eMedicine Specialties > Ophthalmology > Conjunctiva
Cicatricial Pemphigoid: Treatment & Medication
Updated: Dec 12, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
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Treatment
Medical Care
No topical agent is effective in stopping OCP activity. In selected patients, subconjunctival steroid injections or subconjunctival injections of mitomycin C may be used temporarily for slowing disease progression, while systemic therapy takes effect.
Adjuvant treatment with topical lubricants should be used in patients with dry eye symptoms. The use of topical cyclosporine and tacrolimus ointment has also been described in anecdotal reports to aid in the control of surface inflammation.
- Systemic corticosteroids can control the activity of the disease; however, they are not as effective as other immunosuppressive drugs, and the doses required have been shown to be very toxic. Additionally, tapering of systemic steroids has always been associated with recurrence of disease activity, suggesting the need of high doses for extended periods of time. Because of the toxicity of long-term corticosteroid use (eg, aseptic hip necrosis, pathological fractures, uncontrolled diabetes mellitus, hypertension), it is an unacceptable treatment. Corticosteroids should never be used as a sole agent. Their use should be reserved only for severely inflamed eyes that do not readily respond to immunosuppression alone. When administered, corticosteroids should be used for a limited period of time, preferably not longer than 3 months.
- Long-term use (>1 y) of systemic immunomodulators is the major therapeutic strategy in treating OCP. The current guidelines for using chemotherapy in treating OCP are as follows:
- For mild-to-moderate inflammation, diaminodiphenylsulfone (Dapsone) is a first-line agent, provided the patient is not glucose-6-phosphate dehydrogenase deficient. Methotrexate may also be considered first-line therapy. If therapeutic response is not satisfactory, or if the use of Dapsone is contraindicated, or if the patient cannot tolerate the drug, mycophenolate mofetil or azathioprine can be substituted. If inflammation persists, cyclophosphamide can be used sequentially.
- For severe inflammation, cyclophosphamide should be used initially, and systemic prednisone could be added with rapid taper for a limited period of time (3 mo).
- Patients with active conjunctival inflammation refractory to chemotherapy or patients who do not tolerate the spectrum of immunosuppressive drugs can be treated with intravenous immunoglobulin (IVIg) or a combination of IVIg and rituximab infusions.
Surgical Care
Ocular surgical procedures should only be performed when the inflammation is completely under control, and systemic corticosteroids should be used perioperatively, when the procedure involves the conjunctiva or the cornea. Once the inflammation is suppressed, such procedures as marginal rotation of the eyelid, mucous membrane grafting, retractor plication, fornix reconstruction, or cataract extraction can be performed without significant danger of excessive postoperative inflammation and cicatrization.
- Epilation
- Aberrant lash growth that produces damage to the ocular surface is common in OCP. Extraction of these lashes and destruction of the follicles is important not only to prevent further irritation of the ocular surface but also to remove a factor that can mimic immunologically driven conjunctival inflammation, thereby hindering judgment regarding clinical response to chemotherapy and disease activity.
- Mechanical epilation has only a temporary effect, and the lashes that regrow may be more deleterious than the original lashes. Gas permeable scleral contact lenses can be used to provide protection to the ocular surface from injury by aberrant lashes.
- In case of trichiasis or distichiasis, permanent destruction of the lash follicles is ideal, although not easy to provide. Cryodestruction of lash follicles requires subsequent epilation in 10% of patients. The recurrences can be retreated.
- Punctual occlusion
- Treat dry eye syndrome with punctal occlusion and ocular lubricants without preservatives. Ocular hydration also can be increased with the use of twice daily mild steroid and topical cyclosporine.
- Treat meibomian gland dysfunction with warm compresses and lid massages with eyelid hygiene, with or without systemic tetracycline therapy.
- Lid surgery
- Entropion surgery usually is avoided in patients with OCP because of the interference with the conjunctiva. Recently, several cases of lower lid entropion have been treated successfully with a retractor plication technique. The procedure is repeatable in case of undercorrection. Moreover, the conjunctiva remains intact during the surgery, which can avoid the exacerbation of conjunctival inflammation.
- Tarsorrhaphy can be used in case of lagophthalmos, corneal hypoesthesia, or corneal epithelial defects.
