Keratosis Lichenoides Chronica (Nekam disease, lichen ruber moniliformis, lichen ruber acuminatus, lichen ruber planus, porokeratosis striata lichenoides, lichen verucosus et reticularis, lichenoid tri-keratosis)

Are You Confident of the Diagnosis?

What you should be alert for in the history

Along with the characteristic clinical findings, the longstanding and progressive clinical course of the disease is a highly characteristic feature.

Characteristic findings on physical examination

Keratosis lichenoides chronica is characterized by erythematous, or purple-colored hyperkeratotic lichenoid papules, linear and reticulate shapes by way of confluence of these papules, and verrucous hyperkeratotic plaques formed by coalescence of these papules. The lesions tend to have a symmetrical and more prominent distribution over the extensor surfaces of the extremities. Truncal and gluteal regions are frequently involved.

One-third of the cases are accompanied by palmoplantar hyperkeratosis, similar to dystrophic nail changes. Verrucous hypertrophy of the periungual tissue is a highly characteristic finding for the disease (Figure 1, Figure 2, Figure 3, Figure 4, Figure 5).

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Seborrheic dermatitis or rosacea-like lesions are seen in the face, along with psoriasiform plaques in 75% of the cases. The disease is seen as ulcers or infiltrating papules in the mucosal regions.

Blepharitis, keratoconjunctivitis, or iridocyclitis are the reported ocular findings. The eruption is generally asymptomatic, but in a few patients has been associated with severe pruritus.

The disease is chronic and progressive, while cases defining regression in summer months have also been reported. Spontaneous healing has also been defined. Clinical regression may be seen as patients get older.

Expected results of diagnostic studies

Histopathologically, epidermal hyperkeratosis, atrophy, focal parakeratosis (mostly found in follicular spaces), and wedge-shaped hypergranulosis (sometimes in zones of acanthosis) are characteristic findings of the disease (Figure 6). A dense band-like mononuclear cell infiltration in the mid- and upper dermis is observed in 87% of cases. Noserologic tests, genetic tests, and imaging studies are necessary for keratosis lichenoides chronica.

Figure 6.

Diagnosis confirmation

For the differential diagnosis of the disease, lichen planus (flat-topped purple papules), lichen planopilaris (scarring alopecia with follicular dropout and ertyhematous papules around individual hair shafts), pityriasis rubra pilaris (nutmeg grater papules, carnuba wax-like palms and soles, erythroderma), mycosis fungoides (atrophic patches in double-covered areas), and drug eruption (macular papular drug eruptions) should be taken into consideration.

Histopathological and clinical findings distinguish keratosis lichenoides chronica from these diseases.

The most challenging differential diagnosis is lichen planus. Some authors consider keratosis lichenoides chronica a variant of lichen planus. Typical reticular pattern spread of the lesions, dorsally uniting papules and plaques, face involvement, typical oral lesions, absence of the Wickham striae, long-term evolution, and ineffectiveness of systemic steroids are important clues to distinguish between keratosis lichenoides chronica and lichen planus. In addition, infiltration is denser and follicular involvement is more commonly seen in keratosis lichenoides chronica, when compared to lichen planus.

Who is at Risk for Developing this Disease?

Keratosis lichenoides chronica is a rare disease that affects adults aged 20-50 years. The mean age of the patients is 28 years.

There are no known differences in prevalence by sex or race. .

What is the Cause of the Disease?

Etiology

The exact cause of keratosis lichenoides chronica is not known.

Pathophysiology

The etiopathogenesis is unknown. No inheritance, influence of any other genetic alteration, or relation to any drug or any infection has been defined. No familial cases have been described. Some authors consider keratosis lichenoides chronica a variant of lichen planus.

Systemic Implications and Complications

Systemic complaints are generally absent, as is any relationship to other diseases, although a few cases have been reported in association with a variety of systemic disorders, including hypothyrodism, lymphoma, viral hepatitis (HCV), and glomerulonephritis.

