Mechanism: Binds to glucocorticoid receptors directly in cell, inhibiting nuclear factor-κB, decreasing inflammation. Also inhibits TNF-α, GM-CSF, and several interleukins

Immediate side effects: Accelerated release of neutrophils from bone marrow (neutrophilia) and demargination, transient lymphopenia, hyperglycemia, hypertension, mood changes/psychosis/insomnia, acneiform eruptions, weight gain/increased appetite, GI effects/peptic ulcers

Later side effects: osteoporosis (most significant demineralization in first 6–12 months of therapy), adrenal suppression, avascular necrosis of femoral head/osteonecrosis, cataracts (posterior subcapsular – opposed to anterior cataracts from atopic dermatitis), Cushing syndrome, poor wound healing/striae, risk of infection

Note: alternate-morning regimens may decrease some effects (hyperglycemia, risk of adrenal suppression), but not cataracts or osteoporosis (effect is from total dose and duration)

Interactions: Active TB, systemic fungal infection, depression/psychosis, HTN, DM

Mechanism: Inhibits inosine monophosphate (IMP) dehydrogenase, blocking guanine (purine) synthesis. Considered more specific inhibition than azathioprine since only affects B and T lymphocyte cell lines (salvage pathway still intact)

Side effects: GI effects, heme/hepatic toxicity rare

Interactions: With iron, forms complex that decreases absorption

Pregnancy category D

Mechanism: 6-mercaptopurine pro-drug. Inhibits purine synthesis enzymes. Metabolism: metabolized by both thiopurine methyltransferase (TPMT) and xanthine oxidase into non-toxic metabolites, HGPRT into active metabolite, 6-thioguanine (resembles adenosine and guanine). If TPMT deficient or xanthine oxidase blocked (allopurinol), immunosuppression greatly increased.

Side effects: Pancytopenia, increased lympoproliferative malignancies, SCCs, pancreatitis. Can have hypersensitivity reaction (morbilliform eruption) in 1st month, especially when given with MTX or cyclosporine

Interactions: Check TPMT, allopurinol (xanthine oxidase inhibitor), captopril (increase risk leukopenia), or warfarin (decreased effectiveness)

Pregnancy category D

→ (xanthine oxidase) [inhibited by allopurinol]

→ (HGPRT) [mutations cause Lesch-Nyhan syndrome]

→ (thiopurine methyltransferase = TPMT) [this can have variable activity from genetic polymorphism]

Hydroxychloroquine (Plaquenil), chloroquine (Aralen), quinacrine

Note: G6PD, regular eye exam indicated

Uses: lupus, photodermatoses, porphyria cutanea tarda (PCT)

Mechanism: Not well known (intercalates DNA?); can inhibit IL-2 release

Side effects: blue-gray to black discoloration (pretibial > nail > other; yellow with quinacrine), rarely retinopathy, pancytopenia, hemolysis (in G6PD deficiency). Only quinacrine has no ocular toxicity.

Interactions: Increased retinal toxicity when hydroxychloroquine and chloroquine together (so these two never combined, only either with quinacrine); smoking may decrease effectiveness of antimalarials in lupus

Uses: psoriasis, atopic dermatitis, TEN

Mechanism: Downregulates IL-2 (and thus Th1 T cells)

Side effects: Hypertension (check BP), renal failure (check urine), hypertrichosis, gingival hyperplasia, SCCs; hypomagnesemia, hyperkalemia (avoid potassium sparing diuretics)

Interactions: narrow therapeutic window and mostly metabolized by CYP450 3A4

Pregnancy category C

Mechanism: binds to FK506-binding protein forming inhibitors of phosphatase calcineurin, preventing dephosphorylation of NFAT

Uses: neutrophilic dermatoses (Sweet’s, PG, LCV, EED, linear IgA, DH, bullous LE), leprosy, bullous pemphigoid

Mechanism: Inhibits neutrophil myeloperoxidase, which is required for respiratory burst (a sulfone)

Side effects: hemolysis (in everybody), methemoglobinemia (can be prevented with cimetidine or Vitamin E, tx with methylene blue); long term (rare) = agranulocytosis (occurs in first week to first 3 months presenting with fever, pharyngitis, signs of sepsis), peripheral neuropathy (motor > sensory, e.g. wasting of hands, foot drop), dapsone hypersensitivity syndrome (like DRESS with fever, rash, hepatitis, eosinophilia)

