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Dermatology Diagnosis

Addressing Onycholysis And Periungual Inflammation In A Patient With Malar Rash, Discoid Skin Lesions And Joint Pain

A 35-year-old female presented to our clinic with a concern of “ingrowing toenails.” The patient reported pain and inflammation surrounding the first, second and third toenails of her right foot as well as the second toe of her left foot. She reported that her right second toenail had fallen off several times. The patient denied a history of trauma. Additionally, she related thickening and discoloration of both great toenails. Past treatment included a course of oral azithromycin prescribed by her primary care physician. The patient reported no improvement with oral antibiotic therapy.

The physical examination revealed onycholysis of the second toenail with hyperkeratosis of the nail bed. The hallux nails were yellow, thick and dystrophic. The second nail on the left foot exhibited transverse depression, which was consistent with Beau’s lines. There was periungual erythema, prominent nail fold capillaries and vascular congestion of the proximal, medial and lateral nail folds of the affected digits. There was pain on palpation of all the affected nail plates and adjacent soft tissue. The nails did not exhibit any ingrowing nail borders or signs of bacterial infection. In addition to these nail changes, the patient had darkly discolored, tender papules present on the dorsum of the foot bilaterally.

The patient’s past medical history included systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE). Symptoms related to her systemic lupus erythematosus included a malar facial rash, discoid skin lesions, nephritis, arthralgias and Raynaud’s phenomenon. At the time of clinical presentation, the patient was under the care of a rheumatologist and a dermatologist, and receiving treatment consisting of belimumab and prednisone for systemic lupus erythematosus and intralesional triamcinolone injections for the discoid lupus erythematosus.

What You Should Know About Lupus Erythematosus

Systemic lupus erythematosus is a systemic autoimmune disorder resulting from polyclonal B-cell activation and autoantibody production. The disorder most commonly presents in women of childbearing age. The disorder has an extremely diverse spectrum of clinical presentations ranging from limited cutaneous disease (cutaneous lupus erythematosus) to potentially lethal systemic manifestations such as uremia or progressive central nervous system involvement.1 The classic triad of systemic lupus erythematosus includes fever, joint pain and rash.1,2

Cutaneous lupus erythematosus (CLE) affects the skin and dermal structures, including the hair and nails. Cutaneous lupus erythematosus can be divided into skin lesions that are histologically specific for lupus erythematosus and those that are non-specific. Additionally, one can divide cutaneous lupus erythematosus into acute, subacute and chronic or discoid lupus erythematosus subtypes. Cutaneous lupus erythematosus can occur in isolation or it can be associated with systemic disease. Most commonly, acute cutaneous lupus erythematosus is associated with systemic disease while chronic discoid lupus occurs without underlying organ involvement. Healy and colleagues report only a five percent rate of progression of discoid lupus erythematosus to systemic lupus erythematosus.3

What The Literature Reveals About Nail Abnormalities With Systemic Lupus Erythematosus

Numerous disorders of nail and nail apparatus reportedly occur in association with systemic lupus erythematosus. Nail changes occur in over 25 percent of patients with systemic lupus erythematosus.4,5 Onycholysis and nail bed hyperkeratosis are the most common nail disorders associated with systemic lupus erythematosus.4 Nail bed hyperkeratosis is associated with discoid lupus erythematosus. Periungual erythema with prominent nail fold capillaries, vascular infarction and red lunulae are other common features of systemic lupus erythematosus.6-8 Other less frequent nail abnormalities associated with systemic lupus erythematosus include splinter hemorrhage, pincer nail deformity, leukonychia and Beau’s lines.6,9-11 Systemic lupus erythematosus-associated nail disorders frequently occur in patients who also have Raynaud’s phenomenon and mucous membrane ulcerations.5

Raynaud’s phenomenon is commonly associated with systemic lupus erythematosus and can affect the digits, especially in colder climates. Raynaud’s phenomenon can contribute to periungual discoloration and pain. Vasculopathy is another common feature of systemic lupus erythematosus that can affect the nail and nail unit. Vasculopathic lesions of the nail unit can occur secondary to blood vessel infarction and/or cutaneous hemorrhage of the nail fold. These disorders result from vasculitis or platelet thrombi of the small digital vessels.12
Histopathologic analysis of the nail folds affected by lupus erythematosus show numerous changes including hyperkeratosis, degeneration of the basal cell layer, lymphocytic infiltrate of the dermis, edema and capillary dilation.12 Nail bed changes include hyperorthokeratosis, development of a granular cell layer, basal cell edema and hyaline bodies.12 These histopathologic changes are not diagnostic for lupus erythematosus and nail bed and nail apparatus biopsy are not routine in the workup of lupus erythematosus. Biopsy can be beneficial, however, in distinguishing lupus-induced nail pathology from drug-induced or other common nail abnormalities.