- Fornix reconstruction
- Amniotic membrane transplantation or autologous oral mucosa can be used to reconstruct the conjunctival fornices in patients with OCP.
- Mucous membrane grafting should not be performed when patients have severe keratoconjunctivitis sicca, advanced OCP, or active conjunctival inflammation. The procedure not only reconstructs the anatomy of fornices but also provides nonkeratinizing epithelium with goblet cells supplying mucous production to the ocular surface.
- The beneficial long-term effect of this procedure is provided in approximately one third of the patients.
- Corneal surgery
- The visual acuity in patients with OCP is impaired mostly by corneal pathology. Unfortunately, the spectrum of procedures on the cornea providing a satisfactory long-term visual outcome is very limited. Corneal transplantation on a dry eye with impaired lid function and limbal stem cell deficiency has a very poor prognosis; therefore, corneal grafting in patients with advanced OCP should be avoided. This procedure should only be performed in case of corneal perforation.
- In patients with advanced corneal damage from OCP, keratoprosthesis may be the only feasible alternative for visual rehabilitation. Necrosis of the tissue surrounding the prosthesis is the major problem limiting the long-term outcomes. This process can lead to aqueous leak, retinal detachment, infection, and extrusion of the prosthesis. Recent advances in keratoprosthesis along with lifelong use of topical antibiotics have improved the outcome. At one facility, 5-8 patients had considerable improvement of visual acuity over a 5-year period.
- Cataract surgery
- The need for cataract surgery is common in patients with OCP. Cataract surgery performed on patients with OCP is followed by increased conjunctival inflammation, rapid progression of keratopathy, and conjunctival scarring, if the disease is not medically controlled.
- The results of one study showed that a worse outcome of cataract surgery was associated with chemotherapy intolerance or the presence of any preoperative conjunctival inflammation. Similar to other surgical procedures for OCP, the use of perioperative systemic steroids is necessary in patients who are on systemic immunosuppressive therapy and in those patients whose inflammation is currently in remission without taking any immunosuppressive agents.
Consultations
- Consult an appropriate specialist in case of skin involvement or involvement of other mucous membranes. Patients who have difficulty swallowing or breathing require an immediate endoscopic examination looking for esophageal webs, as these patients are at risk of asphyxiation.
- Patients receiving chemotherapy may require regular consultations with a chemotherapeutist.
- Patients should be referred to an ear, nose, and throat specialist for laryngoscopy in case of recent onset of hoarseness, which may be caused by laryngeal stenosis and tracheal scarring. These patients are in a medical emergency because of the risk of mucous accumulation and subsequent fatal asphyxiation. A statim laryngoscopy is essential, and it may be a life-saving procedure.
Activity
Patients may be limited by visual acuity.
Medication
The goal of pharmacotherapy is to reduce morbidity and to prevent complications. Combination therapy in a stepladder regimen is needed in many cases to improve disease control.
Antibiotics
Therapy must be comprehensive and cover all likely pathogens in the context of the clinical setting.
Dapsone (Avlosulfon)
Recommended as first-line agent for treatment of OCP if inflammatory activity is not severe, disease is not rapidly progressive, and patient is not glucose-6-phosphate dehydrogenase deficient. A response usually is observed within 4 weeks of initiation of therapy. Has both antimicrobial and anti-inflammatory activity. Mechanisms by which it influences inflammatory and immune systems are not clear. Able to penetrate bacterial cells and have both bactericidal and bacteriostatic activity against Mycobacterium leprae. Believed to mediate anti-inflammatory effects in cicatricial pemphigoid by a variety of mechanisms. Evidence suggests that dapsone stabilizes lysosomal membranes, decreasing release of contents, and interferes with myeloperoxidase halide-mediated cytotoxic system of neutrophils. May inhibit Arthus reaction and adjuvant-induced arthritis in a manner similar to that of corticosteroids and indomethacin.
