What are the potential causes and management options for a patient presenting with hair loss, fatigue, night sweats, and sleeplessness over the past few weeks?

Differential Diagnosis and Management of Hair Loss with Systemic Symptoms

Most Likely Diagnoses to Consider

The constellation of hair loss, fatigue, night sweats, and insomnia over several weeks should prompt immediate evaluation for malignancy (particularly lymphoma), autoimmune disease (especially systemic lupus erythematosus), thyroid dysfunction, and severe nutritional deficiencies. 1, 2

Critical "Red Flag" Conditions

• Malignancy: Night sweats combined with fatigue and hair loss are classic B-symptoms of lymphoma; Hodgkin lymphoma patients show 26% fatigue rates lasting >6 months, with depression correlating moderately (r=0.41) 1
• Systemic Lupus Erythematosus (SLE): Causes both scarring and non-scarring alopecia with systemic symptoms including fatigue and sleep disturbance 3
• Thyroid Disease: Both hyperthyroidism (causing night sweats, insomnia) and hypothyroidism (causing fatigue, hair loss) must be excluded 1

Common Autoimmune and Inflammatory Causes

• Alopecia Areata with Systemic Inflammation: AA shows elevated systemic type 17 and type 2 cytokines (IL-17A, IL-17F, IL-21, IL-23, IL-33, IL-31), with 51% experiencing anxiety and 18% depression 4
• Secondary Syphilis: Presents with patchy "moth-eaten" hair loss and systemic symptoms 5

Immediate Diagnostic Workup

Essential History Elements

• Sleep Pattern Assessment: Distinguish between insomnia (difficulty initiating/maintaining sleep) vs. hypersomnia; screen for obstructive sleep apnea using STOP questionnaire if snoring/observed apneas present 1
• Night Sweats Characterization: Drenching sweats requiring clothing changes suggest lymphoma or infection; mild sweating may indicate thyroid disease or menopause 1
• Hair Loss Pattern: Patchy with exclamation mark hairs indicates alopecia areata; diffuse thinning suggests telogen effluvium or systemic disease; scarring pattern requires urgent dermatology referral 6, 5
• Medication Review: Antidepressants (SSRIs), β-blockers, stimulants, and narcotics all contribute to insomnia and fatigue 1

Physical Examination Priorities

• Dermoscopy of Scalp: Look for yellow dots, exclamation mark hairs, and cadaverized hairs (alopecia areata) vs. uniform thinning (telogen effluvium) 6, 5
• Lymphadenopathy: Palpate cervical, axillary, and inguinal nodes for lymphoma 2
• Peripheral Edema: Suggests cardiac or renal disease contributing to fatigue and nocturia 1
• Thyroid Examination: Assess for goiter, tremor, or bradycardia 1
• Nail Changes: Pitting or ridging occurs in 10% of alopecia areata patients 5

Mandatory Laboratory Tests

First-Tier (Order Immediately):

• Complete Blood Count: Anemia contributes significantly to cancer-related fatigue and may indicate malignancy 1
• Thyroid Function (TSH, Free T4): High TSH with low T4 indicates hypothyroidism; if confirmed, add TPO antibodies 5
• Comprehensive Metabolic Panel: Electrolyte imbalances (sodium, potassium, calcium, magnesium) are reversible causes of fatigue 1
• Erythrocyte Sedimentation Rate/C-Reactive Protein: Elevated in autoimmune disease and malignancy 2

Second-Tier (Based on Clinical Suspicion):

• Serum Ferritin: Iron deficiency is the most common nutritional deficiency worldwide; levels are lower in women with alopecia areata and androgenetic alopecia 5
• Vitamin D Level: 70% of alopecia areata patients have levels <20 ng/mL vs. 25% of controls; lower levels correlate inversely with disease severity 5
• Serum Zinc: Tends to be lower in alopecia areata patients, particularly those with resistant disease >6 months 5
• ANA, Anti-dsDNA: If SLE suspected based on clinical features 5, 3
• RPR/VDRL: If secondary syphilis in differential 5