Treatment Options

MEDICAL OPTIONS

Topical

Potent corticosteroids, salicylic acid, anthralin, calcipotriol, or tacalcitol

Systemic

Oral retinoids (e.g. acitretin, isotretinoin), antimalarial drugs, gold, methotrexate, dapsone, erythromycin, cyclosporine

PHYSICAL MODALITIES

Natural sunlight, photo(chemo)therapy, radiotherapy, photodynamic therapy with methyl 5-aminolaevulinic acid

Optimal Therapeutic Approach for this Disease

The problem with keratosis lichenoides chronica is generally the treatment, not the diagnosis. In the literature, many treatment modalities, including topical/systemic corticosteroids, salicylic acid, anthralin, antimalarial drugs, gold, methotrexate, dapsone, erythromycin, radiotherapy, and cyclosporine have been used; however, none of these agents have proven effective.

Mild cases can be treated with topical medications. Topical steroids (beginning with a low-potency hydrocortisone 2.5% cream or ointment and increasing to triamcinalone 0.1% cream or ointment) are usually tried first, but this treatment usually has no beneficial effect on the progression of the lesions.

Case reports have shown that topical calcipotriol or tacalcitol induced marked clinical improvement. The exact molecular mechanism by which vitamin D3 analogues are able to exert their effects on keratosis lichenoides chronica is unknown. The most commonly proposed mechanisms have been suppression of lymphocyte proliferation, induction of terminal differentiation, and inhibition of proliferation of keratinocytes. Topical calcineurin inhibitors may have a role in the treatment of keratosis lichenoides chronica, although they have not been used for this indication.

More severe cases, especially those with widespread involvement, may need intensive therapy. Keratosis lichenoides chronica appears to improve with both natural sunlight and photochemotherapy. Keratosis lichenoides chronica treatment with psoralens and ultraviolet A (PUVA) resulted in partial to excellent results. One case was still in remission after 2 years.

PUVA has anti-inflammatory, antiproliferative, and immunosuppressive effects, and lymphocytes appear to be more susceptible to its effects as compared to keratinocytes; however, it is not known which of these effects contribute to the therapeutic efficacy of PUVA in keratosis lichenoides chronica. Risks and benefits of this treatment should be considered, especially in long-term treatment of young patients. Broadband ultraviolet B (UVB) or narrowband UVB can be attempted; however, there are no data to support their use.

Oral retinoids (e.g. acitretin, isotretinoin), given in doses up to 0.5mg/kg/day, have been the most effective treatment for keratosis lichenoides chronica. Although acitretin has keratolytic and anti-inflammatory activities, and decreases the inflammation in the dermis and modulates terminal differentiation of epidermal cells, its role in keratosis lichenoides chronica has not been understood so far. The major advantage of acitretin is the rapid onset of its action.

Flattening of the lesions has been reported within the first month of the therapy, while complete clearance has been achieved after 4-6 months. In some cases, the improvement was maintained during 8-9 months of follow-up; however, prolonged use of acitretin is limited by its adverse effects. Therapy is typically lifelong if the patient gets an adequate therapeutic response. The use of drug holidays may help decrease the chance of side effects.

Because photochemotherapy, acitretin, and calcipotriol have been proven to be effective when used as monotherapy in order to achieve a better and rapid therapeutic effect, PUVA (2-3 times per week), in combination with acitretin (25mg/day) and calcipotriol ointment daily, was used successfully in keratosis lichenoides chronica. Combining calcipotriol, acitretin, and PUVA may be a worthwhile therapeutic option in this difficult-to-treat disease. This combination may also help limiting the potential toxicity of these drugs.

Patient Management

Although the disease has a progressive course, patients should be told that the disease is limited to the skin.

Patients should be told about the long-lasting nature of keratosis lichenoides chronica. Because keratosis lichenoides chronica is a rare disease, no large randomized controlled clinical trials have been conducted for therapy; all data were gathered from case reports. Therefore, several treatments may need to be tried.

Patients should be told about the potential adverse effects from the various treatments offered.

On diagnosis, a thyroid-stimulating hormone (TSH) and HCV test should be performed to look for possible associations with thyroid disease or hepatitis C.

Unusual Clinical Scenarios to Consider in Patient Management

A few cases of keratosis lichenoides chronica have been reported in association with a variety of systemic disorders, including hypothyrodism, lymphoma, and viral hepatitis. Although most cases are unassociated with any systemic problem, because of the rarity of the condition, an inquiry should be made about the possibility of these disorders, with the appropriate work-up for them, should there be any suspicion of their existence.

What is the Evidence?

