Ankica Smeh-Skrbin

Gordana Krnjević-Pezić

Ivan Dobrić

Pero Vržogić

English

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15Naphthalene in the Treatment of Patients with Atopic Dermatitis   Ankica Smeh-Skrbin1, Ivan Dobrić2, Gordana Krnjević-Pezić1, Pero Vržogić11Naftalan Special Hospital for Medical Rehabilitation, Ivanić Grad; 2University Department of Dermatology and Venereology, Zagreb University Hospital Center, Zagreb, CroatiaSUMMARY Atopic dermatitis is a chronic relapsing inflammatory skin disease the incidence of which has been constantly growing in all age groups. Research into the use of naphthalene in the treatment of patients with psoriasis proved its anti-inflammatory and antiproliferative effects as well as a satisfactory remission for months in more than 70% of treated patients with psoriasis. The present study was undertaken to investigate the efficacy of naphthalene in the treatment of patients with atopic dermatitis. According to study results, naphthalene therapy proved efficacious and free from side effects in 20 atopic dermatitis patients.KEY WORDS: naphthalene preparation, naphtha oil, hydrocarbon complex, sterans, polyaromatics, naphthalene therapyINTRODUCTION Naphthalene therapy for atopic dermatitis (AD) was assessed at Naftalan Special Hospital for Medical Rehabilitation in Ivanić Grad. Naphthalene is natural earth mineral oil, a dense, dark-brown liquid with a high specific weight (0.93-0.98 at 15 °C). As heavy oil, it is found in surface earth layers (100-700 m) (1-5). Naphthalene consists of a small quantity of light fractions (petrol, ligroin, kerosene) and paraffin, and a high percentage of polycyclic naphthol hydrocarbons  (cyclopentanoperhydro-phenantrene) structures. Sterans are most sig-nificant as carriers of the naphthalene medicinal properties. Sterans have a chemical structure sim-ilar to hormones and vitamins. The size of its mol-ecule is 200-450 Da, which makes possible for the molecule to pass through the healthy (500 Da) and diseased (700 Da) skin (2,5-8). Naphthalene as a natural medicinal product with proven efficacy and antiproliferative properties in psoriasis (3,4-8), and as an antiangiogenic factor in psoriatic lesions (9). A new naphthalene preparation, naphthalene AA-final (Ivalan), enriched with sterans, constituents believed to represent active naphthalene com-ponents, while the content of polyaromatics has been substantially reduced, is currently available at Naftalan Special Hospital for the management Acta Dermatovenerol Croat     2007;15(1):15-19     SHORT SCIENTIFIC COMMUNICATIONCorresponding author: Ankica Smeh-Skrbin, MDNaftalan Special Hospital for Medical RehabilitationOmladinska 23aHR-10310 Ivanić Grad CroatiaReceived: December 13, 2006.Accepted: February 20, 2007.16 ACTA DERMATOVENEROLOGICA CROATICAof psoriasis (10). Naphthalene therapy as one of newest topical AD treatments was assessed in the present study. MATERIAL AND METHODS The study included 20 AD patients (9 male and 11 female), aged 15-65, most of them in the 15-25 age group. Study patients presented various clinical pictures of AD. Clinical evaluation accord-ing to SCORAD index (11) and photographing were done before and after therapy. Biochemistry laboratory testing including complete blood count (CBC), erythrocyte sedimentation rate (ESR), blood glucose (BG), aminotransferases, alkaline phosphatase (AP), albumin, bilirubin, creatinine, cholesterol, triglycerides (TG), blood urea nitro-gen (BUN) and serum electrolytes, urinalysis and histologic evaluation were performed before and after 3 weeks of therapy. Total serum IgE levels were quantitatively determined using the CAP system techniques. Naphthalene therapy was administered ac-cording to the usual protocol, applied for some 15 years in the treatment of patients with psoriasis and rheumatic diseases at Naftalan Special Hospital for Medical Rehabilitation in Ivanić Grad, Croatia. Naphthalene therapy was applied once daily with warm baths for 12-14 minutes in tubs with naphtha-lene oil, at a temperature of 34-38 °C, for 3 weeks. After bath, neutral creams (Eucerin intensive cream or Belobaza cream and Eucerin cream shower oil) were applied. An oral antihistaminic (diphenhydr-amine, Dimidril, 3x1 tbl) was used occasionally.  