Treating A Non-Pruritic Rash That Occurred After Antibiotic Use

A 32-year-old male presented to my office with the chief complaint of heel pain. His symptoms were consistent with plantar fasciitis and a strong element of post-static dyskinesia. He had a secondary complaint of a recent rash that developed on his legs after he made the appointment for heel pain. The patient was concerned because the rash became worse over the prior week and there was pain when he touched the affected area.

   His past medical history was remarkable for depression with anxiety disorder and psoriasis. His daily medications included sertraline (Zoloft, Pfizer), doxepin (Sinequan, Pfizer) and hydroxyzine (Vistaril, Pfizer). He denied any drug allergies. The patient’s past surgical history was remarkable for a right ankle fracture repair. His social history revealed that he was married, never smoked, denied any alcohol intake and was employed as a photographer.

   I performed a review of systems and he related a recent tooth abscess and took a penicillin-based antibiotic for that. Approximately three days after taking the antibiotic, he developed joint pain in his knees, feet and right shoulder. The patient then developed the rash on his legs. He related pain but no itching. He recently saw a dermatologist who was “working him up” for the rash. The patient told me his blood work revealed a normal white blood count and normal erythrocyte sedimentation rate.

   The physical examination revealed a well-dressed, well-nourished male in no apparent distress. The vascular exam revealed strong palpable pedal pulses with capillary fill time immediate to the level of the toes. The neurologic exam revealed symmetric deep tendon reflexes and epicritic sensation intact to the toes.

   The dermatologic exam revealed skin texture, temperature and turgor within normal limits. On the anterior surface of his legs, just proximal to the knees, there were erythematous plaques. No scale, blistering or central clearing of the lesions (i.e. targeted lesion) were present.

   The orthopedic exam revealed symmetric, pain-free range of motion of the ankle, subtalar and midtarsal joints. There was tenderness with palpation of the plantar medial tuber of both heels including the central band of the plantar fascia. He had no pain with side-to-side compression of the heels. A complete set of foot radiographs revealed a small plantar heel spur. There was no acute fracture, tumor or dislocation present.

Key Questions To Consider

1. What are the characteristic features of this condition?
2. What is the most likely diagnosis?
3. What is your differential diagnosis?
4. What would advanced diagnostic testing include?
5. What is the treatment of this condition?

Answering The Key Diagnostic Questions

1. Characteristic features include a tender, erythematous patch, nodule or plaque that is usually located on the pre-tibial region of the shins. The patient also lacked a high fever and had no signs of leukocytosis, blistering or central clearing of the lesions, or pruritus. He had a recent infection treated with a penicillin-based antibiotic.
2. Erythema nodosum
3. Tender erythematous nodules/plaques including cellulitis, erysipelas, insect bites, erythema nodosum, nodular vasculitis, superficial thrombophlebitis, Sweet’s syndrome and acute urticaria
4. Further testing may include a punch biopsy of the lesion, complete blood count, antistreptolysin-O titer, throat culture, tuberculin test or a chest X-ray.
5. The treatment includes cool compresses on the lesions, anti-inflammatory medications and bed rest.

A Closer Look At The Differential Diagnoses

His orthopedic condition was plantar fasciitis and standard treatment for that began with a stretching and icing protocol, supportive shoes and a non-steroidal anti-inflammatory drug (NSAID).

   For his dermatologic condition, the differential diagnosis of tender erythematous nodules/plaques includes cellulitis/erysipelas, insect bites, erythema nodosum, nodular vasculitis, superficial thrombophlebitis, Sweet’s syndrome and acute urticaria.

   Erysipelas is a skin infection that causes cellulitis. The infection involves the superficial layers of the skin. Clinically, the plaque is well demarcated with intense erythema. The affected area is usually indurated. Erysipelas is commonly the result of group A Streptococcus bacteria. Risk factors include skin breakdown (cuts, blisters, ulcers, erosions, etc.). Venous insufficiency or lymphedema may cause leg swelling and eventual skin breakdown causing cellulitis. Blistering is common with venous stasis cellulitis. Fever, chills and malaise may also occur.

   Insect bites and stings can cause a well-demarcated erythematous plaque. Ascertaining the clinical history is paramount to distinguish this from other causes. Insect bites rarely lead to cellulitis. Pruritus is typically associated with insect bites.
Erythema nodosum is a panniculitis (inflammatory condition affecting the subcutaneous tissues). The lesion associated with erythema nodosum is a tender, erythematous patch, nodule or plaque that is usually on the pre-tibial region of the shins. Initially, the skin lesions appear red. As they age, the lesions may become bruised looking in appearance with a violaceous, brown or even yellowish/green color.