Adult
25 mg PO bid for 1 wk initially; increase to 50 mg bid and adjust dose based on clinical response and drug tolerance, not to exceed 150 mg/d; taper slowly to maintenance level once inflammatory process is under control
Pediatric
1 mg/kg PO divided bid; not to exceed 100 mg/d
May inhibit anti-inflammatory effects of clofazimine; hematologic reactions may increase with folic acid antagonists, eg, pyrimethamine (monitor for agranulocytosis during the second and third months of therapy); probenecid increases dapsone toxicity; trimethoprim with dapsone may increase toxicity of both drugs; because of increase in renal clearance, dapsone levels may significantly decrease when administered concurrently with rifampin
Documented hypersensitivity; known G-6-PD deficiency
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Perform weekly blood counts (first month); then perform WBC counts monthly (6 mo); then semi-annually; discontinue if significant reduction in platelets, leukocytes, or hematopoiesis is seen
Caution in methemoglobin reductase deficiency, G-6-PD deficiency (patients receiving >200 mg/d), or hemoglobin M because of high risk for hemolysis and Heinz body formation; caution in patients exposed to other agents or conditions (eg, infection, diabetic ketosis) capable of producing hemolysis; death resulting from agranulocytosis, aplastic anemia, and other blood dyscrasias has been reported in association with dapsone treatment; phototoxicity may occur when exposed to UV light
Additional adverse effects include reversible peripheral neuropathy, toxic hepatitis, cholestatic jaundice, GI intolerance, cutaneous hypersensitivity reactions, and potentially fatal mononucleosislike syndrome (rare), possibly from a hypersensitivity reaction characterized by fever, malaise, exfoliative dermatitis, methemoglobinemia, anemia, lymphadenopathy, and hepatomegaly with jaundice; eosinophilia and an increased number of atypical lymphocytes are generally present; condition improves with dapsone discontinuation and institution of corticosteroid therapy
Immunosuppressive agents
Inhibit cell growth and proliferation.
Methotrexate (Folex, Rheumatrex)
Chemical structure analogous to that of folic acid. Prevents conversion of dihydrofolate to tetrahydrofolate by competitively and irreversibly binding to enzyme dihydrofolate reductase. Tetrahydrofolate is an essential cofactor in production of 1-carbon units critical to synthesis of purine nucleotides and thymidylate. Less rapid, partially reversible competitive inhibition of thymidylate synthetase occurs within 24 h after methotrexate administration. Net effect is inhibition of DNA synthesis, DNA repair, RNA synthesis, and cell division at specific stages of the cell cycle.
Has little effect on resting cells. Exerts cytotoxic actions in actively proliferating tissues such as malignant cells, fetal cells, cells of GI tract, urinary bladder, buccal mucosa, and bone marrow. By inhibiting DNA synthesis in immunologically competent cells, methotrexate has some activity as immunosuppressive agent. Both B and T cells are affected, and primary and secondary antibody responses can be suppressed when administered during antigen encounter. To date, no controlled data in humans or animals indicate that methotrexate is carcinogenic.
Adult
2.5-7.5 mg/wk PO/IV/IM single dose or divided q36-48h; increase dose gradually as dictated by clinical response, not to exceed 25 mg/wk
Pediatric
5-15 mg/m2/wk PO/IM single dose or 3 divided doses 12 h apart
Oral aminoglycosides may decrease absorption and blood levels of concurrent oral methotrexate (MTX); charcoal lowers MTX levels; coadministration with etretinate may increase hepatotoxicity of MTX; folic acid or its derivatives contained in some vitamins may decrease response to MTX; coadministration with NSAIDs may be fatal; indomethacin and phenylbutazone can increase MTX plasma levels; may decrease phenytoin serum levels; probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase effects and toxicity of MTX; may increase plasma levels of thiopurines
Documented hypersensitivity; breastfeeding women; alcoholism, alcoholic liver disease, or chronic liver disease of any etiology; immunodeficiency states (irrespective of cause); preexisting blood dyscrasias or bone marrow suppression
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Myelosuppression is major dose-limiting toxicity; leucovorin is given to rescue bone marrow, optimally in 6-8 h after methotrexate administration, and is continued for 72 h thereafter; hepatotoxicity may develop after short- and long-term use; acute liver toxicity, manifested by transient increase in serum transaminases may be evident within a few days of high-dose methotrexate administration; chronic, low-dose methotrexate therapy, as commonly used, may lead to hepatic fibrosis and, occasionally, to cirrhosis; liver function tests are not reliable indexes of development of hepatic fibrosis (liver biopsy is definitive); pulmonary toxicity, including acute pneumonitis and pulmonary fibrosis, has been reported with both low- and high- dose methotrexate therapy; pneumonitis presents with a dry nonproductive cough with dyspnea, high fever, and hypoxemia and probably represents either an idiosyncratic reaction or hypersensitivity (usually responds to discontinuation of MTX and brief systemic steroid therapy);GI
toxicities include nausea, ulcerative mucositis, and diarrhea, all of which may respond to dosage reduction; alopecia, dermatitis, and acute renal failure due to precipitation of drug in renal tubules may occur with high-dose regimens; ocular adverse effects are not uncommon; they include irritation, photophobia, aggravation of seborrheic blepharitis, and epiphora in 25% of patients; signs and symptoms usually abate with time and do not necessitate discontinuation of drug
Azathioprine (Imuran)
Prodrug quickly metabolized in liver to active form, 6-MP, which in turn interferes with purine metabolism and ultimately with DNA, RNA, and protein synthesis.