RESULTSClinical evaluation after 3 weeks of naphthalene therapy revealed improvement of clinical assess-ment in all cases (Figs. 1-6), along with a reduc-tion of itching and sleeping disturbance. The mean SCORAD index was 75.4 before and 30.9 after naphthalene therapy. Graphic records of SCO-RAD index are shown in Fig. 7.Figure 4. Atopic dermatitis in patient K. O. after 3-week naphthalene therapy.Figure 1. Atopic dermatitis in patient R. M. before naphthalene therapy.Figure 2. Atopic dermatitis in patient R. M. after 3-week naphthalene therapy.Figure 3. Atopic dermatitis in patient K. O. before naphthalene therapy.Smeh-Skrbin et al.     Acta Dermatovenerol CroatNaphthalene in the treatment of atopic dermatitis      2007;15(1):15-19 17ACTA DERMATOVENEROLOGICA CROATICA Histological evaluation Probatory excisions were done in all 20 patients before and after 3-week naphthalene therapy. In 11 patients, AD could not be identified on control histology findings, whereas in nine patients control histology findings showed acanthosis (epidermis widening) to be the same or reduced.  Subepider-mal perivascular infiltrate of lymphocytes and fibro-histiocytes was reduced or highly reduced (Figs. 8a, 9a). Reduction of inflammatory infiltration was observed in all 20 patients (Figs. 8b-10b). Figure 5. Atopic dermatitis in patient S. M. before naphthalene therapy.Figure 6. Atopic dermatitis in patient S. M. after 3-week naphthalene therapy.Figure 7. Graphic record of SCORAD index in 20 atopic dermatitis patients before and after naph-thalene therapy.Figure 8. (a) Patient R. M. before naphthalene therapy: parakeratosis, acanthosis and inflamma-tory infiltration in the subepidermal dermis (HE; X220); (b) patient R. M. after 3-week naphthalene therapy: acanthosis and reduction of the inflam-matory infiltration (HE; X220).IgE evaluationTotal IgE level was higher after than before naph-thalene therapy in only four, unchanged in six and reduced in ten of 20 AD patients (Table 1).Biochemistry laboratory parameters In all 20 patients, the values of CBC, ESR, BG, aminotransferases, AP, albumin, bilirubin, cre-atinine, BUN, serum electrolytes, calcium, cho-lesterol, TG and urinalysis determined before and after 3-week naphthalene therapy were within the normal range. The naphthalene min-eral earth oil caused no hematotoxicity, hepa-totoxicity or nephrotoxicity in AD patients. DISCUSSION In all 20 patients, clinical improvement in terms of reduction or disappearance of pruritus and sleep disturbance, reduction of skin lesions and reduc-tion of SCORAD index (changes in total intensity, Smeh-Skrbin et al.     Acta Dermatovenerol CroatNaphthalene in the treatment of atopic dermatitis      2007;15(1):15-19 18 ACTA DERMATOVENEROLOGICA CROATICAPatient No.                             Total IgEBefore naphthalene therapyAfter naphthalene therapy1 37 k IU/L  (122) 70 k IU/Ll (122)2 1117 IU/mL (120) 552.6 IU/mL (120) 3 144 IU/mL 130 IU/mL4  85 IU/mL 85 IU/mL 5  88 k IU/L    88 k IU/L6  822 IU/mL 719 IU/mL7 1329.2 k IU/L 1220 k IU/L8  81 k IU/Ll 81 k IU/L9 159 IU/mL 140 IU/mL10 130 IU/mL 130 IU/mL 11 144.1 IU/mL 144.1 IU/mL12  619 IU/mL 2000 k IU/L 13  210.3 IU/mL 234.6 IU/mL 14  27.1 IU/mL  27.1 IU/mL15 3275 IU/mL 2877 IU/mL16 2240.60 k IU/L 2175.40 k IU/L17 2409.0 k IU/L 2009.0 k IU/L18 3898 k IU/L 4000 k IU/L19 4000 k IU/L 2400 k IU/L20 1888.0 k IU/L 1105.0 k IU/LTable 1. Total IgE results before and after naph-thalene therapy in 20 