A Guide to Diagnosing Pyrexia of Unknown Origin (PUO)

What is Pyrexia of unknown origin PUO ? 

The term Pyrexia of unknown origin (PUO), also referred to as "Fever of unknown origin (FUO)", refers to a collection of numerous unrelated medical diseases that have one thing in common: a prolonged, unexplained fever that persists after a PUO Panel test. Despite years of medical practice and the advancement of new technologies, treatment of this ailment is still challenging for doctors today. Given how many different illnesses can manifest in this way and how differently they can do so, the source of a patient's PUO may be difficult to recognise. 

Types of Pyrexia of unknown origin PUO / fever of unknown origin (FUO) 

The classification of PUO is based on its traits, weaknesses, and time of evaluation. The kinds of PUO are as follows: 

• Classical PUO disease 

• Nosocomial PUO disease 

• Immune deficient or Neutropenic PUO disease 

• HIV-associated PUO disease 

1. Classical PUO: Infections, malignancies, collagen disorders, and vascular diseases are the causes of a traditional type of PUO. The patient has had a 38.3 C temperature for longer than 3 weeks. 

2. Nosocomial PUO: Nosocomial Pyrexia of undetermined origin is a fever brought on by hospitalisation. The patient is typically admitted for another ailment but soon develops a PUO fever that is hard to diagnose. Nosocomial PUO can be caused by sinusitis, septic thrombophlebitis, pulmonary embolism, drug-induced Pyrexia,  enterocolitis, or drug-induced Pyrexia. 

3. Immune Deficiency PUO: People who have weakened immune systems are more susceptible to infection, which might result in Pyrexia of unclear origin. Bacterial infection, aspergillosis, candidiasis, or the herpes virus can all cause it. 

What are the causes of Pyrexia of unknown origin (PUO) ? 

PUO causes are mostly differentiated into 4 groups. 

• Infective  

• Non-infectious Inflammatory diseases 

• Neoplastic 

• Miscellaneous 

1. Infective: It makes up 17-35% of cases and is brought on by viral, fungal, parasitic, and bacterial (both specific and non-specific) organisms. Abdominal or pelvic abscesses and tuberculosis (especially in extrapulmonary locales) are the most common infectious diseases linked to PUO PUO FUO Intra-abdominal abscesses are linked to diverticulitis, cancer, trauma, and punctured hollow viscera (like those observed in appendicitis). Potential causes of PUO/FUO include infections such as sinusitis, osteomyelitis, subacute bacterial endocarditis, and tooth abscesses. 

2. Non-infectious inflammatory diseases: 24-36% of cases are made up of them. Autoimmune illnesses are frequently non-infectious inflammatory diseases. Currently, the two most common autoimmune causes of PUO or FUO are adult Still's disease and temporal arteritis. The most frequent association between PUO/FUO and older patients with multisystem inflammatory illnesses is polymyalgia rheumatica and temporal arteritis. 

3. Neoplastic: 10-20% of cases are neoplastic. Patients with PUO  or FUO  frequently have cancers that might be difficult to identify, such as metastatic tumours, chronic leukaemia, lymphoma, and renal cell carcinoma. 

Pyrexia of unknown origin- PUO in children 

Puo in children is a common problem that usually ranges between 10 and 21 days. After initial outpatient or inpatient workup, the PUO/FUO in children is characterised by an elevation in body temperature of 38.3 °C that persists for at least ten days without having a clear reason. 

Children's connective tissue disorders, infections, and oncologic illnesses are the main causes of PUO or FUO. Paediatricians find it difficult to diagnose PUO children because many of them resolve on their own without a diagnosis. 

Pyrexia of unknown origin- PUO symptoms 

PUO  is a clinical illness marked by a persistent, unexplained temperature of 101°F (38.3°C) or higher for at least three weeks without a conclusive diagnosis despite a thorough medical examination. Because a wide range of probable reasons must be ruled out, diagnosing PUO can be difficult. Depending on the underlying reason, PUO symptoms can vary. However, there are some universal characteristics and methods for assessing these symptoms. 

1. Fever: An abnormal fever is the primary sign of PUO. It's crucial to remember that in order to be considered PUO, the temperature must be elevated above 101°F (38.3°C) for a minimum of three weeks. Fatigue: Many people with PUO report feeling extremely weak and tired, which can affect their ability to carry out daily tasks and their quality of life. 

2. Night Sweats: Excessive nighttime perspiration is another typical symptom. Night sweats can cause sleep disruptions and are frequently described as drenching. 

3. Weight Loss: PUO is frequently accompanied by unintended weight loss. Significant and unexplained weight loss like this can raise questions about underlying illnesses. 

4. Pain and discomfort: Patients with PUO may feel a variety of pains, depending on the underlying reason. This could include, among other things, chest pain, abdominal pain, or joint pain. 