Shown to suppress both B and T lymphocytes. Effective in suppressing mixed lymphocyte reaction in vivo and recirculating T lymphocytes that are in the process of homing. Also can suppress development of monocyte precursors and thus participation of K cells (which themselves are derived from monocyte precursors) in antibody-dependent cytotoxicity reactions.
Reduce dose by 25% if allopurinol is administered concomitantly, since allopurinol interferes with metabolism of 6-MP8.
Adult
2-3 mg/kg PO qd or divided doses, suggested
Pediatric
Initial dose: 2-5 mg/kg/d PO
Maintenance dose: 1-2 mg/kg/d PO
Toxicity increases with allopurinol (reduce dose by 25%); concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of MTX metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine; clearance of azathioprine may be affected by drugs that inhibit (ketoconazole, erythromycin) or induce (phenytoin, rifampin, phenobarbital) hepatic microsomal enzyme system
Documented hypersensitivity; immunosuppressed patients; rheumatoid arthritis previously treated with alkylating agents (risk of neoplasia is potentially high).
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Bone marrow suppression with leukopenia and thrombocytopenia are common; typically, myelosuppression is delayed, appearing 1-2 wk after initiation of therapy, and may persist for days to weeks after drug has been discontinued; prompt dosage reduction or withdrawal of azathioprine may be necessary if myelosuppression is severe; symptomatic GI discomfort (nausea, vomiting, and diarrhea) is most common adverse effect and principal reason for discontinuation of azathioprine therapy; other adverse effects include interstitial pneumonitis, hepatocellular necrosis, pancreatitis, stomatitis, alopecia and, rarely, secondary infections
May potentiate risk of neoplasia, especially leukemia and lymphomas, in transplant patients (several studies have shown no difference in frequency of malignancy in general population from that observed in patients with rheumatoid arthritis receiving conventional doses of azathioprine)
Avoided, whenever possible, giving to pregnant women because has been shown to bemutagenic
and
teratogenic in laboratory animals and to cross placenta in humans; conception also should be avoided for a period of not less than 12 wk after discontinuation of therapy; use of azathioprine in breastfeeding mothers is not recommended because drug or metabolites are transferred at low levels in breast milk; patients with impaired renal function, especially elderly patients, or who have just undergone kidney transplantation, may have delayed clearance of azathioprine and its metabolites and, thus, requires dosage adjustments to avoid toxic sequelae
Cyclophosphamide (Cytoxan, Neosar)
Belongs to nitrogen mustard family of alkylating agents. Prodrug that must be converted in vivo by hepatic microsomal cytochrome P-450 mixed function oxidase system into its active metabolites, phosphoramide mustard and 4-hydroxy-cyclophosphamide. Products act through nucleophilic substitution reactions resulting in formation of covalent cross linkages (alkylation) with DNA, thereby mediating their major immunosuppressive activity.
At clinical doses, has profound effect on lymphoid cells. Both B- and T-cell function are depressed, although with acute administration of high doses of drug, B cells appear to be more affected.