   Associated clinical symptoms may include fever, chills, malaise and joint pains. Causation may be idiopathic. However, the majority of the cases are caused by infections, drug reactions or autoimmune disorders. The common infectious causes include tuberculosis, Valley fever (coccidioidomycosis), Streptococcus, hepatitis C, Epstein-Barr virus and Yersinia. Drug-induced erythema nodosum may be caused by oral contraceptives, sulfonamides, vaccinations and NSAIDs (including salicylates), tetracyclines, barbiturates, and it may occur after oral steroid use tapers off.

   Autoimmune disorders associated with erythema nodosum include inflammatory bowel disease such as ulcerative colitis and Behçet’s disease. There is a known link between erythema nodosum and granulomatous pulmonary diseases such as tuberculosis, sarcoidosis and coccidioidomycosis.

   Nodular vasculitis is typically sequelae of tuberculosis. The lesions appear as groupings of small tender erythematous nodules on the legs including the calves and shins.

   Superficial thrombophlebitis is an inflammatory condition of the superficial veins, which may have small blood clots. Typically, the skin becomes warm, tender and swollen at the level of the vein. A palpable indurated cord is present along the course of the blood vessel.

   Sweet’s syndrome is an acute febrile neutrophilic dermatosis. The skin eruption is a well-demarcated erythematous papule or plaque usually affecting the hands and fingers. Lesions can arise on the arms, legs, neck and head. Lesions may have blisters, pustules and ulcerations. There may be a central clearing appearance (targeted lesion). There may be associated high fever, chills, joint pain, mouth ulcers and conjunctivitis.

   Sweet’s syndrome is usually caused by an underlying systemic condition and may be drug-induced via granulocyte colony-stimulating factor agents such as filgrastim, NSAIDs, oral contraceptives, retinoic acid, sulfa drugs, diazepam and others. The syndrome may also be caused by malignancy, infections, inflammatory bowel disease and pregnancy.

   Urticaria is a vascular reaction of the skin that leads to erythematous plaques, which typically have moderate to severe pruritus. An important clinical feature of the urticarial wheal is the ability of complete blanching with pressure. Urticaria may be the result of food and drug allergies, insect bites and contact hypersensitivities such as latex. Urticaria may also result from medical conditions such as infections, autoimmune disorders, pregnancy, thyroid dysfunction and serum sickness.

What You Should Know About Erythema Nodosum

The correct diagnosis for the patient is erythema nodosum. The etiology was most likely his recent infection or a drug-induced reaction to the antibiotics that he completed. When reviewing the conditions associated with similar rashes, you will note the commonality with etiology. Many of the associated conditions involve drug eruptions (with similar classes of drugs), infections and autoimmune disorders.

   Keys to making the correct diagnosis involved the lack of the following: high fever, leukocytosis, blistering or central clearing of the lesions, and pruritus. Other key factors were his history as a healthy young man with recent infection and the fact that he had completed a course of a penicillin-based antibiotic.

   Erythema nodosum has its peak incidence in 20- to 40-year-olds with a predilection for women. Streptococcal infections are the most common cause of erythema nodosum in children. Drugs, autoimmune diseases and inflammatory bowel diseases (i.e. ulcerative colitis) are typically the causes in adults.

   If there is uncertainty with making the diagnosis based on history and physical exam, standard further testing may include: punch biopsy of the lesion, complete blood count, antistreptolysin-O titer, throat culture, tuberculin test and a chest X-ray to rule out pulmonary diseases such as tuberculosis, sarcoidosis or coccidioidomycosis.

Pertinent Insights On Effective Treatment

Erythema nodosum is a self-limiting condition. Typically, it takes four to eight weeks for the lesions to resolve. Certainly treating the underlying cause (i.e. infection, cancer, inflammatory bowel disease, etc.) is the primary concern. Supportive care such as cool compresses on the lesions, anti-inflammatory medications and rest are sufficient to manage the skin lesions.

   A mnemonic to aid in remembering the causes and treatment for erythema nodosum includes the acronym “BEDREST.” This stands for Behçet’s syndrome, Estrogens, Drugs, Recent infection, Enteropathies, Sarcoidosis and Tuberculosis. Bed rest is also one of the treatments.

   Dr. Fishco is board-certified in foot surgery and reconstructive rearfoot and ankle surgery by the American Board of Podiatric Surgery. He is in private practice in Phoenix. He is also a faculty member of the Podiatry Institute.

   Dr. Fishco pens a monthly blog for Podiatry Today. For more info, visit https://www.podiatrytoday.com/blogs/william-fishco-dpm-facfas .

   For further reading, see “When A Patient Presents With A Pruritic Lower Extremity Rash” in the April 2011 issue of Podiatry Today or “A Guide To Skin Conditions Of The Diabetic Foot” in the September 2004 issue.