Hyalinosis cutis et mucosae: a 30 year follow up of a female patient

ARTICLE

Auteur(s) :, Ines BRAJAC^*, Marija KAŠTELAN, Franjo GRUBER, Zdravko PERIŠ

Department of Dermatology, University Hospital Centre Rijeka, Krešimirova 42, 51000 Rijeka, Croatia
^*Ines Brajac, Fax (+385) 51 658 281. E-mail: ines.brajac@medri.hr

accepté le 7 Juin 2004

Case report

On admission, the extensive skin lesions were present on the face and body. The yellowish-white papules, vesicles and crusted plaques associated with atrophic areas and scars were noticed on the trunk (( Fig 1 )). On the elbows, knees, over the knuckles and sides of the hands verrucous plaques were present. The papules and plaques were also observed on the buccal mucosa, tonsils and pharynx. The tongue and lips were enlarged; the frenulum was thickened, thus restricting speech. Her face was hypomimic and coarse, with scars on the forehead, cheeks and sides of the head. Multiple small waxy yellow papules were found along the eyelids, and eyebrows (( Fig 2 )). Lesions on the scalp caused alopecia and the patient wore a wig. The scull X-rays revealed symmetric calcifications just lateral and superior to sela turcica. Her quality of life was seriously impaired by the disfiguring lesions and the permanent hoarseness. She was depressed, reserved, unsociable, aggressive and almost completely isolated from her peers.

The patient had almost identical lesions at the age of 12 years, when her parents had not yet decided to submit her to dermabrasion. However, the girl felt wretched because of her aged appearance and made her parents decide on the procedure.

After obtaining informed consent from her parents, face dermabrasion was performed. Complete remission of the abraded lesions was obtained after 10 days, and a full reversion of the histological finding occurred within 2 months. Regenerated, pink coloured skin had the clinical and histological appearance of normal skin. Verrucous and atrophic lesions have mostly disappeared and the skin was more elastic and movable.

A few months later, we abraded the lesions of the oral mucosa rather deeply. After abrasion of the inner surfaces of the lips, a completely normal mucous membrane was seen, both histological and macroscopically. Regenerated mucous membrane lost its hardness and regained normal elasticity.

In 1996, the patient came to our Department to the regular check up. Previous dermabrasions had markedly improved the skin on treated areas. However, prominent and disfiguring hyperkeratoses were observed on the palmar and dorsal sides of her hands, as well as on the elbows and knees. So, after an informed consent, the patient was treated with etretinate 1.0 mg/kg daily for two months and then with 0.75/mg/kg. After 4 months, the examination revealed a substantial improvement of the verrucous lesions on the knees, elbows and palms. The patient herself also confirmed that her skin looked better and became more elastic. However, as the plasma level of cholesterol, triglicerids and transaminases increased, the therapy was stopped. Unfortunately, after few months the lesions almost completely relapsed.

Last year, we saw our patient one more time. She was married, looking pretty good, had a healthy child, and was overall satisfied with her life. The changes on her face but also on the trunk where dermabrasion was not performed, were largely reversed. (( Fig 3 ) and ( Fig 4 )).

Discussion

The course of disease in our patient was protracted, with a slight tendency to slow down in adult life. This tendency for improvement is in accordance with some other reports [3], however, Hofer et al. reported a progression of oral lesions with increasing age [11].

The reason why not all but only certain patients with HCM develop spontaneous improvement is still unclear. The differences could exist between patients with early and late onset of the disease as well as between patients with different severity of the disease. So far, there is no clear association between the clinical phenotype and the course of HC. We observed not only a therapeutic but also a spontaneous improvement in our patient, suggesting that early onset of the disease could lead to a slight improvement after the age of 50. The natural course of the disease in our patient with a tendency to spontaneous improvement was observed on the trunk, where dermabrasion was not performed.

The decrease in severity in older age suggests that several pathogenetic mechanisms might be involved in spontaneous improvement such as the self-limited nature of the disease or changes in the regenerative properties of skin cells in older age. According to some authors, the disease is not likely to regress either spontaneously nor with therapy [11, 15].

Carbon dioxide laser surgery of thickened vocal cords proved to be effective for the treatment of hoarseness as reported by Haneke et al. [16]. The skin changes could be largely reversed by excising the hyaline material with no remission of lesions [17]. However, the use of surgical therapies is questionable because, according to some authors, trauma has seemed to increase deposition of hyaline in skin and mucous membranes [11].

Although the pathophysiology underlying these depositions is not clear, one explanation might be that lack of ECM 1a leads to defective protein binding. If ECM normally binds type IV collagen, the lack of this potentially regulatory protein-protein interaction in HCM could then result in increased type IV collagen expression and typical histopathological changes [4]. In human skin ECM 1a mRNA is expressed throughout the epidermis with the strongest expression in the basal and first suprabasal cell layers, whereas expression of ECM 1 b mRNA is predominantly found in spinous and granular cell layers. Within the epidermis, ECM has a role in the control of keratinocyte differentiation [18].

In our experience, the cutaneous lesions in HCM may be completely removed by dermabrasion without deposition of hyaline material, which is confirmed histologically and clinically during the long follow up of the patient. This suggests that no intervention was related to the development of new lesions as proposed.

Various genodermatoses can be improved by dermabrasion. Permanent success could be achieved in Darier’s disease and Morbus Hailey-Hailey [19, 20], but only a slight improvement in black ichthyosis or Mb. Pringle [21]. In our opinion, complete regression is achieved in those disorders in which all cells that express the intrinsic gene defect are removed by dermabrasion, and normal cells of the skin adnexa can regenerate the deficient skin layers. In M. Hailey-Hailey and M. Darier dermabrasion is effective, because deep cells of the appendages do not express the gene defect.

Complete clinical remission of abraded regions in our patient with HCM was immediately obtained, and a full reversion of the histologic finding occurred within two months. Dermabrasion allows for normal micro and macroreconstruction of the damaged layers to occur shortly after the procedure, which could never occur spontaneously in such a short time [17]. Namely, normal cells of the skin appendages can regenerate the deficient skin layers, as happened in our female patient with HCM.

The patient described here had also been treated with etretinate for four months, but the therapy was stopped because of the increasing levels of cholesterol, triglicerids and transaminases. A few months after retinoid therapy the lesions almost completely relapsed. Nevertheless, we clearly demonstrated that retinoids may act on the cutaneous lesion in HCM. The observation that the skin lesions respond to such a brief treatment period is encouraging, and perhaps with a longer course of therapy a better improvement with a longer period of remission could be seen.

There has been no promising treatment for HCM to date. Nevertheless, the lesions, especially on face and other uncovered areas of the body, should be removed or at least corrected as soon as possible to enable the child a normal psychophysical development. Fortunately, the face itself, because of the abundance of small follicles, sweat and sebaceous glands, is the best area for performing dermabrasion. The successful correction of the defect could improve the overall quality of a child’s life.

The dermabrasion has excellent results, long-lasting effects and no side effects. Not all of the lesions can be removed by single act of dermabrasion, so the procedure has to be repeated. We should avoid retinoid therapy in childhood because of side effects on bone development. In the adult life, with a longer course of retinoids, we can further improve skin appearance and life quality.

References

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4 Hamada , McLean , Ramsay , et-al. Lipoid proteinosis maps to 1q21 and is caused by mutations in the extracellular matrix protein 1 gene (ECM1) Hum Mol Genet 11 2002 833-840

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