It is preferred that patients take total daily dose in morning and maintain adequate oral fluids throughout rest of day, in an effort to induce frequent voiding. In this way, risk of hemorrhagic cystitis from prolonged contact of bladder mucosa with cyclophosphamide metabolites is minimized.
Intravenous administration of cyclophosphamide offers certain advantages overoral
administration and is useful in the following clinical situations: (1) permits rapid induction in patients with severe ocular inflammatory involvement; (2) avoids prolonged bladder exposure, allowing larger doses, yet less frequent dosing in patients with hemorrhagic cystitis induced from oral intake; and (3) induces only transient neutropenia, making intercurrent infections less likely
Adult
1-2 mg/kg/d PO/IV, suggested; these authors administer 500 mg/m2 IV in 250 cc normal saline, piggy-backed onto second half of 1 L 0.5% dextrose in water, infused over 2-h period; infusions are repeated q3-4wk, depending on clinical response and nadir of leukocyte count
Pediatric
Administer as in adults
Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects of cyclophosphamide; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life of cyclophosphamide while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity of cyclophosphamide; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Documented hypersensitivity; severely depressed bone marrow function
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
As many as 70% of patients experience anorexia, nausea, vomiting, or stomatitis, effects that apparently are dose related; for doses these authors use in care of patients with ocular inflammation, incidence of such adverse effects is much lower; 5-30% of patients receiving intensive or prolonged therapy, may experience alopecia, which is usually reversible
Most common dose-limiting toxicity of cyclophosphamide is bone marrow depression; the leukocytes being more significantly affected than platelets; nadir of leukopenia usually occurs within 1-2 wk after IV therapy is initiated; recovery is observed within 10 d of last dose; a relatively common and well-recognized dose-limiting adverse effect is sterile hemorrhagic cystitis, which results from high concentrations of active metabolites (eg, acrolein) in bladder; onset of complications is variable, occurring as early as 24 h after initiation of therapy to as late as several wk after drug discontinuation (should this complication arise, patients must undergo cystoscopy); has been associated with development of secondary malignancies, most commonly acute myelocytic leukemia and bladder carcinoma, in patients with intercurrent neoplastic, rheumatologic, or renal disease who have received cumulative doses in excess of 76 g; has been recommended that patients who have received daily doses in excess of 50 mg cyclophosphamide for more than 2 y or who have experienced multiple episodes of hemorrhagic cystitis undergo routine screening including yearly urine cytology; if suspicious or malignant cells are present, performing a biopsy of abnormal areas is mandatory
Gonadal dysfunction, including azoospermia and amenorrhea, has been observed in 60% of patients after 6 mo of treatment; sperm banking is advisable before initiation of therapy, particularly if protracted therapy is anticipated
Ocular adverse effects have been reported, including dry eyes in as many as 50% of patients treated, blurred vision, and increased intraocular
pressure (mechanism underlying those adverse effects or a causal link to cyclophosphamide therapy itself is poorly defined); other less common adverse effects include cardiac myopathy (with large doses), hepatic dysfunction, irreversible pulmonary fibrosis, impaired renal clearance of water with resultant hyponatremia, and anaphylaxis
Mycophenolate mofetil (CellCept)
Has been shown useful in moderate OCP in several recent studies. Has generally been well tolerated and, in these studies, has been as effective (possibly more effective) as more traditional therapies, including dapsone, sulfasalazine, and azathioprine, with less toxicity.
