When I worked as a Dermatologist at the Cleveland Clinic, we encountered many patients who were either referred by an outside Dermatologist, or self-referred, for a second opinion on their diagnosis or treatment or both. Most patients would bring copies of their records for us to review, and invariably, there would be skin biopsy results from one or more physicians. We would obtain a medical history and perform a complete skin examination of the patient, request the outside slides for consultation by our own Dermatopathologist, and perform additional diagnostic biopsies. There were times that I thought this might be overkill, for example, if the diagnosis seemed obvious from either the exam or the outside pathology reading. But whenever we accepted the diagnosis of the outside biopsy without reviewing the slide or made a new clinical diagnosis without repeating the biopsy, I noticed a higher probability of medical errors. Whenever my own patients seek a consultation at a major multi-specialty clinic such as the Mayo Clinic or MD Anderson, those institutions routinely request the original slides and perform their own biopsies. I think this is “good medicine.”
I would like to present 5 vignettes of cases that were referred to me by competent Dermatologists for second opinions. I believe these cases demonstrate the need for a complete reevaluation including re-biopsy when a second (or third or fourth, etc.) opinion is requested. In each case, the original diagnosis was first accepted and treatment was rendered accordingly. On subsequent follow-up visits, there was either no improvement, worsening, or progression of the disease, leading to additional tests and a different diagnosis.
Vignette #1. A woman in her 50’s was referred for scarring alopecia (hair loss) on the top of her scalp. She also complained of itching. The outside doctor had performed a scalp biopsy, and the interpretation of the pathologist was that of lichen planus of the hair follicle which is a well-known form of inflammation of the hair follicle that leads to hair loss and scarring. I treated her with a potent topical steroid solution which reduced the itching but did not stop progression of hair loss and scarring. I was now concerned about an infection of the hair follicles and requested permission to perform additional skin biopsies. Two biopsies demonstrated fungal filaments deep within the hair follicles confirming the diagnosis of Tinea capitis. I treated her with selenium sulfide shampoo to inactivate fungal spores on the surface and prevent spread of the infection and with oral Lamisil to kill the fungus living deep within the hair follicle. The condition was eventually cured and most of her hair grew back without any side-effects from the medication.
Comment. Our Dermatopathologist may have been able to find the fungus on the original outside biopsy with a special stain if I had requested the slide. Had I repeated the biopsy on the initial visit, I might have been able to change the diagnosis from lichen planus to Tinea capitis within days and prevent the delay in initiating the curative therapy.
Vignette #2. A man in his 30’s was referred for chronic hives called urticaria which were accompanied by fever with bone and joint pains. All of the features recurred periodically and were quite distressing and nearly disabling for him. Antihistamines did not help, but the rash was improved by the application of a potent topical steroid; the other symptoms were relieved by oral prednisone within a few weeks. Then the process started all over again.
A skin biopsy showed inflammation around small blood vessels in the skin including neutrophil white blood cells, suggesting the diagnosis of vasculitis. Further blood testing revealed abnormal circulating immunoglobulins (IgM) indicating that the diagnosis was a rare variant of urticaria called Schnitzler’s syndrome, one of the “auto-inflammatory periodic fever syndromes.” Some investigators believe it is a variant of urticarial vasculitis. A small percentage of patients go on to develop lymphoma or myeloma.
Comment. Schnitzler’s syndrome is difficult to diagnose and treat, but it has been reported to respond well to anakinra, an inhibitor of interleukin-1 as used in the treatment of rheumatoid arthritis. Other treatments are being studied.
Vignette #3. An elderly man was referred for the rapid development of warts on his arms and legs. Two skin biopsies had confirmed that diagnosis. Liquid nitrogen cryosurgery on several selected lesions was completely ineffective. Because it is unusual for adults to develop many warts in a short period of time, and because the bumps were mostly firm, waxy, and uniform in appearance, a different diagnosis was suspected. The original biopsies had been superficial in nature, therefore, the repeat biopsies were performed with a deep “punch” instrument. All 3 new biopsies from the arm and leg confirmed the new diagnosis scleromyxedema.
