Archives for
Arch. Derra. Res. 258, 81-83 (1977)
ical arcn Deseermat•.log 0 by Springer-Verlag 1977
Archives for Dermatological Research Letters Melphalan-Induced Melanonychia Striata Paolo Malacarne and Giorgio Zavagli Institute for MedicalClinic(Head: Prof. A. Baserga),Universityof Ferrara, 1-44100 Ferrara, Italy
Introduction
In the treatment of neoplastic affections, also the skin is involved by prolonged antimitotic drug administration. Atrophy patterns of a much higher degree than that expected from the patient's age (Baserga, 1956), as well as cutaneous dyschromias (mostly hyperpigmentations and zonal melanodermas) may be observed. Under such conditions also skin appendages, such as hair and nails, are affected. Hair shows alterations varying from brittleness to zonal or diffuse alopecia. On the other hand, during or after chemotherapeutic treatment nails may undergo: (a) a "pseudoleukonychia totalis" picture, consisting of marked plate pallor; (b) the haemorrhagic nail bed disease, due to more or less evident haemorrhages occurring within the hyponychium or between hyponychium and lamina; both such patterns (a) and (b) may be considered as a local expression of erythrocyte and drug-depressed platelet production respectively; (c) a curtailing or the complete disappearance Of the lunula, as well as onychoatrophy and onychohypotrophy characterized by reduced plate thickness and/or free edge irregularities, which constitute a direct expression of the drug-caused nail matrix damage; (d) transversal onychoatrophy (or "Beau's striations"), observed mostly after short and intense antineoplastic treatment; (e) melanonychia, that is a dark nail bed pigmentation caused by a zonal numerical increase of melanin granules present in the basal layer melanocytes. Melanonychia has also been observed in cases of malaria, syphilis, gastrointestinal disorders, adrenocortical insufficiencies (De Nicola et al., 1974), as well as in gold, arsenic, and phenolphthalein poisoning. In chemotherapeutically treated patients most observations related melanonychia with cyclophosphamide (Harrison and Wood, 1972; Shah et al., 1975), although bleomycin (Higuchi, 1969; Ichikawa,
82
P. Malacarne and G. Zavagli
1970), 5-fluoro-uracil (Moore and Meiselbaugh, 1975). Also adriamycin (Rothberg, 1974; Priestman and James, 1975) may cause such changes. Similarly, melphalan has b e e n considered as a possible cause of melanonychia, even if the only patient, reported by Shah et al. (1975), had b e e n previously administered cyclophosphamide. Thus to melphalan only the melanonychia m a i n t e n a n c e role might be attributed. A case admitted into our Institute seems to suggest that melphalan by itself can induce the onset of melanonychia.
C a s e Report A 69-year-old country-woman from Ferrara (Italy), who had been in good health (except for an appendectomy at the age of 32 years) up to July 1974, when she noted the onset of a painless progressive skin swellingjust above the rigth medial malleolus, associated with lymph node enlargement. Symptoms of general involvement, such as anorexia, weight loss, easy sweating, malaise, intermittent mild fever, and dyspnoea were present. After a few months, owing to further lymph node mass enlargement associated with marked worsening of the general conditions, the patient underwent surgical intervention (October 7th, 1975). The removed mass evidenced the existence of a melanosarcoma, associated with metastatic lymph node involvement. Therefore, 10 days after the intervention, therapy with melphalan was initiated at daily doses of 5 rag, which the patient kept on taking until her admission (December 9th, 1975) into our Institute owing to the onset of severe anaemia. On that occasion, the patient evidenced marked pallor associated with tachycardia, dyspnoea, and on auscultation a mid-systolic soft murmur of faint intensity was appreciable. Both finger and toe nails presented an evident "melanonychia striata" picture, more marked on both forefingers (Fig. 1). Laboratory investigations confirmed a high degree anaemia (haemoglobin 4.1 g%; RBC 1.35 x 106/mm3), associated with haematocrit 18%, reticulocyte count 0.2%, WBC 2.4 x 103/mm3, platelets 15 x 103/ram3. Thus, after the opportune investigations, the diagnosis of antimitotic agent-induced pancytopaenia was stated. Consequently melphalan administration was promptly stopped, and replaced with blood transfusions. After a short time the haemopoietic balance improved in a significant fashion: the haemoglobin level rose to 12.2 g%, RBC to 4.21 x 106/mm3, but a leukopaenic condition did persist (WBC 2.7 x 103/mm3). The bone marrow punction evidenced, however, a satisfactory recovery, so that the patient could be discharged, with the warning not to take any drug because of the persistent leucopaenia. The patient, who was living elsewhere, underwent no further controls at our out-patient service. On April 26th of the current year the patient was admitted into the dermatological department of Ferrara, owing to a cutaneous metastatic relapse at the affected leg. On that occasion it could be observed that the patient's nails had lost their dark pigmentation, while only a very slight "melanonychia striata" picture did persist at the middle finger of her right hand.