When to Perform Scalp Biopsy

• Diagnosis remains uncertain after dermoscopy and laboratory testing 6
• Early scarring alopecia suspected (requires urgent intervention) 6
• Diffuse alopecia areata that is diagnostically challenging 5

Management Algorithm by Diagnosis

If Alopecia Areata Confirmed

Limited Patchy Disease (<50% scalp involvement):

• Intralesional corticosteroid injections (triamcinolone acetonide 5-10 mg/mL): First-line treatment with strongest evidence (Strength B, Quality III) 1, 6
• Inject 0.1 mL per site, 1 cm apart, repeat every 4-6 weeks 6

Extensive Patchy Disease (>50% scalp involvement):

• Contact immunotherapy (diphenylcyclopropenone or squaric acid dibutylester): Best-documented treatment though response rates <50% and availability limited 1, 6
• Caution: May cause pigmentary complications in patients with darker skin 6

Adjunctive Measures:

• Vitamin D supplementation: If levels <20 ng/mL, supplement according to general international recommendations for adults 5
• Zinc supplementation: Consider if serum levels low, particularly in resistant disease 5
• Psychological support: 51% experience anxiety, 18% depression; IL-17E and IL-22 levels positively predict depression scores 4

If Sleep Disorder Identified

Obstructive Sleep Apnea:

• Refer to sleep specialist for continuous positive airway pressure therapy 1
• Recommend weight loss and exercise 1

Insomnia (Primary):

• Sleep hygiene education: Regular morning/afternoon exercise, daytime bright light exposure, keep bedroom dark/quiet/comfortable, avoid heavy meals/alcohol/nicotine near bedtime 1
• Cognitive behavioral therapy for insomnia (CBT-I): First-line non-pharmacologic intervention 1
• Avoid excessive time in bed, napping, or "clock watching" 1

Restless Legs Syndrome:

• Check ferritin; if <45-50 ng/mL, supplement iron 1
• Consider dopamine agonists or gabapentin; refer to sleep specialist 1

If Systemic Disease Identified

Hypothyroidism:

• Initiate levothyroxine replacement; hair regrowth typically follows thyroid normalization 5

Nutritional Deficiencies:

• Iron deficiency: Supplement with ferrous sulfate 325 mg daily 5
• Vitamin D deficiency: Supplement to achieve levels >30 ng/mL 5
• Zinc deficiency: Supplement with zinc sulfate 220 mg daily 5

Malignancy:

• Urgent oncology referral for lymphoma workup if B-symptoms present 1

Critical Management Pitfalls to Avoid

• Do not dismiss night sweats as "just menopause" without excluding malignancy, especially with concurrent weight loss or lymphadenopathy 1, 2
• Do not order excessive laboratory tests when alopecia areata is clinically evident on dermoscopy 6, 5
• Do not use systemic corticosteroids or PUVA for alopecia areata due to serious side effects without proven efficacy 1
• Do not assume fatigue is purely psychological; 30-75% of cancer patients have sleep disturbances, and depression is present but distinct from fatigue 1
• Do not overlook medication contributions: Review all medications including over-the-counter, herbal, and supplements for insomnia-inducing effects 1
• Do not ignore the psychological impact: Address quality of life, mood disturbances, and cognitive difficulties that commonly accompany both hair loss and chronic insomnia 1, 4

Follow-Up Strategy

• Reassess at 3 months to evaluate treatment response for alopecia areata 6
• Monitor sleep quality using sleep diaries; fatigue should improve with sleep optimization 1
• Provide written instructions for self-monitoring and when to seek urgent attention (fever, worsening night sweats, weight loss) 6
• Counsel about natural history: 34-50% of alopecia areata patients recover within one year without treatment, but childhood onset and extensive involvement carry poorer prognosis 5