Adult
500 mg/d PO initially, titrate up to 1000 mg PO bid over 2 mo as tolerated; may increase to 3000 mg/d in occasional patients
Pediatric
600 mg/m2 PO bid; titrate to maximum of 1000 mg PO bid over 2 mo
In combination with either acyclovir or ganciclovir may result in higher levels for both interacting drugs due to competition for renal tubular excretion; aluminum/magnesium present in some antacids, and cholestyramine containing products may decrease absorption, reducing levels (do not administer together); probenecid may increase levels of mycophenolate; salicylates and azathioprine may increase toxicity; may decrease levonorgestrel AUC; may decrease live virus vaccine immune response; when administered in combination with theophylline may increase free fraction levels of theophylline; may reduce blood levels hormones contained in oral contraceptives and could reduce effectiveness
Documented hypersensitivity; active infection (relative); severe cytopenias (relative)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Increases risk for infection (monitor blood count); severe renal impairment (CrCl <25 mL/min) may have increased adverse effects due to increased free MPA; caution in active peptic ulcer disease; incidence of malignancies and lymphoma consistent with that reported for other immunosuppressants (0.9%); commonly causes constipation, nausea, diarrhea, urinary tract infection, and nasopharyngitis; rare reports include interstitial lung disorders, colitis, pancreatitis, intestinal perforation, GI hemorrhage, gastric ulcers, duodenal ulcers, and ileus; do not chew, crush, or cut Myfortic tab; women of childbearing potential must have a negative serum or urine pregnancy test must be completed within one week of beginning MMF and must receive contraceptive counseling and use effective contraception; continue contraception for 6 wk following discontinuing
Systemic steroids
To reduce inflammatory response; however, these are not useful drugs for this disease because of the necessity for long-term usage and the adverse effects. Reserve their use for the severely inflamed eyes that do not readily respond to immunosuppression alone.
Prednisone (Deltasone, Orasone, Meticorten)
Immunosuppressant that may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Adult
1 mg/kg/d PO administered during the first week of therapy; then, the dose is tapered each following week by 10 mg and corticosteroid therapy is discontinued within 8-12 wk
Pediatric
Not established
Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI disease
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Aminosalicylic acid derivative
Used to reduce inflammation.
Sulfasalazine (Azulfidine, En-Tabs)
Sulfonamide derivative with anti-inflammatory properties. Decreases inflammatory response and systemically inhibits prostaglandin synthesis.
Adult
0.5-1 g/d PO; increase qwk to maintenance dose of 2 g/d PO divided bid; increase to 3 g/d if response not satisfactory after 12 wk of treatment; not to exceed 4 g/d
Pediatric
Not established
Decreases effects of iron, digoxin, and folic acid; conversely, increases effect of oral anticoagulants, oral hypoglycemic agents, and methotrexate
Documented hypersensitivity; allergy to sulfa drugs or any component of product; GI or GU obstruction
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in patients with renal or hepatic impairment, blood dyscrasias, or urinary obstruction
Immunomodulators
Interfere with cytokine actions responsible for inflammation. Some anecdotal reports and case series of OCP treatment with anti-TNF-alpha have been described with favorable results.
Infliximab (Remicade)
Chimeric IgG1k monoclonal antibody that neutralizes cytokine TNF-alpha and inhibits its binding to TNF-alpha receptor. Reduces infiltration of inflammatory cells and TNF-alpha production in inflamed areas. Reported in anecdotal case reports
Adult
5 mg/kg as single IV infusion at week 0 and week 2, and then q4wk thereafter; may increase dose up to 10 mg/kg
Pediatric
Administer as in adults
None reported
Documented hypersensitivity to murine proteins or components of formulation; serious clinical infections
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
TNF-alpha modulates cellular immune responses; anti-TNF therapies, such as infliximab, may adversely affect normal immune responses and allow development of superinfections; may be associated with serious infections (some fatal) including reactivation of tuberculosis, sepsis, or opportunistic infections (eg, fungal infections), discontinue if serious infection occurs more cases of lymphoma were observed in TNF alpha-blockers compared to controlled groups; may increase risk of reactivation of tuberculosis in patients with particular granulomatous infections
Etanercept (Enbrel)
A recombinant human TNF-alpha receptor protein fused with Fc portion of IgG1 that binds to TNF-alpha, thereby neutralizing the effects of TNF-alpha. Reported in anecdotal reports and case reports.
Adult
25 mg SC 2 times/wk
Pediatric
<4 years: Not established
4-17 years of age: 0.4 mg/kg SC once qwk; not to exceed 25 mg/dose
>17 years: Administer as in adults
Do not administer within 3 mo of live virus vaccines (eg, MMR)
Documented hypersensitivity; sepsis; concurrent live virus vaccines
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in impaired renal function and asthma; increases risk of serious infections, including infections that may result in hospitalization or death; may increase risk of opportunistic infections (eg, tuberculosis [TB], invasive fungal), if serious infections develop, discontinued therapy; possible adverse effects include injection site pain, redness and swelling at injection site, and headaches; rare cases of lupus-like symptoms and heart failure have been reported (discontinue treatment if symptoms develop)
Monoclonal antibodies
Found to be effective for OCP in uncontrolled small studies.