Fig. 1
Melphalan-Induced Melanonychia Striata
83
Discussion The disappearance of the present patient's melanonychia some months after the stopping of melphalan administration seems to closely relate such dark pigmentation to the antimitotic agent, and not to the underlying affection. Thus melphalan administration can, by itself, cause the onset of melanonychia. The mechanism of chemotherapeutic, drug-induced melanonychia may approach that of likewise caused melanoderma, although these patterns fail to coexist constantly in the same patient. The following explanations have been advanced: (a) an eventual selective hormone-suppressive action of the drug can release excessive amounts of MSH from the posterior pituitary (Priestman and James, 1975); (b) the A C T H molecule may undergo drug-mediated modifications, so that a melanocytestimulating component is released: this would occur mostly with busulphan (Scapoli et al., 1975). The mechanism of chemotherapeutic agent-induced melanonychia is still uncertain: Moore and Meiselbaugh (1975) have suggested that such drugs suppress not only the adrenal function, but that of other endocrine glands as well. The presence of adrenal insufficiency has not, however, been hitherto supported by clinical or laboratory findings. Also in the present patient the authors failed to detect such a disorder. Whatever the mechanism of antimitotic drug-induced melanonychia may be, such aspect may rightly be included among the numerous patterns of cell dysplasias, due to chemotherapeutic drugs.
References Baserga, A.: Primi lineamenti di patologia arigenerativa. Min. med. 37, 247 (1956) De Nicola, P., Morsiani, M., Zavagli, G.: Nail diseases in internal medicine. 1st edn., p. 54. Springfield: Charles C. Thomas 1974 Harrison, B. M., Wood, C. B. S.: Cyclophosphamide and pigmentation. Brit. med. J. 1972 II, 352 Higuchi, K.: Chemotherapy of skin cancer with bleomycin. 6. intern. Congress of Chemotherapy, Tokyo, August 10-15, 1969 Ichikawa, T.: Discovery of clinical effects of bleomycin against squamous cell carcinoma and further development of its research. 10. intern. Cancer Congress, Houston, May 22-29, 1970 Moore, G., Meiselbaugh, D.: Hyperpigmentation after cancer chemotherapy. Lancet 1975 II, 128 Priestman, T. J., James, K. W.: Adriamycin and longitudinal pigmented banding of fingernails. Lancet 1975 I, 1337 Rothberg, H.: Adriamycin toxicity: unusual melanotic reaction. Cancer Chemother. Abstr. 58, 749 (1974) Scapoli, G. L., Bertocco, S., Spanedda, R., Bariani, L.: Iperpigmentazione da busulfano in corso di trattamento di leucemia mieloide cronica. Riforma med. 89, 149 (1975) Shah, P. C., Rao, K. R. P., Patel, A.R.: Cyclophosphamide-induced nail pigmentation. Lancet 1975 II, 548 Received December 18, 1976
Arch. Derra. Res. 258, 81-83 (1977)
ical arcn Deseermat•.log 0 by Springer-Verlag 1977
Archives for Dermatological Research Letters Melphalan-Induced Melanonychia Striata Paolo Malacarne and Giorgio Zavagli Institute for MedicalClinic(Head: Prof. A. Baserga),Universityof Ferrara, 1-44100 Ferrara, Italy
Introduction
In the treatment of neoplastic affections, also the skin is involved by prolonged antimitotic drug administration. Atrophy patterns of a much higher degree than that expected from the patient's age (Baserga, 1956), as well as cutaneous dyschromias (mostly hyperpigmentations and zonal melanodermas) may be observed. Under such conditions also skin appendages, such as hair and nails, are affected. Hair shows alterations varying from brittleness to zonal or diffuse alopecia. On the other hand, during or after chemotherapeutic treatment nails may undergo: (a) a "pseudoleukonychia totalis" picture, consisting of marked plate pallor; (b) the haemorrhagic nail bed disease, due to more or less evident haemorrhages occurring within the hyponychium or between hyponychium and lamina; both such patterns (a) and (b) may be considered as a local expression of erythrocyte and drug-depressed platelet production respectively; (c) a curtailing