Interactions: G6PD deficiency

Pregnancy category C

Topical form (Aczone) for acne; methemoglobinemia reported

Uses: neutrophilic dermatoses, LCV

Mechanism: Binds to tubulin and prevents microtubule assembly, blocks neutrophil chemotaxis/adhesion/degranulation (similar to podophyllin, griseofulvin)

Side effects: GI side effects common

Pregnancy category C

Uses: erythema nodosum leprosum (drug of choice), pruritus, sarcoidosis, lupus

Mechanism: inhibits TNF-α

Side effects: symmetric painful parasthesias, teratogenic (phocomelia)

Uses: immunosuppression in kidney transplant; now has potential for treating neoplasms given tumor suppressor activity (tuberous sclerosis)

Note: may decrease risk of SCCs in transplant patients compared to other transplant regimens

Mechanism: inhibits mTOR (mammalian target of rapamycin) which is a proto-oncogene in the RAS-PI3K pathway usually inhibited by a tumor suppressor made by hamartin and tuberin (either may be mutated in tuberous sclerosis); despite similar name (sirolimus) to tacrolimus and pimecrolimus, sirolimus/rapamycin is not a calcineurin inhibitor, but it does similarly suppress IL-2; all three are non-antibiotic macrolides (unlike erythromycin, azithromycin).

Uses: only FDA approved for GVHD, but also used for blistering diseases, SJS/TEN, Kawasaki disease

Mechanism: provides passive immunity; in TEN, may block Fas-Fas ligand interaction

Notes: Check IgA level (small risk of anaphylaxis if IgA deficient); relative contraindications include CHF and renal failure (risk of fluid overload).

Sucrose preparations can induce an osmotic nephrosis → acute renal failure.

Pregnancy category C

Uses: erythema nodosum, sporotrichosis, Sweet’s syndrome (and other neutrophilic dermatoses)

Mechanism: thought to inhibit neutrophil chemotaxis, and by mast cell heparin degranulation

Side effects: Wolff-Chaikoff effect (affects thyroid metabolism, can cause fetal goiter), iododerma, can flare dermatitis herpetiformis (and some neutrophilic dermatoses)

Uses: derm/rheum diseases, medical abortion, chemotherapy

Mechanism: folic acid analog, irreversible inhibitor of dihydrofolate reductase (DHFR) and required for de novo synthesis of purine nucleotides

Side effects: nausea (relieved by folic or folinic acid), pancytopenia, hepatoxicity (after years), radiation recall, pulmonary fibrosis, pneumonitis, teratogenicity, accelerated rheumatoid nodulosis

Interactions: With sulfa drugs (e.g. TMP/SMX), dapsone, markedly increased pancytopenia (synergistic DHFR inhibition, plus decreased plasma protein binding/renal excretion). NSAIDs/salicylates displace MTX from plasma proteins, lower renal excretion, increasing toxicity. Retinoids, alcohol synergistic for liver disease.

Contraindications: liver disease, alcohol

Note: recent studies suggest that adenosine may play a role in MTX resistance

Pregnancy category X – wait at least 3 months after medication stopped to conceive

Uses: rheumatologic diseases

Mechanism: pyrimidine synthesis inhibitor

Uses: psoriasis in HIV patients

Mechanism: inhibits M2 subunit of ribonucleotide reductase

Side effects: Can cause leg ulcers, dermatomyositis (poikiloderma of dorsal hands), megaloblastosis (in 100 %), anemia (~25 %), radiation recall, hyperpigmentation

Pregnancy category D

Uses: granulomatosis with polyangiitis (GPA), MPA, PAN, ocular cicatricial pemphigoid (first line), CTCL, hematologic malignancies

Mechanism: cross-links DNA, derived from nitrogen mustard, alkylating agent

Side effects: hemorrhagic cystitis (can lead to transitional cell carcinoma, prevent with mesna)

Pregnancy category D

Uses: AKs, SCCIS

Mechanism: pyrimidine analog, inhibits thymidylate synthetase

Side effects (IV): serpentine supravenous hyperpigmentation

Pregnancy category D

Uses: periungual/palmoplantar/treatment-resistant warts (intralesional)

Mechanism: inhibits DNA synthesis

Side effects: flagellate hyperpigmentation, NEH, radiation recall, Raynaud’s

Pregnancy category D

Cyclophosphamide

Hydroxydaunorubicin (aka doxorubicin or Adriamycin)

Oncovin (vincristine)

Prednisone

(Optional: rituximab can be added for R-CHOP)

Uses = acute promyelocytic leukemia

Side effects: can cause Sweet’s syndrome

Pregnancy category D