduce or stop the medication by yourself.

    • Follow-up examination

  • Chest X-ray or CT should be repeated 1-3 months after discharge from the hospital to ascertain the absorption and dissipation of chest lesions.
  • During the period of medication, monitor the blood routine, liver and kidney functions, and be alert to the side effects of the drugs.

    • Prevention

  • Contaminated decaying materials and weeds should be burned in the epidemic area to eliminate the source of infection and cut off the transmission pathway as much as possible.
  • People engaged in paper making, agriculture and animal husbandry should do personal protection.
  • Actively treat relevant underlying diseases, such as diabetes and AIDS, and strictly review and assess the condition regularly;
  • Exercise more to enhance their immunity and increase protein intake.
    • 参考文献
    [1]
    Sizar O, Talati R. Sporotrichosis[M]. BTI – StatPearls，2022.
    [2]
    林果为，王吉耀，葛均波. 实用内科学[M]. 15版. 北京：人民卫生出版社，2017.
    [3]
    张学军，郑捷.皮肤性病学[M]. 9版，北京：人民卫生出版社，2018.
    [4]
    Orofino-Costa R, Freitas DFS, Bernardes-Engemann AR, et al. Human sporotrichosis: recommendations from the Brazilian Society of Dermatology for the clinical, diagnostic and therapeutic management[J]. An Bras Dermatol, 2022, 97(6):757-777.
    [5]
    Fichman V, Mota-Damasceno CG, Procopio-Azevedo AC, et al. Pulmonary Sporotrichosis Caused by Sporothrix brasiliensis: A 22-Year, Single-Center, Retrospective Cohort Study[J]. J Fungi (Basel), 2022, 8(5).
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    Aung AK, Teh BM, McGrath C,et al. Pulmonary sporotrichosis: case series and systematic analysis of literature on clinico-radiological patterns and management outcomes[J]. Med Mycol,2013,51(5):534-44.
    [7]
    Rojas FD, Fernandez MS, Lucchelli JM, et al. Cavitary Pulmonary Sporotrichosis: Case Report and Literature Review[J]. Mycopathologia, 2017,182(11-12):1119-23.
    [8]
    Limper AH, Knox KS, Sarosi GA, et al. American Thoracic Society Fungal Working Group. An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients[J]. Am J Respir Crit Care Med, 2011,183(1): 96–128.
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    Kauffman CA, Bustamante B, Chapman SW, et al. Infectious Diseases Society of America. Clinical practice guidelines for the management of sporotrichosis: 2007 update by the Infectious Diseases Society of America[J]. Clin Infect Dis, 2007,45(10): 1255–1265.
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    王宇明,李梦东.实用传染病学[M].4版. 北京:人民卫生出版社,2017.
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    Orofino-Costa R, Unterstell N, Carlos Gripp A, et al. Pulmonary cavitation and skin lesions mimicking tuberculosis in a HIV negative patient caused by Sporothrix brasiliensis[J]. Med Mycol Case Rep, 2013,2:65–71.