Topical Treatments for Vitiligo

1. Topical Corticosteroids (First-Line)

• Ultrapotent (class I) steroids are required for reliable efficacy; clobetasol propionate is the most studied agent.
• Applied twice daily, often in discontinuous cycles (1 week on / 1 week off for up to 6 months) to reduce adverse effects.
• Facial vitiligo responds best: up to 80% of patients achieve >90% repigmentation. Trunk responds in ~40%.
• For children, a class II steroid such as mometasone furoate is preferred; lower-potency steroids lack strong evidence.
• Side effects: skin atrophy, telangiectasia, hypertrichosis, acneiform eruptions, striae, and elevated intraocular pressure if used periocularly.

• Fitzpatrick's Dermatology, p. 1369; Andrews' Diseases of the Skin, p. 1002

2. Topical Calcineurin Inhibitors (TCIs) - First-Line for Face/Intertriginous Areas

• Particularly effective for facial vitiligo - in some series, as effective as superpotent corticosteroids, without steroid-induced atrophy or acne.
• Ideal for sites where steroids are problematic: face, neck, eyelids, intertriginous folds, and in children.
• Mechanism: inhibit calcineurin/T-cell activation, reducing autoimmune melanocyte destruction via the IFN-γ/JAK-STAT pathway.
• Tacrolimus 0.1% twice weekly has been shown in an RCT to maintain repigmentation as maintenance therapy (>90% maintained vs. 60% placebo).
• Patients who start treatment in summer (concurrent sun exposure) have a higher response rate.
• Combination with nbUVB significantly increases efficacy over either alone.
• Warning: the FDA black-box warning about lymphoma risk (based on oral dosing data) has not been observed with topical use; meta-analyses in atopic dermatitis confirm no increased lymphoma risk.

• Fitzpatrick's Dermatology, pp. 1369-1370; Andrews' Diseases of the Skin, p. 1002

3. Topical JAK Inhibitor: Ruxolitinib Cream (Opzelura) - Newest FDA-Approved Agent

• First and only FDA-approved topical specifically for vitiligo (approved June 2022 for non-segmental vitiligo in patients ≥12 years).
• Mechanism: inhibits JAK1/JAK2, blocking the IFN-γ/CXCL10 signaling axis responsible for melanocyte destruction and preventing melanocyte migration back into lesions.
• The pivotal TRuE-V trials demonstrated significantly greater repigmentation vs. vehicle at 24 weeks; facial BSA response was the primary endpoint.
• A 2024 meta-analysis (PMID 39134884) confirmed robust therapeutic efficacy and acceptable safety profile.
• Common side effects: application site acne, nasopharyngitis, headache.
• Systemic absorption is low but a box warning exists for serious infections and malignancy (shared class warning with oral JAK inhibitors).

4. Topical Psoralens (PUVA - Now Largely Supplanted)

• Topical psoralens (e.g., 8-methoxypsoralen cream/lotion) combined with UVA - historical first-line but now largely replaced by nbUVB.
• Higher risk of phototoxic burns and blistering than oral psoralens; restricted to small, localized lesions.
• A 2015 Cochrane review confirmed PUVA inferior to nbUVB for achieving >75% repigmentation.
• Still used when other modalities fail, particularly for limited/focal disease.

• Fitzpatrick's Dermatology, p. 1370

5. Vitamin D Analogs (Adjunctive)

• Calcipotriene and other vitamin D analogs have shown variable results as monotherapy - generally lack efficacy alone.
• Some studies show additive benefit in combination with other treatments (particularly nbUVB or steroids); others show no benefit.
• Used as adjunctive agents, not monotherapy.

• Andrews' Diseases of the Skin, p. 1002

6. Depigmentation Therapy (Monobenzene - Specialized Use)

• Monobenzone 20% cream (historically the only FDA-approved topical for vitiligo before ruxolitinib).
• Used for widespread disease (>80% BSA) - permanently depigments residual normal skin to achieve even skin tone.
• Applied 1-2x daily; takes 1-2 years for complete depigmentation. Affects areas remote from application - cannot be used for local depigmentation only.
• Permanent and irreversible. Patients require lifelong sun protection.
• Contact dermatitis in up to 20% of patients; co-prescribing topical steroids may limit the reaction.

• Fitzpatrick's Dermatology, p. 1372

7. Topical Pseudocatalase / Phenylalanine / Other Agents

• Topical pseudocatalase cream (PC-KUS) has been used based on the oxidative stress hypothesis (H₂O₂ accumulation in vitiligo skin).
• Topical phenylalanine applied before UV exposure has some limited evidence.
• Current evidence for these and other non-traditional agents (khellin, ginkgo biloba, Polypodium leukotomos topical) is weak; not recommended as primary therapy.