Daclizumab (Zenapax)
Humanized monoclonal antibody that specifically binds to and blocks interleukin-2 (IL-2) receptor on surface of activated T cells.
Adult
1 mg/kg IV q2wk; infuse IV over 15 min
Pediatric
Not established; suggested to administer as in adults
None reported higher rate of serious infections and neutropenia are possible when coadministered with antilymphocyte antibody therapy
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Manage patients receiving the drug in facilities with adequate supportive medical resources; severe, acute (onset within 24 h) hypersensitivity reactions including anaphylaxis have been observed with first exposure and upon re-exposure; anaphylaxis characterized by hypotension, bronchospasm, wheezing, laryngeal edema, pulmonary edema, cyanosis, hypoxia, respiratory arrest, cardiac arrhythmia, cardiac arrest, peripheral edema, loss of consciousness, fever, rash, urticaria, diaphoresis, pruritus, and/or injection site reactions, as well as cytokine release syndrome, have been reported; commonly reported adverse effects include psoriasiform skin rashes, lymphadenopathy, mild peripheral edema, and infections; studies in heart transplant recipients have shown increased mortality related to increased severe infection incidence
Rituximab (Rituxan)
Genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of B lymphocytes.
Adult
375 mg/m2 IV qwk for 4 doses
Administer methylprednisolone 100 mg IV (or its equivalent) 30 min before each infusion to reduce infusion related reactions
Do not exceed infusion rate of 50 mg/h initially; if hypersensitivity or infusion-related reactions do not occur, may escalate infusion rate by 50 mg/h increments q30min; not to exceed 400 mg/h
Pediatric
Not established
Coadministration with cisplatin is known to cause severe renal toxicity including acute renal failure; may interfere with immune response to live virus vaccine (MMR) and reduce efficacy (do not administer within 3 months of vaccine)
Documented hypersensitivity; IgE mediated reaction to murine proteins; vaccination with live virus vaccines is not recommended; active infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Severe infusion reactions during the first infusion with time to onset of 30-120 min; urticaria, hypotension, angioedema, hypoxia, or bronchospasm, and may require interruption of infusion; complete blood cell (CBC) counts and platelet counts should be obtained at regular intervals and more frequently in patients who develop cytopenias; duration of cytopenias can extend well beyond the treatment period
Immunoglobulins
Used in cases resistant to conventional treatment.
Immune globulin intravenous (Gamimune, Gammagard, Sandoglobulin, Gammar-P)
Contains the pooled immunoglobulin G (IgG) immunoglobulins from the plasma of approximately a thousand or more blood donors. Acts by modulation of complement activation; suppression of idiotypic antibodies; saturation of Fc receptors on macrophages; and suppression of various inflammatory mediators, including cytokines, chemokines, and metalloproteinases.
Adult
2-3 g/kg/cycle IV infused over 3 d in equally divided doses; repeat q2wk
Increase dose interval when conjunctival inflammation subsides to q3wk, then q4wk, q6wk, q8wk, q12wk, q14wk, and finally q16wk, discontinue after second 16 wk dosage regimen
Pediatric
Not established
Globulin preparation may interfere with immune response to live virus vaccine (MMR) and reduce efficacy (do not administer within 3 months of vaccine)
Documented hypersensitivity; IgA deficiency
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Check serum IgA before IVIG (use an IgA-depleted product if deficient, eg, Gammagard S/D); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 d postinfusion); increases risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, and preexisting kidney disease; lab result changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia
More on Cicatricial Pemphigoid |
| Overview: Cicatricial Pemphigoid |
| Differential Diagnoses & Workup: Cicatricial Pemphigoid |
 Treatment & Medication: Cicatricial Pemphigoid |
| Follow-up: Cicatricial Pemphigoid |
| Multimedia: Cicatricial Pemphigoid |
| References |
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References
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Further Reading
Keywords
cicatricial pemphigoid, ocular cicatricial pemphigoid, OCP, mucous membrane pemphigoid, MMP, chronic cicatrizing conjunctivitis