Boer, A. “Keratosis lichenoides chronica: proposal of a concept”. Am J Dermatopathol. vol. 28. 2006. pp. 260-75. (This article presents an excellent review of the history of the disease, and also details the clinical and histopathological features and the differential diagnosis of keratosis lichenoides chronica . The article also provides an analysis of the cases that were reported to date and provides clues that can be used in confirming the diagnosis.)

Demirci, E, Boyvat, A, Arica, IE. “Keratosis lichenoides chronica: marked response to PUVA in combination with acitretin”. Acta Dermato Venereol. vol. 85. 2005. pp. 552-3. (Demirci reports a 52-year-old male patient with recalcitrant keratosis lichenoides chronica. This patient had failed to respond to acitretin and PUVA when used as a monotherapy, but the combination of these treatments provided marked treatment response after 2 months of the treatment.)

Wozniacka, A, Schwartz, RA, Omulecki, A, Lesiak, A, Sysa-Jedrzejowska, A. “Keratosis lichenoides chronica: a diagnostic and therapeutic challenge”. Clin Exp Dermatol. vol. 31. 2006. pp. 48-50. (This case report presents a 45-year-old man with recalcitrant keratosis lichenoides chronica. The patient’s disease was unresponsive to topical treatment with tar, retinoic acid, and local steroids, and also to systemic steroids, antimalarials, and methotrexate.)

Avermaete, A, Kreuter, JA, Stacker, M. “Keratosis lichenoides chronica: characteristics and response to acitretin”. Br J Dermatol. vol. 144. 2001. pp. 4122-4. (Avermaete and coworkers present a 31-year-old male with keratosis lichenoides chronica that was resistant to systemic and topical corticosteroids in combination with PUVA phototherapy; however, all skin lesions had completely resolved after 6 months of treatment with acitretin.)

Ghislain, PD, De Beir, A, Creusy, C, Modiano, P. “Keratosis lichenoides chronica: report of a new case, with success of PUVA therapy”. Dermatol Online J. vol. 7. 2001. pp. 4(This article reports the case of a 78-year-old woman with typical clinical and histological findings. This case illustrates an excellent response of the disease to PUVA.)

Nijsten, T, Mentens, G, Lambert, J. “Vascular variant of keratosis lichenoides chronica associated with hypothyroidism and response to tacalcitol and acitretin”. Acta Derm Venereol. vol. 82. 2002. pp. 128-30. (This case confirms the existence of a vascular variant of keratosis lichenoides chronica. The article discusses the therapeutic modalities and reports the effectiveness of acitretin, in combination with tacalcitol, in keratosis lichenoides chronica.)

Grunwald, MH, Hallel-Halevy, D, Amichai, B. “Keratosis lichenoides chronica: response to topical calcipotriol”. J Am Acad Dermatol. vol. 37. 1997. pp. 263-4. (Grunwald reports a 53-year-old man with keratosis lichenoides chronica that was treated successfully with topical calcipotriol. This case shows a good example of calcipotriol-induced marked clinical improvement in keratosis lichenoides chronica.)

Douri, T, Shawaf, AZ. “Keratosis lichenoides chronica: report of a new case with partial response to PUVA therapy”. Dermatol Online J. vol. 11. 2005. pp. 28(This article presents a case of a 35-year-old Syrian woman who presented with a history of keratotic plaques and papules of the limbs for several years, as well as a seborrheic dermatitis-like facial eruption. The diagnosis was based on clinical and histological findings. Treatment with isotretinoin was without benefit and the patient had partial response to PUVA after twenty-six sessions [86.5 Joules].)

Kunte, C, Kerschenlohr, K, Röcken, M, Schirren, C. “Keratosis lichenoides chronica: treatment with bath-PUVA”. Acta Derm Venereol. vol. 87. 2007. pp. 182-3. (This case report describes two young adults with typical clinical features of keratosis lichenoides chronica, and provides bath-psoralen plus ultraviolet light A therapy as a potentially useful treatment for this rare disease, which is resistant to most classical anti-inflammatory therapies.)

Lopez-Navarro, N, Alcaraz, I, Bosch, RJ, Tejera, A, Herrera, E. “Keratosis lichenoides chronica: response to photodynamic therapy”. J Dermatolog Treat. vol. 19. 2008. pp. 124-5. (Lopez Navarro reports the first case of keratosis lichenoides chronica in which there was a marked response in localized areas to photodynamic therapy with methyl 5-aminolaevulinic acid.)

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