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Linear IgA bullous dermatosis: Successful treatment with tetracycline and nicotinamide
Journal of the American Academy of Dermatology
498 Brief communications
Linear IgA bullous dermatosis: Successful treatment with tetracycline and nicotinamide Danita Peoples, MD, and David P. Fivenson, MD Detroit, Michigan Tetracycline combined with nicotinamide (niacinamide) has been reported as effective therapy for bullous pemphigoid. 1 Nicotinamide alone or in combination with tetracycline has also been reported to be as effective in the treatment of dermatitis herpetiformis, necrobiosis lipoidica diabeticorurn, generalized granuloma annulare, polymorphous light eruption, aphthous stomatitis, pellagra, Hartnup disease, and erythema elevatum diutinum.2-8 We present a patient with linear IgA bullous dermatitis who has been successfully treated with the combination of tetracycline and nicotinamide. CASE REPORT A 69-year-old white woman with chronic lymphocytic leukemia (B-cell type) had a pruritic, annular, erythematous, papular eruption of the periumbilical region, posterior trunk, groins, axillae, and arms. Tense bullae developed at the periphery of the erythematous areas as well as on normal-appearing skin (Fig. 1). Histologic examination of lesional skin was nondiagnostic and no specific cell population was identified in die tissue or blister cavity. Direct immunofluorescence of perilesional skin demonstrated a 3+ linear deposition of IgA along the basement membrane zone. Indirect immunofluorescence was negative for circulating antibasement membrane zone antibodies of IgG or IgA classes (tested on monkey esophagus). The patient was initially treated with prednisone (60 mg/day) for I week with moderate improvement. This therapy was discontinued because of a history of gastric ulcers. Tetracycline (2000 mg/day) and niacinamide (1500 mg/day) was then begun and within 3 weeks her skin had completely cleared. Treatment was temporarily interrupted after clearing because of mild gastric distress. After therapy was discontinued, the eruption rapidly recurred on the hands and the middle and upper back. Tetracycline and niacinamide at doses of 1500 mg/day and 900 mgjday, respectively, were started again and were
From the Department of Dermatology, Henry Ford Hospital. No reprints available.
16/54/33903
Fig. 1. A, Tense vesicles and bullae on the thumb that recur whenever tetracycline and nicotinamide therapy is interrupted. B, Polycyclic, urticarial plaques on the abdomen, many with central vesicles.
more tolerable; complete clearing was again achieved. The episodic nature of the chemotherapeutic regimen used to treat her chronic lymphocytic leukemia has forced periodic interruption in treatment of her skin condition. Each time, however, restarting the tetracycline and nicotinamide therapy has rapidly brought about clearing. DISCUSSION
We present a patient with linear IgA bullous dermatosis associated with chronic lymphocytic leuke-
Volume 26 Number 3 March 1992
Brief communications
mia who responded dramatically to tetracycline and nicotinamide therapy. She has been successfully treated without long-term systemic steroids, thereby avoiding complications that an elderly patient may be predisposed to have. The proposed mechanism of action for tetracycline and nicotinamide in autoimmune bullous diseases may include their ability to inhibit neutrophil and/ or eosinophil chemotaxis/secretion, inhibit histamine release, inhibit phosphodiesterase, and suppress lymphocyte transformation. I, 9-13 Which of these is most likely in our patient is speculative. However, effects on lymphocyte transformation with a resultant decrease in IgA anti-basement membrane zone antibodies and/or decreases in neutrophil chemotaxis seem to be the most probable mechanisms of action for the therapeutic response. REFERENCES I. Berk MA, Lorincz AL. The treatment of bullous pemphigoid with tetracycline and niacinamide. Arch Dermatol 1986;122:670-4. 2. Johnson HH, Binkley GW. Nicotinic acid therapy of dermatitis herpetiformis. J Invest Dermatol 1949;14:233-8. 3. Handfield-Jones S, Jones S, Peachey R. High dose nicotinamide in the treatment of necrobiosis lipoidica. Br J DermatoI1988;118:693-6.