or the complete disappearance Of the lunula, as well as onychoatrophy and onychohypotrophy characterized by reduced plate thickness and/or free edge irregularities, which constitute a direct expression of the drug-caused nail matrix damage; (d) transversal onychoatrophy (or "Beau's striations"), observed mostly after short and intense antineoplastic treatment; (e) melanonychia, that is a dark nail bed pigmentation caused by a zonal numerical increase of melanin granules present in the basal layer melanocytes. Melanonychia has also been observed in cases of malaria, syphilis, gastrointestinal disorders, adrenocortical insufficiencies (De Nicola et al., 1974), as well as in gold, arsenic, and phenolphthalein poisoning. In chemotherapeutically treated patients most observations related melanonychia with cyclophosphamide (Harrison and Wood, 1972; Shah et al., 1975), although bleomycin (Higuchi, 1969; Ichikawa,
82
P. Malacarne and G. Zavagli
1970), 5-fluoro-uracil (Moore and Meiselbaugh, 1975). Also adriamycin (Rothberg, 1974; Priestman and James, 1975) may cause such changes. Similarly, melphalan has b e e n considered as a possible cause of melanonychia, even if the only patient, reported by Shah et al. (1975), had b e e n previously administered cyclophosphamide. Thus to melphalan only the melanonychia m a i n t e n a n c e role might be attributed. A case admitted into our Institute seems to suggest that melphalan by itself can induce the onset of melanonychia.
C a s e Report A 69-year-old country-woman from Ferrara (Italy), who had been in good health (except for an appendectomy at the age of 32 years) up to July 1974, when she noted the onset of a painless progressive skin swellingjust above the rigth medial malleolus, associated with lymph node enlargement. Symptoms of general involvement, such as anorexia, weight loss, easy sweating, malaise, intermittent mild fever, and dyspnoea were present. After a few months, owing to further lymph node mass enlargement associated with marked worsening of the general conditions, the patient underwent surgical intervention (October 7th, 1975). The removed mass evidenced the existence of a melanosarcoma, associated with metastatic lymph node involvement. Therefore, 10 days after the intervention, therapy with melphalan was initiated at daily doses of 5 rag, which the patient kept on taking until her admission (December 9th, 1975) into our Institute owing to the onset of severe anaemia. On that occasion, the patient evidenced marked pallor associated with tachycardia, dyspnoea, and on auscultation a mid-systolic soft murmur of faint intensity was appreciable. Both finger and toe nails presented an evident "melanonychia striata" picture, more marked on both forefingers (Fig. 1). Laboratory investigations confirmed a high degree anaemia (haemoglobin 4.1 g%; RBC 1.35 x 106/mm3), associated with haematocrit 18%, reticulocyte count 0.2%, WBC 2.4 x 103/mm3, platelets 15 x 103/ram3. Thus, after the opportune investigations, the diagnosis of antimitotic agent-induced pancytopaenia was stated. Consequently melphalan administration was promptly stopped, and replaced with blood transfusions. After a short time the haemopoietic balance improved in a significant fashion: the haemoglobin level rose to 12.2 g%, RBC to 4.21 x 106/mm3, but a leukopaenic condition did persist (WBC 2.7 x 103/mm3). The bone marrow punction evidenced, however, a satisfactory recovery, so that the patient could be discharged, with the warning not to take any drug because of the persistent leucopaenia. The patient, who was living elsewhere, underwent no further controls at our out-patient service. On April 26th of the current year the patient was admitted into the dermatological department of Ferrara, owing to a cutaneous metastatic relapse at the affected leg. On that occasion it could be observed that the patient's nails had lost their dark pigmentation, while only a very slight "melanonychia striata" picture did persist at the middle finger of her right hand.
