Introduction

Episodes of generalized sweating, occurring either during the day or night (or both), are a common presenting symptom in primary care. While the cause may be evident after history-taking, often no etiology is immediately apparent. In such cases, clinicians face the challenge of pursuing a thoughtful, cost-effective yet comprehensive diagnostic strategy.

The evaluation of the patient with night sweats or generalized hyperhidrosis is discussed here. The management of benign excessive sweating limited to certain areas of the body (primary focal hyperhidrosis) is discussed separately.

Although hot flashes and flushing are discussed here as they relate to the diagnostic evaluation of night sweats, they are reviewed in greater detail elsewhere.

Definitions

• Excessive Sweating (Hyperhidrosis): Sweating in excess of that needed to control body temperature. It can be primary (idiopathic) or secondary (due to an underlying cause). When sweating is confined to specific areas, it is called primary focal hyperhidrosis.
• Night Sweats: Episodes of generalized sweating during sleep that range from mild diffuse sweating to severe drenching sweats that require changing bedclothes.
• Hot Flashes: A sudden warmth and visible redness in the chest, neck, and face, followed by sweating. Often associated with menopause.
• Flushing: An increase in cutaneous blood flow resulting in warmth and redness of the face or trunk, which may be associated with sweating.

Epidemiology

• In primary care, 24% to 41% of patients report night sweats.
• 2.8% to 16.3% of the general population experience generalized hyperhidrosis.
• Duration of recurrent sweating, especially when lasting over a year, often indicates a benign etiology.

Initial Assessment of All Patients

A comprehensive history and physical exam are crucial in identifying serious underlying causes while avoiding unnecessary testing.

Key Aspects of History

• Characteristics of Sweating: Determine severity, frequency, and timing (night vs. day sweats).
• Fevers: Exclude fever. If present, infection or malignancy becomes more likely.
• Risk Factors for Tuberculosis (TB), HIV, and Bacterial Infections.
• Constitutional Symptoms: Unintentional weight loss, fatigue, and pruritus could suggest malignancy.
• Hormonal Status: For females, assess menopausal status; for males, inquire about androgen deprivation therapy.
• Endocrine Symptoms: Ask about flushing, diarrhea, wheezing, palpitations, or weight loss indicating endocrine disorders (e.g., hyperthyroidism).
• Medication History: Certain drugs (e.g., antidepressants, cholinergic agents) can cause sweating.
• Neurologic History: Assess for spinal cord injury, stroke, or autonomic dysreflexia.

Focused Physical Examination

• General health and nutrition, vital signs, and lymph node examination.
• Examine the thyroid for thyromegaly or nodules.
• Lymphadenopathy, abnormal findings on thyroid exam, or unusual skin changes require further investigation.

Diagnostic Strategy

The next step in diagnosis is based on the clinical history and physical exam. Treatment should not start with empirical antibiotic therapy.

Patients with History and Physical Findings Suggesting a Specific Etiology

• Tuberculosis (TB): Perform TB skin test, chest imaging, and sputum collection.
• Lymphoma: CT or PET scan, biopsy of enlarged lymph nodes, and bone marrow biopsy.
• Tick-Borne Illnesses: Perform blood tests for babesiosis, ehrlichiosis, anaplasmosis, Lyme disease, and malaria.
• Hormone Deficiency: Hormonal treatments for testosterone reduction or menopause are usually diagnosed based on symptoms.
• Medication-Related Sweats: Consider discontinuing suspected medications to evaluate their role in symptoms.

Patients with Unexplained Night Sweats or Generalized Hyperhidrosis

• Initial Tests: TB evaluation, complete blood count (CBC), thyroid-stimulating hormone (TSH), HIV serology, C-reactive protein (CRP), liver function tests, and blood cultures.
• CT or PET Scan: To evaluate for lymphoma, solid tumors, or abscess if initial tests are normal.
• Echocardiogram: To check for culture-negative endocarditis if other studies do not reveal a cause.
• Bone Marrow Biopsy: If no cause is found, particularly if night sweats persist beyond eight weeks.
• Urine Collection: For 5-hydroxyindoleacetic acid (5-HIAA), metanephrine, and catecholamines if symptoms persist without a diagnosis.

Differential Diagnosis

The differential for generalized hyperhidrosis and night sweats includes infection, malignancy, medications, endocrine causes, neurologic disease, and idiopathic hyperhidrosis.

Infections

• Tuberculosis (TB): A common cause of night sweats, especially in extrapulmonary TB.
• HIV: Acute seroconversion or opportunistic infections may cause sweating.
• Bacterial Infections: Endocarditis, osteomyelitis, and pyogenic abscesses may present with night sweats.
• Brucellosis: A zoonotic infection with joint pain, fatigue, and night sweats.
• Malaria: Common in travelers, often presents as night sweats.
• Babesiosis, Ehrlichiosis, and Anaplasmosis: Tick-borne infections that may cause fever and sweats.

Malignancies

• Lymphoma: Particularly associated with night sweats.
• Solid Tumors: Prostate cancer, renal cell cancer, and medullary thyroid carcinoma can also present with night sweats.

Medications

• Antidepressants: Common cause of night sweats, particularly tricyclics, SSRIs, and venlafaxine.
• Cholinergic Agents: Stimulate sweating through muscarinic receptors.
• Hypoglycemic Agents: Patients with diabetes on insulin or oral hypoglycemics may experience nocturnal sweating due to hypoglycemia.
• Estrogen/Androgen Modulating Agents: Medications such as GnRH agonists and aromatase inhibitors may cause hot flashes and sweating.

Endocrine Causes

• Hyperthyroidism: Heat intolerance and increased sweating.
• Pheochromocytoma: Characterized by episodic sweating, headaches, and hypertension.
• Carcinoid Syndrome: Flushing and sweating, commonly with diarrhea and wheezing.
• Insulinoma: May cause night sweats due to nocturnal hypoglycemia.
• Acromegaly: Malodorous hyperhidrosis.

Neurologic Causes

• Autonomic Dysreflexia: Common in high spinal cord injuries, with acute sweating episodes.
• Syringomyelia: Can cause episodic sweating, especially in a post-traumatic context.

Sleep Disorders

• Night sweats are common in obstructive sleep apnea (OSA). Treating the sleep disorder may decrease night sweats.

Other Causes

• Gastroesophageal Reflux, Temporal Arteritis, Sarcoidosis, Chronic Fatigue Syndrome, and Mercury Poisoning can also lead to generalized sweating.