499
4. Ma A, Medenica M. Response of generalized granuloma annulare to high-dose niacinamide. Arch Dermatol 1983;119:836-9. 5. Neumann R, Rappold E, Pohl-Markl H. Treatment of polymorphous light eruption with nicotinamide: a pilot study. Br J DermatolI986;115:77-80. 6. Comaish JS, Felix RH, McGrath H. Topically applied niacinamide in isoniazid-induced pellagra. Arch Dermatol 1976;112:70-2. 7. Barthelemy H, Chouvet B, Cambazard F. Skin and mucosal manifestations in vitamin deficiency. J AM ACAD DERMATOL 1986;15:1263-74. 8. Kohler IK, Lorincz AL. Erythema elevatum diutinum treated with niacinamide and tetracycline. Arch Dermatol 1980;116:693-5. 9. Cohen BM. Niacinamide-theophylline compound eRC-C144). I. Human absorption and blood level studies. J Asthma Res 1966;4:75-9. 10. Cohen BM. A niacinamide-theophylline compound (RCC-144). II. Clinical spyrometric effects. J Asthma Res 1966;4:81-7. 11. Burger DR, Vandenbark AA, Doyle D, et al. Nicotinamide: suppression of lymphocyte transformation with a component identified in human transfer factor. J Immunol 1976;117:797-801. 12. Wu KI, Bacon RA, Al-Mahrouq HA, et al. Nicotinamide as a rapid-acting inhibitor of renal brush-border phosphate transport. Am J PhysioI1988;15-21. 13. Bekier E, Masinski C. Antihistaminic action of nicotinamide. Agents Action 1974;4:196.
Papuloerythroderrna (Ofuji): Two additional cases and review of the literature Guido Nazzari, MD,a Franco Crovato, MD,a and Anna Nigro, MDb
Chiavari and Genoa, Italy Since the first report of papuloerythroderma in
1984 by 0 fuji et aL, I there have been 35 cases pub-
lished in the Japanese literature. 2 Thus far only five cases have been published from Europe. 3-7 We report the first two cases observed in Italy.
CASE REPORTS Case 1 A 76-year-old man had a widespread pruritic eruption characterized by lichen planus-like erythematous papFrom the Divisions of Dermatology, Chiavari-Lavagna Hospital, Chiavari,n and S. Martino Hospital, Genoa. b No repri nts available.
16/54/33908
ules of 1 month duration. The papules coalesced into large sheets (Fig. I). The antecubital and popliteal fossae, face, scalp, palms, and soles were normal. Results of routine laboratory tests were negative except for eosinophilia, 2310 cells/mm3 , and a mild elevation of serum 19B, 415
Dim!.
A skin biopsy specimen showed a dense lymphohistiocytic infiltrate with eosinophils in the papillary dermis chiefly around the blood vessels. Direct immunofluorescence was negative. Treatment with topical fluocinonide produced moderate improvement in his pruritus but the lesions remained unchanged. Oral prednisone, 50 mg daily, was started with resolution of the lesions after 18 days of therapy. The eosinophilia also resolved. There was no relapse after withdrawal of prednisone.
498 Brief communications
Linear IgA bullous dermatosis: Successful treatment with tetracycline and nicotinamide Danita Peoples, MD, and David P. Fivenson, MD Detroit, Michigan Tetracycline combined with nicotinamide (niacinamide) has been reported as effective therapy for bullous pemphigoid. 1 Nicotinamide alone or in combination with tetracycline has also been reported to be as effective in the treatment of dermatitis herpetiformis, necrobiosis lipoidica diabeticorurn, generalized granuloma annulare, polymorphous light eruption, aphthous stomatitis, pellagra, Hartnup disease, and erythema elevatum diutinum.2-8 We present a patient with linear IgA bullous dermatitis who has been successfully treated with the combination of tetracycline and nicotinamide. CASE REPORT A 69-year-old white woman with chronic lymphocytic leukemia (B-cell type) had a pruritic, annular, erythematous, papular eruption of the periumbilical region, posterior trunk, groins, axillae, and arms. Tense bullae developed at the periphery of the erythematous areas as well as on normal-appearing skin (Fig. 1). Histologic examination of lesional skin was nondiagnostic and no specific cell population was identified in die tissue or blister cavity. Direct immunofluorescence of perilesional skin demonstrated a 3+ linear deposition of IgA along the basement membrane zone. Indirect immunofluorescence was negative for circulating antibasement membrane zone antibodies of IgG or IgA classes (tested on monkey esophagus). The patient was initially treated with prednisone (60 mg/day) for I week with moderate improvement. This therapy was discontinued because of a history of gastric ulcers. Tetracycline (2000 mg/day) and niacinamide (1500 mg/day) was then begun and within 3 weeks her skin had completely cleared. Treatment was temporarily interrupted after clearing because of mild gastric distress. After therapy was discontinued, the eruption rapidly recurred on the hands and the middle and upper back. Tetracycline and niacinamide at doses of 1500 mg/day and 900 mgjday, respectively, were started again and were
From the Department of Dermatology, Henry Ford Hospital. No reprints available.