Risk factors of Pyrexia of unknown origin (PUO) 

PUO  is a difficult clinical disease characterised by an ongoing, unidentified fever in spite of careful diagnostic scrutiny. Understanding the likelihood of PUO in various people and directing the diagnostic process can benefit from knowing the risk factors linked with the condition. The following are some of the risk factors that can make someone more likely to acquire PUO: 

1. Occupational Exposure: Some jobs can make you more likely to get PUO. If necessary precautions are not taken, those working in animal care facilities, laboratories, and the healthcare industry may be exposed to pathogenic organisms that might cause FUO. Chronic Medical problems: The risk of PUO is higher in people who have pre-existing chronic medical problems such as diabetes, chronic renal disease, or inflammatory illnesses. The body may be more vulnerable to infections and other inflammatory processes as a result of these diseases. 

2. Medication: As a side effect, some drugs might cause fever, which may increase the risk of PUO. Antibiotics, antiepileptic meds, anti-inflammatory drugs, and many more drugs can cause drug-induced fever. 

3. Autoimmune Disorders: Before the underlying autoimmune disease is identified, symptoms of PUO may initially appear in the form of rheumatoid arthritis, systemic lupus erythematosus, or vasculitis. 

4. Prior Surgical Procedures: Recent surgical procedures can occasionally result in infections or inflammatory reactions that present as PUO, especially if they involve prosthetic implants or foreign materials. 

Pyrexia of unknown origin- PUO diagnosis 

Even after thorough assessments, nearly 5 to 15% of patients remain undiagnosed. The goal of the general practitioner's thorough patient history, physical exam, and prescription of laboratory tests is to look for potential diagnostic clues (signs, symptoms, and anomalies that indicate a PUO diagnosis). Before starting a lab diagnostic for PUO  or FUO, the doctor would want to stop the patient from taking any medications that conceal the presence of any diseases or interfere with the clinical findings. 

Pyrexia of unknown origin differential diagnosis 

The differential diagnosis of PUO can be broken down into the following four groups based on aetiology: infections, neoplasms, inflammatory diseases, and miscellaneous. 

1. Infections: Infection causes 33% of cases of FUO. Mild tuberculosis, Q fever, Typhoid fever, Amebiasis, Brain abscess, Cholangitis, Cholelithiasis, Chagas disease, Dengue fever, Diabetic ulcers, Hepatitis A-E, Liver and lung abscesses, Malaria, Pelvic inflammatory disease, HIV, etc. are the most prevalent illnesses that result in FUO. 

2. Neoplasms: Neoplasms make up to 18% of the causes of FUO. Lymphoma, Renal cell carcinoma, Atrial myxoma, Multiple myeloma, Acute myeloid leukaemia, Myeloproliferative diseases, Colon carcinoma, Hepatoma, Systemic mastocytosis, CNC metastases, Pancreatic carcinoma, Liver metastasis, etc. are the most common aetiologies of FUO. 

3. Inflammatory diseases: It accounts for 33% of FUO cases that occur because of rheumatologic and inflammatory conditions such as Adult Still disease, Giant cell/temporal arteritis, Marshall syndrome, Periarteritis nodosa, Pseudogout, Polyarticular gout, Microscopic polyangiitis, Sarcoidosis, Rheumatoid arthritis, Takayasu arteritis, Systemic lupus erythematosus, Gaucher disease, Behcet disease, Kikuchi disease, Felty syndrome, antiphospholipid syndrome. 

4. Miscellaneous: The remaining FUO aetiologies (16%) are categorised as miscellaneous or other and include conditions such as Familial mediterranean fever, Factitious fever, Subacute thyroiditis, Hypothalamic dysfunction, Crohn's disease, drug-induced fevers, Hematomas, Pulmonary emboli, and Deep vein thrombosis. 

What is the treatment for Pyrexia of unknown origin (PUO)  

Most of the time, no therapy other than supportive care should start before a diagnosis is made. Therapeutic trials are not advised. Since PUO has a low fatality rate and early use of antipyretics or antibiotics may postpone diagnosis, this strategy for treating PUO is recommended. The fatality rate of PUO is less than 10% with malignancy accounting for the majority of these deaths. The patient must have the proper counselling in order to ensure that they comprehend the investigation process for PUO. It is crucial to emphasise that mortality is low, especially if a PUO diagnosis cannot be made and there are no "red flag" symptoms, indicators, or tests. 

Conclusion  

We have discussed a medical ailment in this article that is called PUO and is characterised by a persistent, inexplicable fever. With numerous probable causes, including infections, neoplasms, inflammatory disorders, and other illnesses, the diagnosis for PUO is yet to be found. 

To identify the disease it is important to get PUO blood test done. Metropolis Labs provide convenient testing facilities. Book your appointment online or offline and get to know the possible PUO causes.