Lichen Nitidus

Etiology

Lichen nitidus is a rare inflammatory dermatosis with an incompletely understood etiology. Genetic predisposition has been proposed because familial cases have been reported in the literature.[3] Although the close clinical association between lichen nitidus and lichen planus has led to speculation that they may represent related disorders, results from immunohistochemical studies supported lichen nitidus as a distinct entity rather than a variant of lichen planus.[1] Lichen nitidus has also been reported in association with systemic conditions, including Crohn disease, Niemann-Pick disease, amenorrhea, Down syndrome, advanced HIV infection, and after tattoo placement.[3][4][5] Rare cases have additionally been described after interferon-alfa and ribavirin therapy for hepatitis C.[1][5] Generalized purpuric lichen nitidus is an exceptionally uncommon variant and has been reported following nivolumab therapy, suggesting a possible immune-mediated mechanism related to immune checkpoint inhibition.[6][7] 

Epidemiology

Lichen nitidus is an uncommon inflammatory dermatosis that most frequently affects children and young adults, although cases have been reported across all age groups, including older adults.[2][3] The condition appears to occur with similar frequency in both sexes and does not demonstrate a consistent racial or ethnic predilection.[4]

Pathophysiology

Lichen nitidus is a chronic inflammatory condition with distinct clinical and histopathological features but unclear pathophysiology.[1][2] Although the pathophysiology is unclear, lichen nitidus may result from an underlying immune mechanism or may be associated with immune alterations.[1][3] Reports have described lichen nitidus associated with other cutaneous diseases, including lichen planus, erythema nodosum, vitiligo, and lichen spinulosus.[1] The suggested pathophysiology is that an allergen may activate antigen-presenting cells (Langerhans cells), triggering a cell-mediated response and leading to lymphocyte accumulation that forms the discrete inflammatory papules seen in lichen nitidus, which contain many Langerhans cells.[8] Additionally, in theory, viruses, mycobacteria, treponemal species, streptococci, and other active infectious agents could activate a cell-mediated response, leading to the accumulation of lymphocytes and the formation of the inflammatory papules seen in lichen nitidus.[1]

Histopathology

Lichen nitidus has distinct histopathological characteristics. The hallmark of lichen nitidus is a well-circumscribed granulomatous infiltrate of lymphocytes, macrophages, Langerhans giant cells, and multinucleated epithelioid histiocytes in the papillary dermis bordered by extensions of epidermal ridges. This sharply circumscribed inflammatory infiltrate generally spans 4 to 5 dermal papillae within the dermis, giving a ball-in-clutch configuration.[1][3][4][9][10][11] Early lichen nitidus lesions have more lymphocytes, whereas later lesions are more granulomatous and may include occasional giant cells.[3] The epidermis is thinned and parakeratotic with hydropic degeneration of basal keratinocytes and cytoid bodies.[3][10] Generalized purpuric lichen nitidus has the same histopathological features as lichen nitidus, with subepidermal hemorrhages.[6] 

Reports have suggested that lichen nitidus is a variant of lichen planus, but both cutaneous conditions have distinct histopathological features. Lichen planus has more uniform lymphocytes within the infiltrate, which are mostly T helper cells (CD4+). Both conditions have inflammatory changes: a ball-in-claw configuration involving the stratum spinosum, a thinned epidermis, and hyperkeratotic papules. However, parakeratotic papules are present in lichen nitidus, whereas orthokeratotic papules occur in lichen planus.[3]

History and Physical

Lichen nitidus usually presents as asymptomatic, shiny, flat-topped, fleshy pink-to-dark-brown papules. Lesions typically measure 1 to 2 mm in diameter. In patients with darker skin, lesions may appear lighter.[11] Facial hypopigmentation has been increasingly recognized as an atypical manifestation of lichen nitidus in patients with darker skin, particularly among pediatric populations.[12] Lesions commonly present on the neck, trunk, extremities, abdomen, and penile shaft. Involvement of the mucous membranes, palms, soles, and nails is rare, but cases have been reported.[2][3][4] If lichen nitidus is symptomatic, patients primarily report mild sporadic pruritus.[3] Koebner phenomenon is a hallmark of lichen nitidus, as seen in lichen planus, but is not present in all cases.[3][4] 

Rarely, lichen nitidus presents only on the palms and soles and usually occurs alongside lesions in other locations;[13] however, one case report described isolated palmar lichen nitidus.[14] Perforating lichen nitidus represents an exceptionally rare variant, with approximately 11 cases reported worldwide, and has been described in association with atopic dermatitis. Notably, findings from a reported case demonstrated progression of perforating lichen nitidus lesions despite effective dupilumab therapy for underlying atopic dermatitis, suggesting a distinct, potentially unique pathophysiologic mechanism.[15] In addition, a rare presentation of generalized follicular spinous lichen nitidus accompanied by perifollicular granuloma formation has been reported, further expanding the clinical spectrum of this condition and highlighting its potential to create diagnostic uncertainty.[16]