16/54/33903
Fig. 1. A, Tense vesicles and bullae on the thumb that recur whenever tetracycline and nicotinamide therapy is interrupted. B, Polycyclic, urticarial plaques on the abdomen, many with central vesicles.
more tolerable; complete clearing was again achieved. The episodic nature of the chemotherapeutic regimen used to treat her chronic lymphocytic leukemia has forced periodic interruption in treatment of her skin condition. Each time, however, restarting the tetracycline and nicotinamide therapy has rapidly brought about clearing. DISCUSSION
We present a patient with linear IgA bullous dermatosis associated with chronic lymphocytic leuke-
Volume 26 Number 3 March 1992
Brief communications
mia who responded dramatically to tetracycline and nicotinamide therapy. She has been successfully treated without long-term systemic steroids, thereby avoiding complications that an elderly patient may be predisposed to have. The proposed mechanism of action for tetracycline and nicotinamide in autoimmune bullous diseases may include their ability to inhibit neutrophil and/ or eosinophil chemotaxis/secretion, inhibit histamine release, inhibit phosphodiesterase, and suppress lymphocyte transformation. I, 9-13 Which of these is most likely in our patient is speculative. However, effects on lymphocyte transformation with a resultant decrease in IgA anti-basement membrane zone antibodies and/or decreases in neutrophil chemotaxis seem to be the most probable mechanisms of action for the therapeutic response. REFERENCES I. Berk MA, Lorincz AL. The treatment of bullous pemphigoid with tetracycline and niacinamide. Arch Dermatol 1986;122:670-4. 2. Johnson HH, Binkley GW. Nicotinic acid therapy of dermatitis herpetiformis. J Invest Dermatol 1949;14:233-8. 3. Handfield-Jones S, Jones S, Peachey R. High dose nicotinamide in the treatment of necrobiosis lipoidica. Br J DermatoI1988;118:693-6.
499
4. Ma A, Medenica M. Response of generalized granuloma annulare to high-dose niacinamide. Arch Dermatol 1983;119:836-9. 5. Neumann R, Rappold E, Pohl-Markl H. Treatment of polymorphous light eruption with nicotinamide: a pilot study. Br J DermatolI986;115:77-80. 6. Comaish JS, Felix RH, McGrath H. Topically applied niacinamide in isoniazid-induced pellagra. Arch Dermatol 1976;112:70-2. 7. Barthelemy H, Chouvet B, Cambazard F. Skin and mucosal manifestations in vitamin deficiency. J AM ACAD DERMATOL 1986;15:1263-74. 8. Kohler IK, Lorincz AL. Erythema elevatum diutinum treated with niacinamide and tetracycline. Arch Dermatol 1980;116:693-5. 9. Cohen BM. Niacinamide-theophylline compound eRC-C144). I. Human absorption and blood level studies. J Asthma Res 1966;4:75-9. 10. Cohen BM. A niacinamide-theophylline compound (RCC-144). II. Clinical spyrometric effects. J Asthma Res 1966;4:81-7. 11. Burger DR, Vandenbark AA, Doyle D, et al. Nicotinamide: suppression of lymphocyte transformation with a component identified in human transfer factor. J Immunol 1976;117:797-801. 12. Wu KI, Bacon RA, Al-Mahrouq HA, et al. Nicotinamide as a rapid-acting inhibitor of renal brush-border phosphate transport. Am J PhysioI1988;15-21. 13. Bekier E, Masinski C. Antihistaminic action of nicotinamide. Agents Action 1974;4:196.
Papuloerythroderrna (Ofuji): Two additional cases and review of the literature Guido Nazzari, MD,a Franco Crovato, MD,a and Anna Nigro, MDb
Chiavari and Genoa, Italy Since the first report of papuloerythroderma in
1984 by 0 fuji et aL, I there have been 35 cases pub-
lished in the Japanese literature. 2 Thus far only five cases have been published from Europe. 3-7 We report the first two cases observed in Italy.
CASE REPORTS Case 1 A 76-year-old man had a widespread pruritic eruption characterized by lichen planus-like erythematous papFrom the Divisions of Dermatology, Chiavari-Lavagna Hospital, Chiavari,n and S. Martino Hospital, Genoa. b No repri nts available.
16/54/33908
ules of 1 month duration. The papules coalesced into large sheets (Fig. I). The antecubital and popliteal fossae, face, scalp, palms, and soles were normal. Results of routine laboratory tests were negative except for eosinophilia, 2310 cells/mm3 , and a mild elevation of serum 19B, 415
Dim!.
A skin biopsy specimen showed a dense lymphohistiocytic infiltrate with eosinophils in the papillary dermis chiefly around the blood vessels. Direct immunofluorescence was negative. Treatment with topical fluocinonide produced moderate improvement in his pruritus but the lesions remained unchanged. Oral prednisone, 50 mg daily, was started with resolution of the lesions after 18 days of therapy. The eosinophilia also resolved. There was no relapse after withdrawal of prednisone.