Psoriasis treatment: Unconventional and non-standard modalities in the era of biologics

Table 1 Therapeutic options for psoriasis

Topical agents	Systemic agents	Phototherapy
Emollients Tar and anthralin Dithranol Corticosteroids Vitamin D analogs Tazarotene Salicylic acid Tacrolimus/ pimecrolimus 5-fluorouracil Ascomycin derivatives	Methorexate Retinoids Cyclosporine A Hydroxyurea Tacrolimus Mycophenolate mofetil Sulfasalazine 6-thioguanine Calcitriol Colchicine Dapsone Azathioprine Fumaric acid esters Biologics: Etanercept, Alefacept, Infliximab, Efalizumab, Adalimumab	Natural Dead Sea Therapy and PUVA-Sol Artificial PUVA, Bath PUVA, UVB and NB-UVB Newer Excimer laser, NB-UVB light enhanced Photodynamic therapy

UV: Ultraviolet light; PUVA: Psoaralene ultraviolet A; Sol: Solar; NB-UVB: Narrow band UV.

Table 2 Adverse effects of methotrexate therapy

System involved	Adverse effects
General	Fatigue, headaches, chills and fever, dizziness
Skin	Pruritus, pain and burning, urticaria, mild reversible alopecia, ecchymosis, acute ulcerations of psoriatic lesions, reactivation of phototoxic responses
Blood	Bone marrow depression, leukopenia leading to decreased resistance to infection, anemia, thrombocytopenia, bleeding, and megaloblastic anemia, Pancytopenia
Gastrointestinal system	Nausea and anorexia, diarrhea, vomiting, ulcerative stomatitis, pharyngitis, enteritis
Urinary system	Azotemia, microscopic hematuria, cystitis, nephropathy
Respiratory system	Acute pneumonitis, pulmonary fibrosis
Nervous system	Headaches, dizziness, drowsiness, blurred vision, acute depression
Reproductive system	Teratogenesis, defective oogenesis, menstrual dysfunction, reversible oligospermia, defective spermatogenesis
Uncommon side effects	Anaphylaxis, acral erythema, epidermal necrosis, vasculitis, osteopathy, lymphoma

Table 3 Methotrexate drug interactions of significance

Interacting drug	Mechanism/comments
Drugs that increase methotrexate drug levels and toxicity
Salicylates	Decrease renal excretion, displacement from plasma proteins
NSAIDs	Decrease renal excretion, displacement from plasma proteins
Sulfonamides	Decrease renal excretion, displacement from plasma proteins
Dipyridamole	Increased intracellular accumulation of methotrexate
Probenecid	Increased intracellular accumulation of methotrexate, decreased renal tubular function
Chloramphenicol	Displacement from plasma proteins
Phenothiazines	Displacement from plasma proteins
Phenytoin	Displacement from plasma proteins
Tetracyclines	Displacement from plasma proteins
Drugs that simultaneously inhibit folate metabolic pathway-increase hematologic toxicity
Trimethoprim	Inhibition of dihyrofolate reductase
Sulfonamides	Inhibition of dihydropteroate synthetase
Dapsone	Inhibition of dihydropteroate synthetase
Drugs that may synergistically increase hepatotoxicity-common target organ
Systemic retinoids	Common target organ for toxicity-liver
Alcohol	Common target organ for toxicity-liver

NSAID: Nonsteroidal anti-inflammatory drug.

Table 4 Guidelines for monitoring psoriasis patients receiving methotrexate by utilizing PIIINP levels

Indications for considering withdrawal of methotrexate	Elevation of PIIINP above 10.0 μg/L in at least 3 samples in one 12-mo period
Indications for considering liver biopsy	Elevation of pretreatment PIIINP above 8.0 μg/L
	Elevation of PIIINP above 8.0 μg/L in 2 consecutive samples
	Elevation of PIIINP above the normal range (1.7-4.2 μg/L) in at least 3 samples over a 12 mo period
Remarks: Serum for PIIINP measurement should be collected prior to starting methotrexate and should subsequently be measured every 2-3 mo during continued treatment

Table 5 Grading of Liver biopsy as per Roenigk scale and recommendations for further methotrexate therapy

Biopsy grade	Liver histopathologic findings	Recommendation
I	Normal; fatty infiltration, nuclear	May continue methotrexate
	Variability and portal inflammation- mild
II	Fatty infiltration, nuclear variability, portal tract expansion, inflammation and necrosis- moderate to severe
IIIA	Fibrosis-mild	May use methotrexate with caution and repeat biopsy at 6 mo
IIIB	Fibrosis-moderate to severe	Should not be given except in exceptional circumstances
IV	Cirrhosis

Table 6 Drugs interacting with retinoids

Interacting drug	Mechanism/comments
Drugs that may increase retinoids levels and/or toxicity
Vitamin A	Induces hypervitaminosis A like toxicities
Tetracycline, doxycycline and minocycline	Increase pseudotumour cerebri risk
Macrolides, Azoles, etc.	Other CYP 3A4 inhibitors increase its level
Drugs that may reduce retinoids level
Rifampicin, rifabutin	Induction of CYP 3A4
Anticonvulsants-phenytoin, Phenobarbital, carbamazepine	Induction of CYP 3A4
Drugs that may synergistically increase hepatotoxicity
Methotrexate	Common target organ for toxicity-liver
Alcohol	Common target organ for toxicity-liver
Drugs whose levels are changed by retinoids
Cyclosporine A	Cyclosporine A levels are increased via competition for CYP 3A4