Pemphigus penicillamine

Kind P, Goerz G, Gleichmann E, Plewig G. Penicillamin induzierter Pemphigus. [Penicillamine-induced pemphigus.] Hautarzt 1987 38(9) 548-52. 

Pemphigus Flaccid bullae, chest Present or absent Penicillamine,captopril, piroxicam, penicillin, rifampin Supportive0... 

Nitrofurantion D-Penicillamine Peripheral neuritis Autoimmunity drug-induced SLE, myasthenia gravis, pemphigus, glomerulonephritis, Goodpasture s disease... 

Although rare, cases of renal lupus syndrome and pemphigus blisters have also been reported as a consequence of D-penicillamine-induced immune complexes (Ntoso et al., 1986 Bigazzi, 1988), as well as with other drugs. With renal lupus syndrome, secondary glomerulonephritis may result if granular IgG antibodies are produced and deposited on the basement membranes. In patients with pemphigus blisters, autoantibodies to the intercellular substance of the skin have been recovered from the sera, and dermal biopsies have demonstrated intracellular deposits or... 

Hepatotoxicity Penicillamine has been associated with a mild elevation of hepatic enzymes that usually returns to normal even with continuation of the drug. Autoimmune syndromes Autoimmune syndromes that may be caused by penicillamine include polymyositis, diffuse alveolitis and dermatomyositis, Goodpasture s syndrome, myasthenic syndrome, pemphigus, and obliterative bronchiolitis. 

In 20-25% of cases, side effects are observed, depending mainly on the dose (hypersensitivity reactions, aphthous lesions, arthralgia, nausea, fever). All in all, treatment of Wilson s disease with penicillamine is considered to be successful and safe. If jrenicill-amine is not well tolerated or if serious side effects are observed (e.g. kidney or bone-marrow damage, polyneuropathy, pemphigus), treatment must be discontinued. Penicillamine usually causes pyridoxin deficiency, so that substitution (25—40 mg/day) is recommended, particularly as chronic liver damage also leads to vitamin Bg deficiency. If necessary, electrolytes and trace elements also have to be substituted. 

Another patient had a pemphigus foliaceus-like eruption on three different occasions, in association with penicillamine, auranofin, and bucillamine (12). 

A 53-year-old woman with rheumatoid arthritis who had reacted to D-penicillamine treatment by developing myasthenia gravis was given gold instead and 12 months later developed pemphigus vulgaris (60). 

Ciompi ML, Marchetti G, Bazzichi L, Puccetti L, AgeUi M. D-penicillamine and gold salt treatments were comphcated by myasthenia and pemphigus, respectively, in the same patient with rheumatoid arthritis. Rheumatol Int 1995 15(3) 95-7. 

Hypersensitivity reactions are frequent early in a course of penicillamine, with urticarial or maculopapular rashes, fever, and lymphadenopathy. Cross-allergy to penicillin can occur. In addition, the use of penicillamine can be complicated by a unique variety of often serious autoimmune reactions, involving the skin, kidneys, liver, lungs, muscles, or other organs. Proteinuria is found in more than 10% of patients and sometimes develops into the nephrotic syndrome. Pemphigus, myasthenia gravis, polymyositis, or a lupus-like syndrome occur in smaller percentages. 

Rhinitis, bronchospasm, and asthma can occur as a manifestation of hypersensitivity to penicillamine (SEDA-5, 248) (61-63) and rarely of the Churg-Strauss syndrome (64). Rhinitis can also be a symptom of peni-ciUamine-induced pemphigus (65). In one patient a large pulmonary cyst developed concomitantly with skin lesions characteristic of the use of large doses of penicillamine (66). Microscopic derangement of the elastic fibers predominated. Although the frequency is uncertain, penicillamine can be associated with recurrent respiratory tract infections, that is secondary to IgA deficiency (67,68) or as part of the yellow nail syndrome (SEDA-9, 223). 