atopic dermatitis patients            Figure 9. (a) Patient K. O. before naphthalene therapy: acanthosis and inflammatory infiltration in the upper part of the dermis (HE; X220); (b) patient K. O. after naphthalene therapy: acanthosis and reduction of the inflammatory infiltration (HE; X220).i.e. erythema, edema, excoriation, lichenification and crusts) was recorded (11). Tolerability was good and free from side effects or alterations in hematology and biochemistry parameters. In our 20 patients, remission lasted for a mean of 20.4 months. Naphthalene proved to be a good thera-peutic option in AD patients with a 70% efficacy. Considering that naphthalene is a non-steroidal therapy, we can recommend it in the treatment Figure 10. (a) patient S. M. before naphthalene therapy: subepidermal inflammatory infiltration (HE; X180); (b) patient S. M. after naphthalene therapy: reduction of the inflammatory infiltration (HE; X220).of AD in both adults and children. Naphthalene therapy is one of therapeutic options for AD and is harmless for health in general. No unwanted ef-fects that would require discontinuation of naph-thalene therapy were recorded. Naphthalene therapy offers a new therapeutic approach in the management of AD.Smeh-Skrbin et al.     Acta Dermatovenerol CroatNaphthalene in the treatment of atopic dermatitis      2007;15(1):15-19 19ACTA DERMATOVENEROLOGICA CROATICAReferences1.   Krnjević-Pezić G, Vržogić P, Ostrogović Ž, Smeh-Skrbin A, Dobrić I. Some hematological and biochemical parameters in psoriatic pa-tients treated with naphthalan. Acta Dermato-venerol Croat 1997;5:49-53.2.   Alajbeg I, Krnjević-Pezić G, Alajbeg I, Smeh-Skrbin A, Vržogić P. Comparison of the compo-sition of some petroleum samples which may be applied for skin and mucous membrane treatment. J Pharm Biomed Anal 2000;22:75-84. 3.   Thaci D, Schindewolf M, Smeh-Skrbin A, Krnjević-Pezić G, Vržogić P, Dobrić I, et al. Heavy naphthene oil exhibits antipsoriatic effi-cacy in vivo and antiproliferative as well as dif-ferentiation-including effects on keratinocytes in vitro. Arch Dermatol 2000;136:678-9.4.   Dobrić I, Smeh-Skrbin A, Krnjević-Pezić G, Vržogić P. Evaluation of the efficacy of naphthene-based oil (naphthalan), a natu-ral earth oil in the treatment of patients with psoriasis vulgaris; does naphthalan provide an appropriate “pharmacologic pause” in local therapy for psoriasis. Acta Dermatovenerol Croat 2001;9:197-205.5.   Alajbeg I, Krnjević-Pezić G, Smeh-Skrbin A, Vržogić P, Vučićević-Boras V, Dobrić I, et al. Non-aromatic naphthalene preparation: preliminary clinical study in the treatment of psoriasis vulgaris. J Pharm Biomed Anal 2001;26:801-9.6.   Vržogić P, Jakić-Razumović J, Pašić A. Effect of naphthalan on epidermal proliferation activi-ty and CD3, CD4 and CD8 lymphocyte count. Acta Dermatovenerol Croat 2003;11:65-9.7.   Vržogić P, Ostrogović Ž, Alajbeg A. Napht-halan – a natural medicinal product. Acta Dermatovenerol Croat 2003;11:178-4.8.   Vržogić P. International Symposium Current State on Psoriasis and Naphthalene Therapy, Ivanić Grad, September 19, 2003. Acta Der-matovenerol Croat 2003;11:270-1.9.   Vržogić P, Jakić-Razumović J, Lipozenčić J. Naphthalanotherapy reduces angiogenic factor in psoriatic lesions. Acta Dermatovene-rol Croat 2004;12:7-11.10. Lipozenčić J. A new naphthalene preparation in the management of psoriasis. Acta Dermat-evenerol Croat 2005;13:189.11. The European Task Force on Atopic Dermatitis. Severity scoring of atopic dermatitis: the SCO-RAD index. Dermatology 1993;186:23-31.Radeiner, mineral water; year 1937.(from the collection of Mr. Zlatko Puntijar)Smeh-Skrbin et al.     Acta Dermatovenerol CroatNaphthalene in the treatment of atopic dermatitis      2007;15(1):15-19 

Naphthalene in the Treatment of Patients with Atopic Dermatitis

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