Persistent rash not affected by steroids

On exam, the patient appeared well nourished and interactive. He was noted to have several inflammatory and slightly indurated red-to-violaceous patches, varying in size from 1 to 5 cm, on his lower abdomen, lower back, buttocks, and proximal thighs. Numerous...

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On exam, the patient appeared well nourished and interactive. He was noted to have several inflammatory and slightly indurated red-to-violaceous patches, varying in size from 1 to 5 cm, on his lower abdomen, lower back, buttocks, and proximal thighs. Numerous hypopigmented, slightly scaling plaques were also found on the boy’s mid-back and thighs. No palpable lymphadenopathy was noted.  Given the history of a persistent rash despite treatment with potent topical steroids, a decision was made to perform a 2-mm punch biopsy to one of the inflammatory patches.

Hematoxylin and eosin stain revealed a lichenoid dermatitis with epidermotrophic lymphocytes (infiltration into the overlying epidermis). This pattern of inflammation is highly suspicious for mycosis fungoides (MF), a form of cutaneous T-cell lymphoma (CTCL). Repeat shave biopsies were done to confirm the diagnosis and to rule out lichen sclerosus et atrophicus and lichen striatus, both of which can mimic MF histologically. Repeat biopsies showed a patchy lichenoid dermatitis with intra-epidermal mononuclear cells and slight spongiosis, supporting a diagnosis of MF. Gene-rearrangement studies were performed to complete the workup, and the results were positive for T-cell-receptor-gamma gene rearrangement.

MF is the most common of the CTCLs, with an estimated incidence of 1 in 300,000 yearly.¹ CTCL describes a group of malignant lymphomas of T-cell origin with primary manifestations in the skin. First documented in 1806, MF was given its name because the rash sometimes resembled a mushroom-like fungal disease.

MF is characterized by the expansion of a clone of CD4+/memory helper T cells that normally patrol the skin. Although the etiology remains unknown, it is speculated that chronic exposure to an antigen may lead to development of a malignant clone. This may explain the slightly increased incidence of MF in patients with atopic dermatitis.² A study in Israel found familial clustering of MF within eight families, suggesting a possible immunogenetic basis for the disease.³

MF occurs more commonly in blacks, men, and the elderly, although the incidence of MF in children appears to be increasing. Early-onset MF is more common among black and Hispanic women.

The following histologic criteria have been proposed for the diagnosis of MF: a bandlike or patchy upper-dermal infiltrate of lymphocytes and other inflammatory cells; epidermotropism of mononuclear cells; little spongiosis of the epidermis; and atypical lymphocytes. The presence of a Pautrier microabscess—a clear halo surrounding an intraepidermal mononuclear cell singly or in clumps—is suggestive but not necessary for the diagnosis.^4,5

Patients often present with a chronic rash that was treated ineffectively. Physical exam of early-stage MF reveals red or brown flat patches, sometimes with an overlying fine scale. In darker-skinned patients patches may appear hypopigmented or hyperpigmented. As the patches become more infiltrated, they evolve into palpable, well-demarcated plaques. Rare variants of MF include hyperkeratotic patches or plaques confined to the palms and soles,⁶ generalized vesiculobullous lesions, papules only,⁷ and persistent pruritus without any rash.⁸ Lesions may appear anywhere on the body but are most frequently located on the lower back, buttocks, groin, and on the breasts in women.

MF develops gradually over several years and has a variety of clinical presentations that may be confused with common benign conditions. To complicate matters further, skin biopsies in the earlier stages of disease are often nonspecific and may resemble those of several dermatoses. Several researchers have deemed MF “the great imitator.”9 A high clinical suspicion and a skilled dermatopathologist are often required to make the correct diagnosis. It is estimated that the median duration from the onset of skin symptoms to diagnosis is three to six years.¹⁰

The tumor-node-metastasis (TNM)-based system stages disease based on skin (primary tumor) and lymph-node involvement. The presence of extracutaneous disease indicates metastases. Stage I disease is limited to the skin only and consists of patchy or plaquelike skin disease. Stage IA disease involves <10% of the skin surface area (T1), and stage IB disease affects >10% of the skin surface area (T2). Stage II disease is defined by the presence of tumors (T3), which frequently appear as red-violet nodules that may be exophytic or ulcerated. Patients with erythroderma (T4) or blood, lymph-node, or other organ involvement are classified as having advanced (Stage III-IV) disease. Peripheral lymphadenopathy is the most frequent site of extracutaneous involvement in mycosis fungoides. Blood status does not affect disease staging.

