Non-malignant skin changes in transplant patients

Annelies Avermaete, Peter Altmeyer and Martina Bacharach-Buhles

Department of Dermatology, Ruhr-University Bochum, Bochum, Germany

Keywords: infectious diseases; lichen ruber planus; non-malignant; porokeratosis; transplant

Introduction

The skin pathology seen in graft recipients is unique because they are usually seen in patients who have a long history of renal disease, where the characteristic lesions seen in pre-terminal failure followed by dialysis-induced skin pathology had developed. The skin changes after renal transplantation partially replace, and partially are superimposed upon, the skin lesions characteristic for these preceding periods.

Skin changes after kidney transplantation

Successful renal transplantation causes a sudden alteration of skin function and subcutaneous pathology. Pre-existing skin pathology changes and a pattern of skin pathology, partly benign, partly malignant, appears. While immunosuppressive drugs cause skin pathology in patients exposed to the same immunosuppressive drugs as the renal graft recipient, the skin pathology after renal transplantation is unique because of the major pre-existing skin pathology. Our clinical experience would suggest an increased sensitivity of the skin.

Influence on pre-existing skin changes

Decreased sebaceous and sweat gland production normalizes slowly after transplantation [1] and at the same time, the xerodermia which is characteristic of terminal renal failure improves. Ichthyosis is seen in no more than 8% of transplanted patients. In a few cases the increase in sebaceous gland production even leads to seborrhoea. Pruritis tends to disappear: only 2% of transplanted patients complain of pruritus, compared with 50–75% of dialysis patients. The skin also becomes less vulnerable. Skin vulnerability is increased in almost all dialysis patients, but this is seen only in 16% of renal graft recipients [2,3].

Similarly Raynaud's syndrome tends to disappear. The Raynaud phenomenon can be provoked in no more than 2% of graft recipients, whilst 51% of patients on dialysis complain of Raynaud's syndrome [4]. Even histological lesions of the vessels disappear. In the dialysis patient, complement and immune globulin deposits are seen in skin vessels, which disappear after successful renal transplantation [5,6]. In cross-sectional studies, Carpal tunnel syndrome is seen in 2% of transplanted patients, compared with 32% of dialysed patients [2], but this may be due to selection bias and true reversibility has not been.

Unfortunately, premature ageing of the skin, i.e. actinic elastosis, is not influenced by renal transplantation. This type of skin pathology, which presents as increased wrinkling and is histologically characterized by deposition of elastotic material, is apparently irreversible.

Dermatoses appearing after transplantation

New dermatoses can appear after transplantation, e.g. lichen ruber planus, urticarial and vesicular exanthemas, facial oedema, or rarely purpura. One of the causes is graft vs host disease, brought about by donor-specific lymphocytes in the graft. Further pathology, partly induced by the immunosuppressive agents, includes hypertrichosis, gingival hyperplasia, seborrhoeic eczema, perioral dermatitis, and porokeratoses [7].

Lichen ruber planus

Lichen ruber planus is a non-infectious inflammatory dermatosis, which may involve skin as well as mucous membranes. It is characterized by flat-topped, violaceous, shiny pruritic papules of the skin (Figure 1Go) and milky white papules in the mouth. Similar to psoriatic lesions, lichen ruber planus can be provoked by physical and chemical triggers. This is called Koebner's phenomenon. This explains why the typical lichen ruber planus papules may be seen in excoriated skin. The papules have preferential locations and follow typical pattern of distribution: flexor aspects of the wrists, lumbar region, mucosal membranes, and nails. Nail involvement may lead to destruction of the nail fold and nail bed with a tendency to onychoschisis. Destruction of the hair follicles can lead to scarring alopecia.



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Fig. 1.  Lichen ruber planus: violaceous, shiny pruritic papules on the foot.

 
In the background population, lichen ruber planus usually appears between the third to sixth decade; it may appear at any age in renal transplant recipients.

Seborrhoeic and perioral dermatitis

Seborrhoeic dermatitis is common in the graft recipient. It is characterized by circumscribed red and scaling skin in regions characterized by a high density of active sebaceous glands: midfacial region, scalp, and presternal region. It has been suggested that the fungus Pityrosporon ovale plays a role in its pathogenesis.

Perioral dermatitis is characterized by discrete erythematous micropapules that often become confluent, forming inflammatory plaques, especially in the perioral and periorbital skin.

Predisposing conditions are a seborrhoeic skin type or gastrointestinal disorders. It is important to exclude contact allergy to cosmetic preparations and to fluorinated toothpaste. The disease may be markedly aggravated by topical corticosteroids. It has been suggested that infection by Candida albicans or bacterial microbes play an aetiological role and this may explain why perioral dermatitis is frequent after transplantation.

Porokeratosis

Porokeratosis is a disorder characterized by abnormal differentiation of the epidermis. The hallmark is the hyperkeratotic skin lesion with the tendency to centrifugal growth. Usually one or more rapidly growing skin lesions are seen which present initially as a hyperkeratotic papule, which later exhibits the typical centrifugal growth pattern (Figure 2Go). The characteristic histological lesion is a focal porokeratosis, the so-called cornoid lamella. Within this area the cell nuclei persist up to the horny layer, representing an immature keratinization.