Cheilosis has also been reported (178). Oral lesions in patients using penicillamine may be due to pemphigus, cicatricial pemphigoid, or lichen planus, even in the absence of lesions outside the oral cavity. In 56 consecutive patients taking penicillamine, oral lichen planus was found in as many as seven (179). Penicillamine-induced cicatricial pemphigoid can be associated with oral ulcers as well as lesions of the esophagus, and stenosis can develop. 

Penicillamine can cause localized scleroderma (also known as morphea), which has been reviewed (257). Bullous lesions can occur in scleroderma (localized, generalized, or systemic), and this highlights the diagnostic problems in such patients (258). In one of the four case histories presented in this paper, the bullous eruption, in a patient taking penicillamine for systemic sclerosis, was diagnosed as penicillamine-induced pemphigus foliaceus. 

Penicillamine has epidermotropic properties and accumulates in the skin. There are several possible mechanisms involved in penicillamine-induced pemphigus (SED-12, 544) ... 

Penicillamine-induced pemphigus can pose diagnostic difficulties, for example because it can present as a nonspecific rash, seborrheic dermatitis, erythema annulare (311), isolated stomatitis, or even rhinitis (65). Because of the friability of the superficial blisters, the bullous nature of pemphigus erythematosus and pemphigus folia-ceus may be overlooked. 

Since beta-lactam antibiotics also appear to be associated with pemphigus, especially ampicillin and amoxicillin, an earlier hypothesis (SEDA-5, 244) that this (and perhaps other reactions) to beta-lactam antibiotics may in fact be induced by the hydrolytic metabolite penicillamine has received attention (280,283). 

Ulcerative lesions of the vagina can occur in patients taking penicillamine, as a manifestation of pemphigus or cicatricial pemphigoid, or following impaired collagen synthesis (SED-8, 533) (315). 

A 47-year-old woman developed concurrent pemphigus and myasthenia gravis (with ptosis and diplopia), apparently induced by penicillamine (500 mg/day for rheumatoid arthritis) (376). 

Knezevic W, Mastaglia FL, Quintner J, Zilko PJ. Guillain-Barre syndrome and pemphigus foliaceus associated with D-penicillamine therapy. Aust NZ J Med 1984 14(l) 50-2. 

Jan V, Callens A, Machet L, Machet MC, Lorette G, VaUlant L. Pemphigus polymyosite et myasthenie induites par la D-penicillamine. [D-peniciUamine-induced pemphigus, polymyositis and myasthenia.] Ann Dermatol Venereol 1999 126(2) 153-6. 

Penas PF, Buezo GF, Carvajal I, Dauden E, Lopez A, Diaz LA. D-penicillamine-induced pemphigus foliaceus with autoantibodies to desmoglein-1 in a patient with mixed connective tissue disease. J Am Acad Dermatol 1997 37(l) 121-3. 

McGovern TW, Bennion SD. Diffuse blisters and erosions in a patient with limited scleroderma. Penicillamine-induced pemphigus foliaceus (PIPF). Arch Dermatol 1997 133(4) 501. 

Verret JL, Avene IM, Smulevici A, Esparbes M. Les pemphigus induits par la penicillamine a propos de trois cas. J Agregres 1983 16 209. 

Hashimoto K, Singer K, Lazarus GS. Penicillamine-induced pemphigus. Immunoglobulin from this patient induces plasminogen activator synthesis by human epidermal cells in culture mechanism for acantholysis in pemphigus. Arch Dermatol 1984 120(6) 762-4. 

Bahmer FA, Bambauer R, Stenger D. Penicillamine-induced pemphigus foliaceus-hke dermatosis. A case with unusual features, successfully treated by plasmapheresis. Arch Dermatol 1985 121(5) 665-8. 

Willemsen MJ, De Coninck AL, De Raeve LE, Roseeuw DI. Penicillamine-induced pemphigus erythematosus. Int J Dermatol 1990 29(3) 193-7. 

Rasmussen HB, Jepsen LV, Brandrup F. Penicillamine-induced bullous pemphigoid with pemphigus-like antibodies. J Cutan Pathol 1989 16(3) 154-7. 

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