For patients with disease limited to the skin, treatment consists of phototherapy, local radiation, or such topical medications as steroids, chemotherapy, (nitrogen mustard, carmustine, imiquimod), or retinoids.¹¹ Steroids have been shown to lyse T lymphocytes, block cytokine secretion, and suppress mitosis. The side effect of hypothalamic-pituitary-adrenal axis suppression was noted to be very low and temporary. Topical chemotherapy agents inhibit cell growth and proliferation. Nitrogen mustard (a chemotherapeutic alkylating agent) applied to the skin has been shown to induce an 80% remission rate12 in stage IA disease, although therapy is often limited by intolerance.

Systemic treatment is reserved for more advanced disease and may include immunomodulatory therapy, retinoids, histone deacetylase inhibitors, or chemotherapy. Most commonly, immunomodulator therapy is used to enhance host immune function and gain control of the disease. At times, this may be combined with other treatments that increase malignant cell apoptosis. Patients may also require antipruritic medications to control itching.

Skin stage and the presence or absence of lymphadenopathy remain the most important determinants of clinical outcome.¹³ Because MF is mostly a chronic and slowly progressive condition, complete cure is anticipated only for those with stage IA disease. MF in children usually represents a chronic, low-grade lymphoproliferative disease with the clinical features of a low-grade lymphoma. These patients have an overall life expectancy similar to age- and sex-matched controls. Patients with more advanced disease have a more doubtful prognosis, with a median survival of 3.2 years.¹²

This patient was referred to a pediatric dermatologist for consultation regarding treatment options. Additional workup consisted of a complete blood count (to rule out aggressive disease), comprehensive metabolic profile, and lactate dehydrogenase test, all of which were within normal limits. The boy was started on skin-targeted therapy with topical steroids and phototherapy.  Two to three times per week, the patient exposed his skin (while keeping the genitals covered) to filtered narrow band UVB light; the dosage was increased each session as tolerated. In addition, he applied triamcinolone 0.1% cream daily to the hypo­pigmented patches and desoximetasone 0.25% cream daily to the inflammatory patches.

After one month of treatment, the inflammatory patches had somewhat decreased in size, and the hypopigmented patches showed some evidence of returning pigment. The patient is continuing with this treatment regimen until an absence of skin lesion is noted.

Esther Stern, NP-C, is a family nurse practitioner at Advanced Dermatology & Skin Surgery in Lakewood, N.J. The author has no relationships to disclose relating to the content of this article.

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References

1. Weinstock MA, Horm JW. Mycosis fungoides in the United States. Increasing incidence and descriptive epidemiology. JAMA. 1988;260:42-46.

2. Tuyp E, Burgoyne A, Aitchison T, MacKie R. A case-control study of possible causative factors in mycosis fungoides. Arch Dermatol. 1987;123:196-200.

3. Hodak E, Klein T, Gabay B, et al. Familial mycosis fungoides: report of 6 kindreds and a study of the HLA system. J Am Acad Dermatol. 2005;52:393-402.

4. Massone C, Kodama K, Kerl H, Cerroni L. Histopathologic features of early (patch) lesions of mycosis fungoides: a morphologic study on 745 biopsy specimens from 427 patients. Am J Surg Pathol. 2005;29:550-560.

5. Shapiro PE, Pinto FJ. The histologic spectrum of mycosis fungoides/Sézary syndrome (cutaneous T-cell lymphoma). A review of 222 biopsies, including newly described patterns and the earliest pathologic changes. Am J Surg Pathol. 1994;18:645-667.

6. Kim ST, Jeon YS, Sim HJ, et al. Clinicopathologic features and T-cell receptor gene rearrangement findings of mycosis fungoides palmaris et plantaris. J Am Acad Dermatol. 2006;54:466-471.

7. Kodama K, Fink-Puches R, Massone C, et al. Papular mycosis fungoides: a new clinical variant of early mycosis fungoides. J Am Acad Dermatol. 2005;52:694-698.

8. Pujol RM, Gallardo F, Llistosella E, et al. Invisible mycosis fungoides: a diagnostic challenge. J Am Acad Dermatol. 2002;47(2 Suppl):S168-S171.

9. Zackheim HS, McCalmont TH. Mycosis fungoides: the great imitator. J Am Acad Dermatol. 2002;47:914-918.

10. Reddy K, Bhawan J. Histologic mimickers of mycosis fungoides: a review. J Cutan Pathol. 2007;34:519-525.

11. National Comprehensive Cancer Network (NCCN). NCCN guidelines. Non-Hodgkin’s lymphoma.

12. James WD, Berger TG, Elston DM. Diseases of the skin appendages. In: Andrews’ Diseases of the Skin: Clinical Dermatology. 10th ed. Philadelphia, Pa.: Saunders-Elsevier; 2006:727.

13. Juarez T, Isenhath SN, Polissar NL, et al. Analysis of T-cell receptor gene rearrangement for predicting clinical outcome in patients with cutaneous T-cell lymphoma: a comparison of Southern blot and polymerase chain reaction methods. Arch Dermatol. 2005;141:1107-1113.

All electronic documents accessed March 15, 2011.