Fig. 1
Melphalan-Induced Melanonychia Striata
83
Discussion The disappearance of the present patient's melanonychia some months after the stopping of melphalan administration seems to closely relate such dark pigmentation to the antimitotic agent, and not to the underlying affection. Thus melphalan administration can, by itself, cause the onset of melanonychia. The mechanism of chemotherapeutic, drug-induced melanonychia may approach that of likewise caused melanoderma, although these patterns fail to coexist constantly in the same patient. The following explanations have been advanced: (a) an eventual selective hormone-suppressive action of the drug can release excessive amounts of MSH from the posterior pituitary (Priestman and James, 1975); (b) the A C T H molecule may undergo drug-mediated modifications, so that a melanocytestimulating component is released: this would occur mostly with busulphan (Scapoli et al., 1975). The mechanism of chemotherapeutic agent-induced melanonychia is still uncertain: Moore and Meiselbaugh (1975) have suggested that such drugs suppress not only the adrenal function, but that of other endocrine glands as well. The presence of adrenal insufficiency has not, however, been hitherto supported by clinical or laboratory findings. Also in the present patient the authors failed to detect such a disorder. Whatever the mechanism of antimitotic drug-induced melanonychia may be, such aspect may rightly be included among the numerous patterns of cell dysplasias, due to chemotherapeutic drugs.
References Baserga, A.: Primi lineamenti di patologia arigenerativa. Min. med. 37, 247 (1956) De Nicola, P., Morsiani, M., Zavagli, G.: Nail diseases in internal medicine. 1st edn., p. 54. Springfield: Charles C. Thomas 1974 Harrison, B. M., Wood, C. B. S.: Cyclophosphamide and pigmentation. Brit. med. J. 1972 II, 352 Higuchi, K.: Chemotherapy of skin cancer with bleomycin. 6. intern. Congress of Chemotherapy, Tokyo, August 10-15, 1969 Ichikawa, T.: Discovery of clinical effects of bleomycin against squamous cell carcinoma and further development of its research. 10. intern. Cancer Congress, Houston, May 22-29, 1970 Moore, G., Meiselbaugh, D.: Hyperpigmentation after cancer chemotherapy. Lancet 1975 II, 128 Priestman, T. J., James, K. W.: Adriamycin and longitudinal pigmented banding of fingernails. Lancet 1975 I, 1337 Rothberg, H.: Adriamycin toxicity: unusual melanotic reaction. Cancer Chemother. Abstr. 58, 749 (1974) Scapoli, G. L., Bertocco, S., Spanedda, R., Bariani, L.: Iperpigmentazione da busulfano in corso di trattamento di leucemia mieloide cronica. Riforma med. 89, 149 (1975) Shah, P. C., Rao, K. R. P., Patel, A.R.: Cyclophosphamide-induced nail pigmentation. Lancet 1975 II, 548 Received December 18, 1976