Relevant Insights On Treatment And Prognosis

The prognosis for systemic lupus erythematosus is highly variable. Disease severity can range from benign to rapidly progressive and potentially fatal. Systemic lupus erythematosus can have periods of quiescence and flares throughout a patient’s lifetime. Isolated skin and musculoskeletal involvement are associated with milder disease and a higher survival rate in comparison to individuals with renal and central nervous system involvement.13,14 Skin and nail disorders typically reflect underlying systemic lupus erythematosus disease activity with worsening skin and nail pathology in more active disease states.12 Splinter hemorrhages are the nail change most closely linked to disease activity.15

Treating the underlying condition is the mainstay of the treatment of cutaneous disorders associated with systemic lupus erythematosus. Standard therapy for systemic lupus erythematosus includes steroids as well as non-biologic disease-modifying anti-rheumatic drugs (DMARDS) such as hydroxychloroquine, azathioprine and methotrexate. Two biologic DMARD therapies, belimumab (Benlysta®, GlaxoSmithKline) and rituximab (Rituxan®, Genentech), have been proven effective in the treatment of lupus erythematosus. Belimumab is a B-lymphocyte stimulator inhibitor that reduces disease activity, flares and steroid use.16 Rituximab, a chimeric monoclonal antibody to CD20 on B-cells that triggers cell death, has also proven beneficial in the treatment of refractory cases of systemic lupus erythematosus.17

While there are numerous treatment modalities for nail pathology associated with systemic lupus erythematosus, there is a paucity of research examining the efficacy of these options.

Vanhooteghem and colleagues found that systemic corticosteroids, retinoids and antimalarials were effective in resolving nail bed hyperkeratosis in a patient with systemic lupus erythematosus and discoid lupus erythematosus.18 Protective measures including cold avoidance and smoking cessation can help with Raynaud’s phenomenon and vasculopathic skin and nail changes. Vasodilators and inhibitors of platelet aggregation such as aspirin and nifedipine may be effective in improving digital blood flow.12

In Conclusion

It is difficult to determine with certainty the etiology of many nail and nail apparatus disorders associated with systemic lupus erythematosus. Immunosuppressant medications used for the management of systemic lupus erythematosus may predispose patients to bacterial and fungal infections of the nail and surrounding soft tissues. Other common, unrelated nail disorders may have similar characteristics as well. Despite this, systemic lupus erythematosus-associated nail and nail apparatus disorders can be important indicators of disease and reflections of underlying disease activity.

Dr. Hoffman is an Attending Physician in the Department of Orthopedics at Denver Health Medical Center. She is an Assistant Professor in the Department of Orthopedics at the University of Colorado School of Medicine. She is an Attending Physician for the Highland/Presbyterian St. Luke’s Medical Center Residency Program.

Dermatology Diagnosis
By Kristine Hoffman DPM, FACFAS

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3.    Healy E, Kieran E, Rogers S. Cutaneous lupus erythematosus--a study of clinical and laboratory prognostic factors in 65 patients. Ir J Med Sci. 1995;164(2):113-115.

4.    Richert B, Andre J, Bourguignon R, de la Brassinne M. Hyperkeratotic nail discoid lupus erythematosus evolving towards systemic lupus erythematosus: therapeutic difficulties. J Eur Acad Dermatol Venereol. 2004;18(6):728-730.

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9.    Friedman SJ. Leukonychia striata associated with systemic lupus erythematosus. J Am Acad Derm. 1986;15(3):536-538.

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11.    Twigg EV, Weitz NA, Scher RK, Grossman ME. Pincer nails in a patient with systemic lupus erythematosus and lupus nephritis: A case report. JAAD Case Rep. 2016;2(3):233-235.

12.    Trueb RM. Involvement of scalp and nails in lupus erythematosus. Lupus. 2010;19(9):1078-1086.

13.    Kasitanon N, Magder LS, Petri M. Predictors of survival in systemic lupus erythematosus. Medicine (Baltimore). 2006;85(3):147-156.

14.    Faurschou M, Dreyer L, Kamper AL, Starklint H, Jacobsen S. Long-term mortality and renal outcome in a cohort of 100 patients with lupus nephritis. Arthritis Care Res (Hoboken). 2010;62(6):873-880.

15.    Tunc SE, Ertam I, Pirildar T, Turk T, Ozturk M, Doganavsargil E. Nail changes in connective tissue diseases: do nail changes provide clues for the diagnosis? J Eur Acad Dermatol Venereol. 2007;21(4):497-503.

16.    Navarra SV, Guzman RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721-731.

17.    Hughes G. Rituximab in lupus and beyond: the state of the art. Lupus. 2009;18(7):639-644.

18.    Vanhooteghem O, Henrijean A, Richert B, De La Brassinne M. [Hereditary osteo-onychodysplasia (nail patella syndrome)]. Ann Dermatol Venereol. 2001;128(10 Pt 1):1063-1067.

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