Reactive arthritis (ReA, formerly known as Reiter’s syndrome) is a seronegative spondyloarthropathy characterized by the classic triad of urethritis, conjunctivitis, and arthritis. Although more commonly seen in adult males, many cases have been reported in children. ReA usually arises several weeks after a sexually transmitted infection (endemic) or diarrheal illness (epidemic). Epidemic cases are far more common in the pediatric population. HLA antigen haplotype-B27 (HLA-B27)-positive individuals make up 60–80 % of patients, and they have more frequent skin findings. Involvement of the heart, kidneys, and CNS is rare in ReA. Chronic disease occurs less often in children.

Diagnosis is based on the clinical picture, which may be difficult as only one-third of patients present with the classic triad. Symptoms may be separated by years, although fever and vague constitutional symptoms may provide clues to the diagnosis. Several specific mucocutaneous manifestations, when present, may be diagnostically helpful. Keratoderma blenorrhagicum is the most “classic” (albeit rare) cutaneous finding, appearing as psoriasiform and hyperkeratotic papules, pustules, and plaques most commonly on the palms and soles. Circinate balanitis/vulvitis is more common and is rarely seen outside of ReA, with well-demarcated erosions (females and circumcised males) or hyperkeratotic plaques (circumcised males) on the genitalia. Ocular and urogenital symptoms are common, while painless oral and psoriatic nail changes may occur.

Most studies of ReA have focused on treating the arthritis, not mucocutaneous findings. Management is multidisciplinary, centered on treating the triggering infection and managing symptoms. No consensus exists regarding the benefit of antibiotics, but positive serologies should be treated. For patients in whom a urogenital infection is found, sexual partners also require treatment. NSAIDs are the mainstay of initial arthritis treatment, with immune-modifying therapies used for recalcitrant disease. Further discussion regarding treatment of arthritis and other non-cutaneous symptoms is beyond the scope of this chapter. Treatment of mucocutaneous lesions can largely be achieved with topical therapy, although systemic treatments may be helpful in recalcitrant or severe disease.

Septic arthritis is always in the differential for mono- or oligoarthritis, and should be ruled out with joint aspiration and blood cultures. Serologies for common ReA pathogens, such as Chlamydia trachomatis. Neisseria gonorrhea, Mycoplasma genitalium, Yersinia, Salmonella, Shigella, and Campylobacter jejuni, should be assessed. HIV testing is warranted when disease onset is severe and sudden. ESR and CRP may be elevated, while rheumatoid factor and ANA must be negative. HLA-B27 typing assists in prognosis, as positive patients have a greater risk of chronic disease. If risk factors for tuberculosis (TB) are present, diagnostic testing should be performed, as there are a few case reports of TB-associated ReA.

There has been success with topical steroids ranging from class VII to class I. Salicylic acid aids in the penetration of corticosteroids. One combination of topical salicylic acid and hydrocortisone plus oral aspirin (concentrations/dosages not given) resulted in complete remission in a 6-year-old girl, with clearing of skin lesions within 3 weeks [11]. Topical tacrolimus, calcipotriene, and tazarotene have been effective in treating skin disease for several adults already on systemic therapy [12, 13]

Sulfasalazine can induce remission if started within 3 months of onset [14]. Methotrexate is particularly effective for persistent skin symptoms [15]. One adult patient with circinate balanitis recalcitrant to class I topical corticosteroids responded within weeks to dapsone plus tacrolimus ointment, but was unable to wean off either therapy [16].

Acitretin and etretinate are especially effective and safe in HIV-positive patients based on adult studies [15]. Cyclosporine treatment was successful in one patient who failed etretinate [17]. Anti-TNF therapies have also shown benefit, particularly when used in combination with other systemic treatments like methotrexate [18].

Pityriasis rubra pilaris (PRP) is a papulosquamous disorder characterized by well-demarcated orange-red plaques, follicular keratosis, and palmoplantar involvement, often with “islands of sparing” within lesions (Fig. 4.4). Other findings include furfuraceous scaling of the scalp, yellow-brown discoloration and thickening of the nails, subungual hyperkeratosis, and splinter hemorrhages [19]. Ectropion and erythroderma can be serious complications. Unlike the adult form, pediatric PRP may show a predilection for males over females (3:2). Acute illness or trauma may precipitate the disease. PRP is a clinical diagnosis that may be supported by histopathology that shows acantholysis, an acanthotic epidermis with alternating orthokeratosis and parakeratosis in both vertical and horizontal directions, and follicular plugging.