Scleromyxedema is a rare disease also called papular mucinosis because the numerous bumps contain deposits of mucin, an acid mucopolysaccharide, in the dermis that can be identified easily by special staining of the skin biopsy specimens. There is also increased deposition of collagen and fibroblasts, the cells that synthesize collagen. All of these features impart the shiny, firm, almost wood-like texture to the skin. Scleromyxedema must be differentiated from scleroderma which is a separate entity. Scleromyxedema almost always shows an abnormal immunoglobulin antibody (IgG) in the blood. There may be internal manifestations including muscle weakness, peripheral neuropathy, and kidney disease. A small number of patients go on to develop multiple myeloma.
Comment. Scleromyxedema is also very difficult to treat. Many different drugs have been tried: prednisone, melphalan, chlorambucil, cyclophosphamide, and thalidomide. More recently, stem cell transplants and intravenous immunoglobulins (IVIG) have been advocated. Spontaneous improvement has been described as long as 15 years after the onset.
Vignette #4. A middle-aged woman had seen 2 other Dermatologists for an annoying itchy rash predominantly on the trunk for months which consisted of small reddish-brown bumps, most of which had been scratched by the patient. Two previous biopsies reported features consistent with either eczema or Grover’s disease, and she was being treated with topical steroids with some benefit. The clinical exam did fit with these results, but the diagnosis was not specific. I treated the patient with a long-acting Kenalog (steroid) injection to reduce the itching. On the follow-up visit, the itching was improved, but there were still many small bumps, some linear, on the back, shoulders and chest. I performed additional biopsies which now clearly showed evidence of scabies infestation. She and her family were appropriately treated with good results.
I have discussed scabies mite infestation elsewhere on this blog where I personally confused it with poison ivy dermatitis. The itching caused by scabies is caused mostly by an allergic reaction to the mites, eggs, and feces in the skin rather than by their movements or chewing. Therefore, the itching is reduced to a great extent by the steroids.
Comment. Unfortunately, the steroids only temporarily mask the infestation and allow it to persist and possibly spread to others. Curative treatment requires general application of a miticide such as 5% permethrin to the skin of all household members, or an oral parasiticide such as ivermectin in resistant cases.
Vignette #5. An elderly woman consulted me for an exquisitely itchy generalized rash of several months’ duration. The rash was red, scaly, crusted, and scratched on the surface. She was in good general health, and no new medications had been started. Her previous Dermatologist had first treated her for scabies, the permethrin cream irritated her skin. He then performed skin biopsies which suggested the diagnosis of eczema or an allergic dermatitis. She was treated with topical steroids, but these either did not help or worsened her condition, according to her history.
I performed additional punch biopsies of the rash and adjacent normal-appearing skin. The first biopsy specimen was processed in the routine fashion while the second was submitted for direct immunofluorescence testing (DIF). The latter test screens for autoimmune diseases that show deposits of antibodies called immunoglobulins in the skin. In this case the DIF demonstrated IgA in the second layer of skin known as the papillary dermis, a finding which is diagnostic for Dermatitis herpetiformis. She has responded favorably to a combination of a strict gluten-free diet and the oral drug Dapsone.
Comment. Please read my blog on Dermatitis herpetiformis for more details on this interesting rare disease caused by hypersensitivity to wheat protein.
Bottom line: a second opinion, thoroughly done by an expert consultant, is a win-win situation in my view. It will either confirm that the first opinion is correct and reassure the patient and doctor to stay the course, or it will modify the first diagnosis or treatment and ultimately help the patient in the process. I welcome the second opinion in both directions, receiving it and rendering it.
Other Interesting Case Studies:
Psoriasis Associated with Plaquenil (Hydroxychloroquine)