Understanding "Hierarchy" in Dermatology Treatment
In dermatology, "hierarchy" refers to a structured, stage-based treatment algorithm that progresses from least aggressive to most aggressive therapies, prioritizing skin-directed treatments before advancing to systemic interventions, with the goal of maximizing disease control while minimizing long-term toxicity and preserving quality of life.
Definition and Concept
Hierarchy represents a stepwise treatment approach where therapeutic interventions are organized by increasing intensity, invasiveness, and potential toxicity 1.
The hierarchical model in dermatology follows the principle of starting with conservative, localized therapies and escalating only when disease is refractory or advances 1, 2.
This framework is particularly critical in chronic conditions where long-term treatment safety must be balanced against disease control, as patients may require therapy for years or decades 1.
Hierarchy Applied to Mycosis Fungoides (MF)
The treatment hierarchy for MF exemplifies this concept clearly, with distinct treatment lines based on disease stage:
First-Line (Early Stage IA-IIA)
Skin-directed therapies (SDT) form the foundation of early-stage treatment 1, 2.
Options include:
- Topical corticosteroids (class 1/very potent compounds) 1
- Topical mechlorethamine (nitrogen mustard 0.02%) - FDA-approved for Stage IA/IB MF 3
- PUVA (psoralen plus UVA) with response rates of 79-88% in stage IA 2
- Narrow-band UVB for patches or very thin plaques 2
- Localized radiotherapy (8 Gy in two fractions for plaques/tumors) 1
The British Association of Dermatologists emphasizes that SDT should be exhausted before advancing to systemic therapy 1.
Second-Line (Refractory Early Stage or Stage IIB)
Combination therapies or systemic biologics are introduced when SDT fails 1, 2.
Options include:
Patients with stage IB disease refractory to SDT should be referred to supranetwork multidisciplinary teams for access to clinical trials and specialized treatments 1.
Third-Line (Advanced Stage III-IV)
Systemic immunotherapies and targeted agents are reserved for advanced or refractory disease 1, 2.
Options include:
Chemotherapy is reserved only for patients with effaced lymph nodes, visceral involvement (stage IV), or widespread tumor-stage MF uncontrolled by other therapies 1, 2.
Single-agent options (gemcitabine, liposomal doxorubicin) are preferred over multi-agent regimens due to better tolerability 2.
Fourth-Line (Refractory Advanced Disease)
Allogeneic stem cell transplantation may be considered in young patients with refractory, progressive disease 1, 2.
Reduced-intensity allogeneic stem cell transplantation (RIC-allo-SCT) is recommended only after exhausting first-, second-, and third-line options 1.
Key Principles of Hierarchical Treatment
Stage-Based Escalation
Treatment intensity must match disease stage - early-stage disease (IA-IIA) receives SDT, while stage IIB or higher requires systemic therapy 1, 2.
The British Association of Dermatologists mandates that all patients with stage IIB or higher MF should be reviewed by supranetwork MDTs 1.
Avoiding Premature Aggressive Therapy
Early aggressive chemotherapy is associated with considerable side effects but does not improve survival 1, 2.
Cumulative toxicity from treatments like PUVA should be limited (maximum 1200 J/cm² and/or 250 sessions) to prevent secondary skin cancers 1.
Maintenance PUVA therapy should generally be avoided as risks may outweigh benefits, though exceptions exist for refractory patients requiring symptomatic relief 1.
Multidisciplinary Review Points
Patients requiring specialist treatments (TSEB, ECP) must be reviewed by supranetwork MDTs 1.
All patients being considered for stem cell transplantation require supranetwork MDT review 1.
Common Pitfalls and Caveats
Diagnostic Delays
MF often mimics common inflammatory dermatoses (eczema, psoriasis), leading to delayed diagnosis 5.
Multiple skin biopsies may be required, especially in patch stage, to identify characteristic epidermotropic infiltrates 5.
Treatment-Related Complications
Topical mechlorethamine can cause severe mucosal or eye injury leading to blindness - immediate 15-minute irrigation is required if exposure occurs 3.
Secondary exposure risk exists - individuals other than the patient must avoid skin contact with mechlorethamine 3.
Phototherapy may contribute to mutations that increase tumor cell proliferation and invasiveness 1.
Non-melanoma skin cancer risk increases with cumulative PUVA exposure - monitoring during and after treatment is essential 3.
Realistic Treatment Goals
Long-term cure may be achieved only in localized disease (pagetoid reticulosis), while multifocal early-stage disease typically achieves only short-term clinical response with recurrent disease over many years 2.
The realistic goal for advanced MF is achieving long-lasting remissions without long-term toxicity, not cure 1.
In treatment-resistant late-stage disease, palliative radiotherapy and/or chemotherapy may produce significant short-term benefit, but quality of life should always be given priority 2.
Hierarchy in Other Dermatologic Conditions
While MF provides a clear example, the hierarchical approach applies broadly across dermatology:
Inflammatory conditions typically start with topical corticosteroids before advancing to systemic immunosuppressants 6.
Neoplastic conditions follow similar principles of local treatment before systemic intervention when appropriate 6.
The accessibility of skin as an organ facilitates both diagnosis and treatment, allowing effective management of many conditions through externally applied physical or pharmacological modalities before resorting to systemic administration 6.