Griffiths’ classification is most commonly used to describe the different forms of PRP. Types I and II encompass adult disease. A description of the different types affecting children can be found in Table 4.7. Type III is the most common type in children, and is identical to type I in adults. Types IV (Fig. 4.5) and V are less common forms of the disease, and do not always fit the classic description of PRP. Type VI was not part of Griffiths’ original classification, but has been proposed to encompass cases associated with HIV infection.

No randomized, controlled trials exist in either the pediatric or adult literature evaluating treatment options for PRP and thus, recommendations are based on retrospective reviews and case reports. Initial treatment includes topical corticosteroids, keratolytics, and retinoids. If control cannot be achieved with topical therapies, oral retinoids are the preferred treatment. Immunomodulating drugs are an option if retinoids fail or have intolerable side effects. Timing of phototherapy initiation is unclear due to mixed results. Pruritus can be lessened with oral antihistamines or, in refractory cases, topical capsaicin has been used. Spontaneous resolution is possible, even likely, in type III patients within 1–3 years. For HIV-associated disease, highly active retroviral medications are required [20].

As PRP can be associated with HIV, all patients with risk factors or other symptoms should undergo HIV testing. Classic histology showed alternating ortho- and parakeratosis, hypergranulosis, and a predominantly lymphocytic sparse superficial perivascular infiltrate. Laboratory evaluation is only required for systemic therapies and varies by drug (oral retinoids and TNF inhibitors shown here).

Initial treatment for PRP should focus on topical therapies. Several case reports have shown complete response to topical corticosteroids, ranging from low to high potency [21]. Single case reports of different topical retinoids have also shown efficacy [22, 23]. One adult case report demonstrated clearance with pimecrolimus cream [24].

Systemic therapies should be considered after failure of topical treatment or for more severe or diffuse disease, with topical therapies often continued as adjuncts. Retinoids are the mainstay of systemic treatment, with isotretinoin being the most commonly used in children [25]. Treatment with vitamin A or topical calcipotriene has shown benefit in single case reports [26, 27], but other reports contradict these findings. Phototherapy may be beneficial but may also aggravate PRP [28]. It should be reserved for cases refractory to retinoids and topical therapy. Goeckerman treatment, while effective in a few case reports, is not as commonly used.

Immunomodulating drugs show great promise for recalcitrant disease. There are a few case reports and one retrospective review of children receiving TNF inhibitors without significant side effects [29]. Numerous reports show no benefit with methotrexate, although one case report at an unspecified “low dose” was successful. Cyclosporine was effective in a single pediatric patient [30]. Fumaric acid treatment is currently only available in Europe [28].

Pityriasis lichenoides (PL) is an uncommon, acquired dermatosis encompassing a spectrum of disease states, with pityriasis lichenoids et varioliformis acuta (PLEVA) at one end and pityriasis lichenoides chronica (PLC) at the other. PL has a slight male predominance. Acute versus chronic describes the development of lesions, and not necessarily the disease course [31]. Overlap between PLC and PLEVA is common within the same patient. Etiology is unknown, although numerous viral triggers have been proposed and several viruses cultured from affected patients. Currently, PL is felt to lie at the benign end of a spectrum of clonal T-cell disorders. There are a few reports of PL progressing to cutaneous T-cell lymphoma, although some cases may have initially been misdiagnosed as being more benign. Differentiation of PLEVA from lymphomatoid papulosis is important (see section “Lymphomatoid Papulosis”).

Diagnosis can be made clinically, but histology may be helpful for confirmation. Pruritus occurs in half of patients, while skin tenderness is rare. PLEVA begins as an acute, generalized eruption of papules that develop necrosis and form hemorrhagic crusts, with the potential for varioliform scars (Fig. 4.6). Mild constitutional symptoms may exist. A rare and severe subtype, febrile ulceronectrotic Mucha-Habermann disease (FUMHD), shows rapid and coalescent necrosis of skin lesions, severe systemic symptoms, and potential mucous membrane involvement. Fatalities have only been reported in adults. PLC consists of small, scaly, red to brown, polymorphic papules and plaques (Fig. 4.7). The lesions may occur in crops or continuously over time, leaving post-inflammatory dyspigmentation.