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Fig. 2.  Porokeratosis: hyperkeratotic skin lesions, centrifugal growth.

 

Graft vs host disease

Graft vs host disease is an immunological reaction caused by a local interaction between donor lymphocytes and host target cells. The characteristic acute cutaneous changes range from maculopapular eruptions to toxic epidermal necrolysis. Chronic changes comprise lichenoid eruptions and sclerodermatous changes. More rarely, keratoconjunctivitis or mucosal involvement with oesophageal and vaginal strictures, gastrointestinal pathology, liver involvement, or pulmonary insufficiency are seen.

Infectious diseases

Apart from cardiovascular complications, infections are the most frequent complication and cause of death in the graft recipient. The immunosuppressed state caused by immunosuppressive drugs, promotes viral and bacterial infections and predosposes to several types of malignancies.

The most commom viral infections of the skin are herpes simplex, Verrucae vulgares (Figure 3Go) and Condylomata acuminata.



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Fig. 3.  Verrucae vulgares: Verrucous tumours on the fingers.

 
Herpes simplex virus infection is characterized by grouped vesicles arising on an erythematous base on keratinized skin or mucous membranes. The most frequent presentation is herpes simplex labialis (cold sore). Immunosuppressed patients may experience cutaneous or occasionally systemic dissemination of the disease with involvement of the central nervous system or inner organs. The herpes simplex virus is a DNA virus of which two types can be differentiated: lesions of herpes simplex type I occur on the oral mucosa and lips, rarely on the face or trunk, whilst the lesions of herpes simplex type II are seen in the genital or genitogluteal region.

Verrucae vulgares and C. acuminata are caused by HPV viruses. Verrucae vulgares are typically the result of infection with human papilloma virus types 1, 2, 4, and 7 (Figure 3Go), Verrucae plantares by HPV 1, 2, and 4, C. acuminata by HPV 6 and 11 and rarely by HPV 16 and 18. Long-standing infection with HPV types 16 and 18 can lead to the development of carcinoma, particularly cervical carcinoma.

Verrucae vulgares typically develop in predilection sites such as hands, fingers, and occasionally face. Warts can be treated using operative curettage, laser surgery or a local immunostimulating drug, imiquimod, which constitutes effective treatment.

Apart from viral infections of the skin, bacterial, and fungal infections of the skin can also develop during immunosuppressive treatment.

Pyoderma, or superficial infection of the skin with staphylococci or streptococci is virtually never seen in healthy adults, whilst in children, impetigo contagiosa is not infrequent. In immunosuppressed graft recipients such bacterial skin infections are seen even in adults (Figure 4Go). Impetigo is characterized by small or large vesicles or bullae on an erythematous basis. The lesion spreads rapidly. After rupture the lesions present as shallow erosions and yellow crusts. Streptococcal infection causes small vesicular lesions. In contrast, staphylococcal infection causes larger bulluos eruptions. These infections have a predilection for the skin around the mouth and nose, but scattered lesions can also occur in other locations. Apart from topical treatment, systemic antibiotic therapy is necessary.



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Fig. 4.  Pyoderma of the face: superficial infection with staphylococci.

 
The most common fungal infection is tinea pedis. Even before transplantation many patients suffer from dermatophytic infections of the feet. Usually the interdigital area is involved, presenting with itchy, painful fissures and well-demarcated erythema with minute papules at the margin as well as fine white scaling of the sole. This morphology is indicative of fungal infection. Nail involvement leads to yellow, brown discoloration of the nail plate. The nail becomes opaque, thickened, friable, and finally is lifted by the underlying hyperkeratotic debris in the nail bed (Figure 5Go). Immunosuppressive treatment causes massive deterioration of pre-existing fungal infection (Figure 6Go). Tinea pedis responds well to topical treatment. In contrast, treatment of tinea unguium, i.e. fungal infection of the nail, is often frustrating. Such treatment has to be administered for between 6 and 9 months.



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Fig. 5.  Tinea unguium: yellow, brown discoloration of the nail plate.

 


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Fig. 6.  Tinea barbae: deep dermatophytic infection.

 

Conclusion

In summary, on the one hand, in the recipient of a renal allograft, recruitment of uraemia-specific pre-existing skin problems is seen. This benefit is traded off against the development of alternative skin lesions, caused by immunosuppression. These lesions include bacterial or viral infections on the one hand and malignancy on the other hand.

Notes

Correspondence and offprint requests to: M. Bacharach-Buhles, Evangelisches Krankenhaus, Bredensheider Strasse 54, D-45525 Hattingen, Germany. Email: martina.bacharach\|[hyphen]\|buhles{at}ruhr\|[hyphen]\|uni\|[hyphen]\|bochum.de Back

References

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  3. Morton CA, Lafferty M, Hau C, Henderson I, Jones M, Lowe JG. Pruritus and skin hydration during dialysis. Nephrol Dial Transplant1996; 11: 2031–2036[Abstract]
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