If lesions are present in the oral mucosa, they appear as flat, grayish papules.[3][17] Nail involvement is rare but may present with longitudinal furrowing and ridging of the nail plate due to inflammation of the nail matrix. Nail involvement usually presents with the generalized variant of lichen nitidus, and patients are more likely to have palmar involvement. If the nail fold is involved, nonspecific periungual inflammation or violaceous shiny papules can be seen.[2] Thickening, ridging, pitting, or detachment can also occur in affected nails.[17] Reported variants of lichen nitidus include the following:

• Confluent
• Hemorrhagic
• Linear
• Perforating
• Spinous follicular
• Vesicular 
• Generalized 
• Actinic [1][4]

Purpuric lichen nitidus (hemorrhagic) is rare and presents with red-brown papules due to underlying hemorrhage within the lesions. Cases have been reported in patients with features similar to pigmented purpuric dermatosis.[6] Purpuric generalized lichen nitidus is very uncommon. Histologically, subepidermal hemorrhages within lesions are noted. Degenerative changes occur within capillary vessels, which explains the extravasation of erythrocytes.[18] 

Actinic lichen nitidus usually presents as pinpoint lichenoid papules in photodistributed areas. This variant commonly presents in both pediatric and adult patients with Fitzpatrick skin types IV to VI. Actinic lichen nitidus characteristically demonstrates annular plaques and can have similar histological features to lichen planus. This condition is thought to be a variant of polymorphous light eruption.[4][19] Lichen nitidus in a linear distribution can mimic lichen spinulosus.[1]

Evaluation

The diagnosis of lichen nitidus can be made clinically. Skin biopsy provides a definitive diagnosis and has distinct histopathological features, as mentioned above. 

Dermoscopy

Dermoscopy can be a useful tool in the clinical diagnosis of lichen nitidus. Smooth, white, well-circumscribed 1- to 2-mm circular areas are seen with a reflected brown shadow. The well-circumscribed white circles can correlate with the epidermal acanthosis seen on histopathology. The reflected brownish shadow corresponds to the underlying epithelioid cells and lymphocytes in the dermal papilla. Dermoscopy can help differentiate lichen nitidus from other cutaneous conditions.[9] In patients with palmoplantar involvement, hyperkeratotic pits and well-defined depressions with thin scale have been noted on dermoscopic assessment.[13]

Treatment / Management

Patients are usually asymptomatic, and lesions usually resolve within months to a year. Treatment is usually reserved for symptomatic or cosmetically disturbing lesions.[2][3] Reported treatment options include the following:(B3)

• Topical corticosteroids
• Systemic corticosteroids
• Topical calcineurin inhibitors (tacrolimus)
• Acitretin
• Narrow UVB rays
• Photochemotherapy with psoralen plus ultraviolet A (PUVA)
• H₁ receptor antagonist 
• Astemizole
• Dinitrochlorobenzene immunotherapy 
• Itraconazole
• Isoniazid
• Cyclosporine
• Systemic isotretinoin [6][8][17][20]
(B3)

In chronic or persistent forms of lichen nitidus, topical or systemic corticosteroids are options.[3] In patients with generalized lichen nitidus, resolution is less predictable.[8] PUVA is effective for generalized involvement of the upper and lower extremities.[3] Topical or systemic corticosteroids, astemizole, and dinitrochlorobenzene immunotherapy have also been reported as effective treatment options for generalized lichen nitidus.[8](B3)

Acitretin has been reported to have good results in patients with involvement of the palms and soles.[3] If nail involvement is present, intramatricial corticosteroid injections are a treatment option.[2] Narrowband UVB has a lower carcinogenic risk than broadband UVB or PUVA. The mechanism of treatment is unknown, but it is thought to impair cellular immunity by depleting epidermal Langerhans cells.[8](B3)

Cyclosporine was also reported in rare case reports as beneficial for generalized purpuric lichen nitidus.[6][21] Results from a case report described successful treatment with systemic isotretinoin. Retinoids are thought to suppress inflammation by reducing the migration of neutrophils and eosinophils to the dermis and to have antiproliferative effects. The reported dosage was isotretinoin 40 mg daily, and researchers noted regression after 4 months. This case involved a patient who had cosmetic concerns and diffuse pruritus.[20] The papules seen in lichen nitidus can lead to postinflammatory hyperpigmentation, which usually resolves within a few months.[17](B3)

Differential Diagnosis

Differential diagnoses include but are not limited to lichen planus, keratosis pilaris, follicular eczema, lichen sclerosus et atrophicus, lichen spinulosus, and pigmented purpuric dermatosis.[1][4][6][9]

Prognosis

Lichen nitidus is a self-limiting dermatosis that is usually asymptomatic and does not require treatment. Lesions usually resolve within months to 1 year.[3] If lichen nitidus becomes symptomatic or is cosmetically disturbing, the treatment options described above may be used.[2]

Complications

Lichen nitidus is usually asymptomatic. Occasionally, lesions can be mildly pruritic or affect the nails, palms, soles, and mucosa. Treatment is usually unnecessary, and lesions typically resolve within months to 1 year.[3]