No randomized, controlled trials have evaluated PL treatment options, with recommendations based on retrospective reviews and case reports. PLEVA usually runs a self-limited course, whereas PLC often relapses and remits over years. However, chronic disease and spontaneous remission are seen across the spectrum of disease, making treatment efficacy difficult to assess. Patients younger than 4 years of age may have a higher rate of relapse. Pediatric patients tend to have a longer disease course compared to adults, and residual dyspigmentation is more common [32].

Although mid- to high-potency topical corticosteroids and antihistamines may help pruritus, they do not alter the disease course. Phototherapy and oral antibiotics are the two mainstays for initial treatment. Refractory disease may be treated with methotrexate or the addition of acitretin. Slow tapering to prevent relapse is critical for all treatment plans.

No consensus exists regarding the use of laboratory testing for diagnosis or follow-up of PL. The exception is FUMHD, as these patients are critically ill with multi-organ damage and secondary infections requiring close management. In other types, an infectious workup is obtained only if warranted by the history. If workup is positive, treatment should be directed accordingly.

Phototherapy, usually nbUVB, is first-line treatment for PL [33, 34]. Number of treatments and total dose varies widely, with disagreement regarding maintenance. One retrospective study showed no benefit to concomitant systemic medications [34]. Oral antibiotics are first-line therapies as well, especially when phototherapy is not feasible. Traditionally, oral erythromycin is prescribed, but azithromycin is a newer option [35, 36]. Tetracyclines are reserved for patients older than 8 years of age. First-line treatment for FUMHD should include early initiation of high-dose corticosteroids and methotrexate, along with inpatient monitoring, aggressive wound management and debridement, and supportive care [37].

Methotrexate is second-line treatment for patients with unresponsive, severe disease. According to one study, 20 % of patients responded to PUVA alone, and addition of acitretin may provide additional benefit [38]. Topical tacrolimus, both as monotherapy and with azithromycin, showed promise in a few individual case reports [36].

Bromelain is a supplement that should only be considered in patients who refuse traditional medical therapy [39]. One case report of a child with FUMHD and CNS vasculitis responded to the addition of IV cyclophosphamide [40]. Individual adult case reports of several other treatments for FUMHD show varying success.

Lymphomatoid papulosis (LyP) is a lymphoproliferative disease of CD30-positive T-cells, and is rarely seen in the pediatric population. It exists on a spectrum of clonal T-cell disorders, with malignant histologic characteristics but usually a benign clinical course. It may co-occur with lesions of PL or anaplastic large-cell lymphoma (ALCL). The disease displays three classic histologic subtypes, with two more recently proposed (see Table 4.14) [41]. Type A is the most common, with type B being uncommon and types C-E very rare. These subtypes all appear the same clinically, and have not been shown to affect disease course in pediatric patients. There are conflicting reports of CD4 versus CD8 predominance in children [42, 43]. While LyP lesions themselves are benign, they can be associated with lymphoma and hematologic malignancies. Although the risk is far lower than in adults with the disease, a few cases of lymphoma have been reported in affected children decades after onset, necessitating lifelong follow-up. There is a lower incidence of T-cell clonality in pediatric patients, which may account for the better prognosis.

Classic LyP lesions consist of erythematous papules and nodules, sometimes with central ulceration. Patients suffer from cyclic eruptions that last anywhere from 2 to 8 weeks if untreated, and multiple locations are often involved. They may report a preceding viral illness. The disease can be confused with PLEVA, but LyP lesions are usually fewer and larger, with the average age of onset between 7 and 9 years. Lesions may be pruritic or tender, and often leave behind scars. The tongue may rarely be involved. LyP can be difficult to differentiate from insect bites, especially when eosinophilia is present on histology. Singular lesions can also be mistaken for primary cutaneous ALCL.

If lesions are limited in number, it is reasonable not to treat while maintaining close follow-up. More numerous lesions or those in cosmetically sensitive areas should be treated due to risk of scarring. In these cases, first line treatments in children include topical corticosteroids and judiciously increasing sun exposure. For more severe, symptomatic, or widespread cases, methotrexate and phototherapy are the best options. Recurrences are common no matter the treatment employed, although rare cases of complete resolution have been reported. Oral corticosteroids are not beneficial.