What is the diagnosis and treatment for generalized body itching with no skin markings?

Generalized Body Itching Without Skin Markings

Begin with a systematic laboratory workup including liver function tests, urea and electrolytes, complete blood count, iron studies, fasting glucose, and thyroid-stimulating hormone, while simultaneously initiating treatment with emollients and non-sedating antihistamines. 1, 2

Diagnostic Approach

Essential Initial Laboratory Tests

• Liver function tests to identify hepatic causes, with consideration of bile acids and antimitochondrial antibodies if liver disease is suspected 1, 2
• Urea and electrolytes to evaluate for uremic pruritus from chronic kidney disease 1, 2
• Complete blood count to screen for hematologic disorders including polycythemia vera, lymphoma, and iron deficiency 1, 2
• Iron studies (serum ferritin, iron, total iron-binding capacity) as iron deficiency is a treatable cause 1, 2
• Fasting glucose or A1C only if clinical features suggest diabetes 1, 3
• Thyroid function tests only if additional clinical features suggest endocrinopathy 1

Additional Testing Based on Risk Factors

• HIV and hepatitis A, B, C serology if risk factors are present (travel history, sexual history, injection drug use) 1, 2
• Chest X-ray and abdominal ultrasound if malignancy is suspected based on systemic symptoms, though routine cancer screening is not recommended 1
• Medication review is mandatory to identify drug-induced pruritus 1, 2

Important Caveats

The British Association of Dermatologists explicitly recommends against routine endocrine investigations or extensive malignancy workup unless specific systemic symptoms are present 1. This prevents unnecessary testing while focusing on high-yield investigations.

Treatment Algorithm

First-Line Therapy (Initiate Immediately)

• Emollients with high lipid content applied liberally and frequently to maintain skin barrier function 1, 2, 4
• Non-sedating antihistamines: fexofenadine 180 mg daily or loratadine 10 mg daily 1, 2, 4
• Topical clobetasone butyrate or menthol preparations for symptomatic relief 1, 2, 4
• Topical doxepin (limited to 8 days maximum, covering no more than 10% body surface area, maximum 12g daily) 1, 4

Avoid crotamiton cream, topical capsaicin, and calamine lotion as they are ineffective 1

Second-Line Therapy (If No Response After 2-4 Weeks)

• Combination H1 and H2 antagonists: fexofenadine plus cimetidine 1, 4
• Mildly sedative antihistamines: cetirizine 10 mg daily (preferred over strongly sedating agents) 1, 4

Third-Line Therapy (Refractory Cases)

• SSRIs: paroxetine or fluvoxamine 1, 2, 4
• Mirtazapine (dual benefit for depression and pruritus) 1, 2, 4
• Gabapentin or pregabalin for neuropathic component 1, 4
• Naltrexone (particularly effective for opioid-induced pruritus) 1, 2, 4

Special Considerations for Sedating Antihistamines

Hydroxyzine and other sedating antihistamines should only be used short-term or in palliative settings due to dementia risk with long-term use 1, 4, 5. Despite FDA approval for pruritus management, the British Association of Dermatologists recommends restricting their use 5.

Cause-Specific Treatment

If Hepatic Pruritus Identified

1. Rifampicin (first-line) 2, 4
2. Cholestyramine (second-line) 2, 4
3. Sertraline (third-line) 2, 4
4. Avoid gabapentin in hepatic pruritus specifically 2, 4

If Uremic Pruritus Identified

• Optimize dialysis parameters, normalize calcium-phosphate balance, control parathyroid hormone 2, 4
• BB-UVB phototherapy (Strength of recommendation A - the highest quality evidence) 2, 4
• Avoid cetirizine and long-term sedative antihistamines except in palliative care 2

If Iron Deficiency Identified

• Iron replacement therapy resolves pruritus in iron-deficient patients 1, 2

If Drug-Induced (Opioids)

• Naltrexone is first-choice if opioid cessation is impossible 1, 2, 4
• Methylnaltrexone as alternative 1, 4

If Polycythemia Vera Identified

• Cytoreductive therapy, aspirin, interferon-α, SSRIs, or atenolol 1, 2

If Lymphoma-Associated

• Cimetidine, carbamazepine, gabapentin, or mirtazapine 1, 2
• Oral corticosteroids for incurable lymphoma 1, 2

Elderly Patients

Initiate a 2-week trial of emollients and topical steroids to exclude asteatotic eczema before pursuing extensive workup 1, 2, 4. Moisturizers with high lipid content are preferred in this population 1, 4.

When to Refer

Refer to dermatology if diagnostic uncertainty persists, primary care management fails after 4-8 weeks, or if skin biopsy is needed to confirm small fiber neuropathy 1, 4. Refer to hepatology if significant hepatic impairment is identified 1.

Psychogenic Pruritus Consideration

If all organic causes are excluded after comprehensive workup, consider behavioral interventions, relaxation techniques, cognitive restructuring, and referral to liaison psychiatry 1, 4. Patient support groups can provide additional benefit 1, 4.