A perplexing pruritic papular rash
Published Web Locationhttps://doi.org/10.5070/D30p37871j
A perplexing pruritic papular rash
M D Anderson Cancer Center. firstname.lastname@example.org
Mandy Pinkerton, Staci Ward MD, and Madeleine Duvic MD
Dermatology Online Journal 9(3): 9
Report of a Case
|Figure 1||Figure 2|
|Upper torso and abdomen—Diffuse papular and pustular lesions with marked excoriation secondary to scabies.|
A 57-year-old man presented to the clinic with a 2-month history of a pruritic, papular rash predominately on his thighs, trunk, and neck. He had recently returned from Brazil, where he was treated unsuccessfully for scabies. An immunofluorescence biopsy was consistent with bullous pemphigoid. Despite treatment with topical steroids and antihistamines, the rash continued to spread and the intensity of the pruritus markedly increased to an excruciating level. Past medical history was significant for prostate cancer treated by prostatectomy 4 years ago. He was currently on no medications and had no known drug allergies. Recently, his wife also developed mild pruritus.
|Figure 4||Figure 5|
|Anterior and posterior lower extremities showing multiple papules and pustules with intense inflammation. These images demonstrate the predominance of the lesions closer to the groin.|
On physical exam, the patient was an afebrile, normotensive, well-appearing man. Approximately 20 percent of his body surface area was involved with eythematous macules, papules, and pustules that had coalesced into plaques, sparing the face and webbed spaces of the digits. Excoriated papules were present in the groin and thigh regions. Some of the more recent lesions were follicular and pustular in nature.
Laboratory results revealed a white blood cell count of 7000/mm3, with 67 percent neutrophils, 12 percent lymphocytes, 6 percent monocytes, and 14 percent eosinophils. The hepatitis panel and HIV test were both negative. T-cell panel showed an absolute CD4 of 422, absolute CD8 of 195.
A biopsy revealed an atypical dermal lymphoid infiltrate with epidermotropism suggestive of mycosis fungoides, and molecular PCR analysis revealed a monoclonal T-cell receptor gamma-chain gene rearrangement. An additional biopsy and serum were tested for direct and indirect immunofluorescence and were both negative.
Impetiginized clonal dermatitis and folliculitis secondary to scabies.
Mineral oil scrapings from the patient and his wife were positive for mites under microscopic exam. Skin cultures grew Staphylococcus aureus. The patient was treated with permethrin 5 percent cream for 2 nights for scabies. This treatment was to be administered again in 7-10 days. The patient received specific instructions to wash all of his bedding and clothes in temperatures greater than 140° F and to purchase a vinyl mattress cover and mite-repellent pillow covers.
In addition to permethrin 5 percent cream, the patient required clindamycin, dicloxacillin, oral prednisone, topical steroids, bactroban ointment, and hydroxyzine for relief. After a total of five treatments with permethrin to the skin, the patient was moderately improved. However, he still complained of residual pruritus. The addition of UVB therapy was necessary to resolve his symptoms. The patient was also given one dose of ivermectin. In general, his condition gradually improved over the next month with resolution of the lesions and pruritus. Finally, after 4 months of intense pruritus and spreading papular, pustular lesions, the pesky microscopic mites had been eradicated.
Sarcoptes scabiei, the human scabies mite, is a highly contagious ectoparasite that infects millions of people per year. The female mite burrows into the skin, just below the stratum corneum, where it deposits from two to three eggs per day. Larvae from these eggs hatch after approximately 2 weeks and emerge to the surface to mate. These mites then reinfect the skin.  The majority of lesions are generally symmetrical and initially found on the volar wrists, between the fingers, on the elbows, and on the penis. Other common sites include the belt line, buttocks, thighs, and scrotum. The lesions usually spare the face and neck and are typically small papules and vesicles, often accompanied by plaques, pustules, or nodules.  The appearance of the rash is often altered secondary to a bacterial superinfection or topical steroid use. Most patients will complain of an intense itch especially at night and after a hot shower. The itching has been associated with a hypersensitivity reaction to the excreta that the mite deposits within the burrow.  This burrow often becomes surrounded by infiltrates of eosinophils, lymphocytes, and histiocytes. 
Despite treatment, further lesions may erupt. This finding is common as additional mite larvae hatch. Once the eggs are laid, the larvae continue the life cycle, often reinfecting the patient.  For this reason, repeated treatments are often needed to eradicate the mites. In addition, the rash and itch often persist for days to months after the mite has been eradicated, because the hypersensitivity reaction has been initiated.
The diagnosis of scabies is often difficult. Scabies can be diagnosed by microscopic visualization of the mite, the burrow, the excreta, or the eggs within the skin. The diagnosis becomes complicated in patients who have severe hypersensitivity reactions that result in multiple excoriations or plaques. These findings make visualization of the mite and burrow almost impossible.  At this point, biopsies or scrapings of the papulovesicles may be helpful.
It is important to recognize clinical clues that suggest scabies: linear scale and crusts, shallow burrows, genital papules and nodules, and signs of excoriation. Scrapings and biopsies may reveal refractile, granular, fecal material, eczematoid spongiosis, a perivascular inflammatory infiltrate composed of lymphoreticular cells or eosinophils, and a lymphocytic type vasculitis.  With negative microscopic and pathologic findings, a diagnosis of scabies can be based on clinical presentation and history.
A hypersensitivity reaction, whether mild or severe, most often accompanies the mite infestation and produces the symptoms. Surprisingly, the mite itself provokes very little dermatitis. The rash and itch associated with scabies are usually a manifestation of the immune response. 
The reaction to scabies appears to consist of both type I and type IV hypersensitivity reactions. In the type I reaction, an antigen on the mite encounters specific IgE on mast cells within the epidermis. This interaction leads to mast-cell degranulation causing wheal and flare reactions. The notion that a type I hypersensitivity reaction occurs is supported by evidence of elevated IgE antibody levels among infected patients. Further evidence demonstrates that the IgE antibody levels fall after successful treatment.  Additionally, cross-reactivity between the scabies mite and the house dust mite has been described.  In addition to the type I hypersensitivity reaction, it is well accepted that a cell-mediated type IV delayed hypersensitivity reaction also occurs. Support for a delayed hypersensitivity reaction includes the lack of reactivity in virgin subjects and the latent period observed between infestation and rash.  Often a 10-30 day delay occurs between time of infestation and the first appearance of skin manifestations.  Further evidence for a cell-mediated immune reaction is evident by histopathology. Biopsy often reveals a superficial and deep perivascular mixed inflammatory cell infiltrate composed of lymphocytes (mainly T-cells), histiocytes, and eosinophils. The papillary dermis is edematous and the epidermis may show spongiosis. This histopathology is similar to most other arthropod bites. 
This case was quite perplexing because of the severity of the hypersensitivity reaction that this patient exhibited. Severe hypersensitivity reactions have been reported to trigger monoclonal T-cell infiltration, which can immunohistochemically and microscopically suggest mycosis fungoides and would explain the biopsy that was suggestive of mycosis fungoides. Furthermore, in the early stages of mycosis fungoides, it has been debated whether the disease represents a malignancy or a clonal T-cell response to stimulation by a specific antigen.  In this case, the antigen would be related to the mite.
Even though the exact antigen involved in the hypersensitivity reaction of scabies remains unknown, the importance of understanding the underlying immunology is clear. The clinical appearance and histology may be puzzling. Therefore, to accurately diagnose and treat a patient with scabies, all laboratory, immunohistochemical, and microscopic data must be evaluated in the context of an ongoing hypersensitivity reaction.
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