• Fitzpatrick's Dermatology, p. 1372

Treatment Selection Summary

Platelet Comments on Peripheral Smear in Thrombocytopenia

1. Confirm the Count (Rule Out Artifact First)

• Platelet clumping - Look at the feathered edge and body of the smear. Clumps of platelets indicate EDTA-dependent pseudothrombocytopenia (~0.1% of the general population has EDTA-dependent anti-GPIIb/IIIa IgM antibodies that agglutinate platelets in vitro). Action: repeat count in a citrate or heparin tube.
• Platelet satellitism - Platelets rosetting/adhering around neutrophils (also EDTA-dependent artifact). This also causes falsely low automated counts.
• Always state: "Platelets are confirmed decreased / cannot be confirmed due to clumping - suggest repeat in citrate tube."

• Goldman-Cecil Medicine, screening tests of hemostasis; Tietz Textbook of Laboratory Medicine, p. EDTA pseudothrombocytopenia

2. Platelet Size - The Single Most Diagnostically Useful Feature

• Harriet Lane Handbook, Evaluation of Thrombocytopenia; Quick Compendium of Clinical Pathology, §14.22

3. Platelet Morphology - Specific Findings

a. Giant / Megathrombocytes

• Size equal to or exceeding an RBC (diameter >4 µm)
• Seen in: ITP, Bernard-Soulier syndrome, MYH9-related disorders (May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, Epstein syndrome), Gray platelet syndrome, DiGeorge syndrome, Mediterranean macrothrombocytopenia
• In MYH9 disorders, also look for Döhle-like inclusion bodies in neutrophils (on the same smear) - a pathognomonic combination

b. Small Platelets

• Congenital: Wiskott-Aldrich syndrome, congenital amegakaryocytic thrombocytopenia, thrombocytopenia with absent radii (TAR syndrome)
• Glanzmann thrombasthenia (platelets are morphologically normal in size but functionally defective - here the count is normal; note this for completeness)

c. Hypogranular / Agranular Platelets ("Gray Platelets")

• Pale, grayish platelets lacking normal alpha-granules
• Seen in Gray platelet syndrome (rare autosomal recessive); alpha-granule contents (fibrinogen, vWF, factor V) are absent
• Also seen in myelodysplastic syndromes and myeloproliferative neoplasms - dysgranulation

d. Abnormally granular / Hypergranular platelets

• Dense, darkly granular platelets may be seen in reactive thrombocytosis and some MPN states (note this is not a thrombocytopenic finding, but relevant if seen alongside)

4. Associated Red Cell Changes (Co-report with platelet comment)

Schistocytes (Fragmented Red Cells)

• Helmet cells, triangular forms, microspherocytes from mechanical fragmentation
• When schistocytes + thrombocytopenia are present together = Thrombotic Microangiopathy (TMA)
  • TTP: typically >2-3 schistocytes per high-power field; severe thrombocytopenia (usually <30K/µL), with relatively normal clotting times
  • HUS: schistocytes + thrombocytopenia + renal failure; often post-diarrheal (Shiga toxin)
  • DIC: schistocytes + thrombocytopenia + prolonged PT/aPTT + low fibrinogen
  • HELLP: in pregnant patients; same MAHA picture
• Comment template: "Schistocytes noted - findings consistent with microangiopathic hemolytic anemia; TTP/HUS/DIC should be excluded."

Blast Cells / Immature White Cell Precursors

• Blasts on smear with thrombocytopenia = suspect leukemia (AML, ALL) or bone marrow infiltration
• Leukoerythroblastic picture (blasts + nucleated RBCs + teardrop cells) = bone marrow infiltration / myelofibrosis

5. The Platelet:RBC Ratio (Estimation Method)

• Each platelet seen per oil-immersion field corresponds roughly to ~10,000-15,000 platelets/µL
• If clumping is present, report: "True platelet count likely underestimated due to clumping."

6. Summary - What to Include in Every Platelet Comment

1. Quantity - Confirmed decreased / clumping present / cannot confirm
2. Size - Large / normal / small (with MPV correlation if available)
3. Morphology - Granularity, shape, any giant forms
4. Distribution - Clumping present/absent; satellitism around neutrophils present/absent
5. Associated RBC findings - Schistocytes present/absent (and approximate count per HPF)
6. Associated WBC findings - Blasts, Döhle bodies in neutrophils (MYH9 disorders), hypersegmentation
7. Diagnostic interpretation - e.g., "Large platelets with no schistocytes - consistent with peripheral destruction (ITP-like picture)" OR "Thrombocytopenia with schistocytes - microangiopathic process cannot be excluded"

Quick Reference: Smear Pattern - Likely Diagnosis

Sources: Quick Compendium of Clinical Pathology, §14.7, §14.22; Harriet Lane Handbook, Table 14.9; Goldman-Cecil Medicine; Frameworks for Internal Medicine